BINOCULAR RIVALRY AND VISUOSPATIAL ABILITY IN INDIVIDUALS WITH SCHIZOPHRENIA
Karen R. Heslop
Bachelor of Nursing
Graduate Diploma (Social Science – Counselling)
Master of Education (Adult and Workplace)
A Thesis submitted as fulfilment for Degree of Doctor of Philosophy
School of Psychology and Counselling
Institute of Health and Biomedical Innovation
Queensland University of Technology
2012
Keywords
A1 allele, backward masking, Benton’s Judgment of Line Orientation, binocular rivalry, dopamine, schizophrenia, Taq1A
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Abstract
Visual abnormalities, both at the sensory input and the higher interpretive levels, have been associated with many of the symptoms of schizophrenia.
Individuals with schizophrenia typically experience distortions of sensory perception, resulting in perceptual hallucinations and delusions that are related to the observed visual deficits. Disorganised speech, thinking and behaviour are commonly experienced by sufferers of the disorder, and have also been attributed to perceptual disturbances associated with anomalies in visual processing. Compounding these issues are marked deficits in cognitive functioning that are observed in approximately 80% of those with schizophrenia. Cognitive impairments associated with schizophrenia include: difficulty with concentration and memory (i.e. working, visual and verbal), an impaired ability to process complex information, response inhibition and deficits in speed of processing, visual and verbal learning. Deficits in sustained attention or vigilance, poor executive functioning such as poor reasoning, problem solving, and social cognition, are all influenced by impaired visual processing. These symptoms impact on the internal perceptual world of those with schizophrenia, and hamper their ability to navigate their external environment.
Visual processing abnormalities in schizophrenia are likely to worsen personal, social and occupational functioning.
Binocular rivalry provides a unique opportunity to investigate the processes involved in visual awareness and visual perception. Binocular rivalry is the alternation of perceptual images that occurs when conflicting visual stimuli are presented to each eye in the same retinal location. The observer perceives the opposing images in an alternating fashion, despite the sensory input to each eye remaining constant. Binocular rivalry tasks have been developed to investigate
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specific parts of the visual system. The research presented in this Thesis provides an explorative investigation into binocular rivalry in schizophrenia, using the method of
Pettigrew and Miller (1998) and comparing individuals with schizophrenia to healthy controls. This method allows manipulations to the spatial and temporal frequency, luminance contrast and chromaticity of the visual stimuli. Manipulations to the rival stimuli affect the rate of binocular rivalry alternations and the time spent perceiving each image (dominance duration). Binocular rivalry rate and dominance durations provide useful measures to investigate aspects of visual neural processing that lead to the perceptual disturbances and cognitive dysfunction attributed to schizophrenia.
However, despite this promise the binocular rivalry phenomenon has not been extensively explored in schizophrenia to date.
Following a review of the literature, the research in this Thesis examined individual variation in binocular rivalry. The initial study (Chapter 2) explored the effect of systematically altering the properties of the stimuli (i.e. spatial and temporal frequency, luminance contrast and chromaticity) on binocular rivalry rate and dominance durations in healthy individuals (n=20). The findings showed that altering the stimuli with respect to temporal frequency and luminance contrast significantly affected rate. This is significant as processing of temporal frequency and luminance contrast have consistently been demonstrated to be abnormal in schizophrenia.
The current research then explored binocular rivalry in schizophrenia. The primary research question was, “Are binocular rivalry rates and dominance durations recorded in participants with schizophrenia different to those of the controls?” In this second study binocular rivalry data that were collected using low- and high- strength binocular rivalry were compared to alternations recorded during a monocular rivalry task, the Necker Cube task to replicate and advance the work of
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Miller et al., (2003). Participants with schizophrenia (n=20) recorded fewer alternations (i.e. slower alternation rates) than control participants (n=20) on both binocular rivalry tasks, however no difference was observed between the groups on the Necker cube task.
Magnocellular and parvocellular visual pathways, thought to be abnormal in schizophrenia, were also investigated in binocular rivalry. The binocular rivalry stimuli used in this third study (Chapter 4) were altered to bias the task for one of these two pathways. Participants with schizophrenia recorded slower binocular rivalry rates than controls in both binocular rivalry tasks. Using a ‘within subject design’, binocular rivalry data were compared to data collected from a backward- masking task widely accepted to bias both these pathways. Based on these data, a model of binocular rivalry, based on the magnocellular and parvocellular pathways that contribute to the dorsal and ventral visual streams, was developed.
Binocular rivalry rates were compared with performance on the Benton’s
Judgment of Line Orientation task, in individuals with schizophrenia compared to healthy controls (Chapter 5). The Benton’s Judgment of Line Orientation task is widely accepted to be processed within the right cerebral hemisphere, making it an appropriate task to investigate the role of the cerebral hemispheres in binocular rivalry, and to investigate the inter-hemispheric switching hypothesis of binocular rivalry proposed by Pettigrew and Miller (1998, 2003). The data were suggestive of intra-hemispheric rather than an inter-hemispheric visual processing in binocular rivalry.
Neurotransmitter involvement in binocular rivalry, backward masking and
Judgment of Line Orientation in schizophrenia were investigated using a genetic indicator of dopamine receptor distribution and functioning; the presence of the Taq1
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allele of the dopamine D2 receptor (DRD2) receptor gene. This final study (Chapter
6) explored whether the presence of the Taq1 allele of the DRD2 receptor gene, and thus, by inference the distribution of dopamine receptors and dopamine function, accounted for the large individual variation in binocular rivalry. The presence of the
Taq1 allele was associated with slower binocular rivalry rates or poorer performance in the backward masking and Judgment of Line Orientation tasks seen in the group with schizophrenia.
This Thesis has contributed to what is known about binocular rivalry in schizophrenia. Consistently slower binocular rivalry rates were observed in participants with schizophrenia, indicating abnormally-slow visual processing in this group. These data support previous studies reporting visual processing abnormalities in schizophrenia and suggest that a slow binocular rivalry rate is not a feature specific to bipolar disorder, but may be a feature of disorders with psychotic features generally.
The contributions of the magnocellular or dorsal pathways and parvocellular or
ventral pathways to binocular rivalry, and therefore to perceptual awareness, were
investigated. The data presented supported the view that the magnocellular system initiates perceptual awareness of an image and the parvocellular system maintains the
perception of the image, making it available to higher level processing occurring
within the cortical hemispheres. Abnormal magnocellular and parvocellular processing may both contribute to perceptual disturbances that ultimately contribute to the cognitive dysfunction associated with schizophrenia. An alternative model of
binocular rivalry based on these observations was proposed.
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Table of Contents
Keywords ...... i Abstract ...... ii List of Figures ...... xii List of Tables ...... xiv List of Abbreviations ...... xvi Statement of Original Authorship ...... xix Acknowledgments ...... xx CHAPTER 1: Literature Review - Visual Processing In Schizophrenia and Binocular Rivalry ...... 1 1.1 Schizophrenia ...... 1 1.2 Perceptual Disturbances in Schizophrenia ...... 3 1.3 Delusional Experiences ...... 4 1.3.1 Disorganised thoughts and behaviour...... 5 1.4 Cognitive Deficits in Schizophrenia ...... 6 1.4.1 Visual-evoked potentials in schizophrenia...... 7 1.4.2 Functional magnetic resonance imaging Studies (fMRI) in schizophrenia...... 10 1.4.3 Magnocellular and parvocellular visual pathways in schizophrenia...... 12 1.4.4 The cerebral hemispheres and schizophrenia...... 14 1.4.5 Neurotransmitters in schizophrenia...... 14 1.4.6 Dopamine genes in schizophrenia...... 16 1.4.7 Perceptual rivalry in schizophrenia...... 17 1.4.8 Binocular rivalry in schizophrenia...... 19 1.5 Binocular Rivalry ...... 22 1.5.1 Stimulus parameters moderate binocular rivalry ...... 24 1.5.1.1 Spatial frequency...... 25 1.5.1.2 Movement...... 26 1.5.1.3 Luminance...... 26 1.5.1.4 Colour...... 27 1.5.1.5 Orientation...... 27 1.5.1.6 Size...... 28 1.5.1.7 Context...... 28 1.6 Theories of Binocular Rivalry ...... 28 1.6.1 Bottom-up theories of binocular rivalry...... 29 1.6.2 Visual-evoked potentials (VEPs) in binocular rivalry ...... 31 1.7 Top- down Theories of Binocular Rivalry ...... 32 1.7.1 Single-cell studies...... 33 1.7.2 Imaging studies...... 33 1.7.3 Eye-swapping methodologies...... 34 1.7.4 Neurotransmitter involvement in binocular rivalry...... 35 1.7.5 Monocular rivalry compared to binocular rivalry...... 36
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1.8 Multi-level or Hierarchical Theories ...... 36 1.8.1 Visual pathway theories of binocular rivalry ...... 37 1.8.1.1 Monocular and binocular pathways...... 37 1.8.1.2 Magnocellular and parvocellular pathways...... 38 1.8.2 Inter-hemispheric theory of binocular rivalry...... 39 1.9 Summary and introduction to Chapters ...... 41 CHAPTER 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry .. 49 2.1 Binocular rivalry ...... 49 2.1.1 Binocular rivalry rate...... 49 2.1.2 Dominance durations...... 52 2.2 Study 1 ...... 53 2.2.1 Aims...... 53 2.2.2 Hypotheses...... 53 2.3 Method ...... 54 2.3.1 Participants...... 54 2.3.2 Apparatus...... 55 2.3.2.1 Binocular rivalry stimuli...... 55 2.4 Design ...... 58 2.5 Procedure ...... 59 2.6 Statistical Analyses ...... 60 2.6.1 Two-sided Smirnov test to compare dominance duration distributions...... 60 2.7 Results ...... 61 2.7.1 Binocular rivalry rate...... 61 2.7.2 Fast versus slow alternators (binocular rivalry rate)...... 64 2.7.3 Binocular rivalry dominance durations in fast and slow alternators...... 68 2.8 Discussion ...... 72 2.8.1 Binocular rivalry rates...... 72 2.8.2 Dominance durations...... 76 2.8.3 Age...... 78 2.9 Conclusion ...... 78 CHAPTER 3: Slower Binocular Rivalry Rates in Individuals with Schizophrenia Compared to Healthy Controls ...... 81 3.1 Binocular Rivalry Rate in Major Psychiatric Illness ...... 81 3.2 Study 2 ...... 85 3.2.1 Aims...... 85 3.2.2 Hypotheses...... 86 3.3 Method ...... 86 3.3.1 Participants...... 86 3.3.1.1 Healthy participants...... 87 3.3.1.2 Participants with schizophrenia...... 87 3.3.1.3 Procedure ...... 89
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3.3.1.3.1 BINOCULAR RIVALRY TESTING...... 89
3.3.1.3.2 PERCEPTUAL RIVALRY TESTING; THE NECKER CUBE...... 90 3.4 Statistical Analyses ...... 91 3.5 Results ...... 93 3.5.1 Binocular rivalry rate...... 93 3.5.2 Necker Cube alternation rates...... 94 3.5.3 Normalised mean dominance durations...... 96 3.6 Discussion ...... 97 3.6.1 Binocular rivalry rates in schizophrenia...... 99 3.6.2 Monocular rivalry rates in schizophrenia...... 100 3.6.3 Distributions, gamma plots...... 101 3.6.4 Effect of stimulus strength...... 102 3.6.5 Diagnostic value of binocular rivalry rate...... 103 3.6.6 Physiological mechanisms for the slowing of binocular rivalry rate. ... 104 3.6.7 Effect of schizophrenia medication dose...... 105 3.7 Conclusion ...... 106 CHAPTER 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway- Specific Abnormalities in Schizophrenia ...... 108 4.1 Magnocellular and Parvocellular Pathways in Schizophrenia ...... 108 4.1.1 Physiological differences in the magnocellular and parvocellular pathways...... 110 4.1.2 Magnocellular and parvocellular pathways in binocular rivalry...... 112 4.2 Study 3, Experiment 1: Assessing Binocular Rivalry in Schizophrenia Using Stimuli that Bias the Magnocellular and Parvocellular Visual Pathways ...... 114 4.2.1 Method...... 115 4.2.1.1 Participants with schizophrenia...... 115 4.2.1.2 Control participants...... 115 4.2.1.3 Binocular rivalry stimuli to bias the magnocellular and parvocellular pathways...... 116 4.2.1.4 Recording binocular rivalry...... 117 4.2.2 Statistical analyses...... 117 4.2.3 Results...... 118 4.2.3.1 Binocular rivalry rate...... 118 4.2.3.2 Dominance intervals...... 121 4.2.4 Discussion related to magnocellular and parvocellular tasks...... 122 4.2.4.1 Binocular rivalry rates...... 122 4.2.4.2 Dominance duration intervals...... 123 4.2.4.3 Gender differences...... 127 4.3 A Backward-Masking Task Utilising Stimuli that Bias the Magnocellular and Parvocellular Visual Pathways ...... 129 4.3.1 Introduction...... 129 4.3.1.1 Comparing binocular rivalry with other neurophysical tasks. 129 4.3.1.2 Development of the visual backward masking task...... 131 4.3.1.3 The visual backward masking task procedure...... 133 4.3.1.4 Results of preliminary testing...... 134
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4.4 Experiment 2: Comparing Visual Backward Masking and Binocular Rivalry Tasks to Investigate Magnocellular and Parvocellular Processes...... 136 4.4.1 Methods...... 136 4.4.1.1 Schizophrenia participants...... 136 4.4.1.2 Healthy controls...... 137 4.4.2.2 Binocular rivalry and visual backward masking stimuli...... 137 4.4.2 Statistical analyses...... 138 4.4.3 Results...... 138 4.4.3.1 Binocular rivalry rates...... 138 4.4.3.2 Dominance intervals...... 140 4.4.3.3 Visual backward masking (VBM)...... 141 4.4.3.4 Comparing binocular rivalry and visual backward masking results...... 145 4.4.4 Discussion relating to visual backward masking...... 147 4.5 General Discussion ...... 150 4.5.1 A model of binocular rivalry based on visual backward masking theory...... 154 4.6 Conclusion ...... 159 CHAPTER 5: Benton’s Judgment Of Line Orientation - An Indicator of Visuospatial Ability In Schizophrenia ...... 161 5.1 The Right Hemisphere and Visuospatial Dysfunction ...... 161 5.2 The Benton’s Judgment of Line Orientation Task ...... 163 5.2.1 Scoring the Benton’s Judgment of Line Orientation task...... 164 5.2.1.1 Global score...... 164 5.2.1.2 Error type...... 166 5.2.1.3 Individual line errors...... 167 5.2.1.4 Hemi-space errors...... 167 5.3 Pilot Testing the Computer Version of BJLO and Alternative Scoring Systems168 5.3.1 Method...... 170 5.3.1.1 Participants...... 170 5.3.1.2 Procedure...... 170 5.3.2 Results of pilot test ...... 171 5.4 Study 4, Benton’s Judgment of Line Orientation in Participants with Schizophrenia ...... 172 5.4.1 Aims...... 172 5.4.2 Method...... 173 5.4.2.1 Participants with schizophrenia...... 173 5.4.2.2 Healthy control participants...... 173 5.4.2.3 Procedures...... 173 5.4.3 Statistical analyses...... 174 5.4.4 Results...... 175 5.4.5.1 Global score analysis...... 175 5.4.5.2 Error type analysis...... 176 5.5.5.3 Line error analysis...... 176 5.5.5.4 Hemi-space analyses...... 177 5.5 Association between Benton’s Judgment of Line Orientation and binocular rivalry ...... 177
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5.6. Global score ...... 178 5.7.1.1 Error type...... 182 5.7.1.2 Hemi-space...... 183 5.7.2 Potential Impact of BJLO Performance ...... 184 5.7.2.1 Age and gender...... 184 5.7.2.2. Medication effects...... 184 5.7.2.3 Schizophrenia sub-types and symptom ratings...... 184 5.7.2.4 Cognitive ability...... 185 5.7.3 Comparing Benton’s Judgment of Line Orientation with Binocular Rivalry ...... 185 5.7.4 Cortical Pathway and Hemispheric Models of Involvement ...... 186 5.7.4.1 Dorsal and Ventral Pathways ...... 186 5.7.4.2 The Cortical Hemispheres ...... 187 5.6 Conclusion ...... 188 CHAPTER 6: Taq1 Allele of the DRD2 Dopamine Receptor Gene, Binocular Rivalry, Visual Backward Masking and Benton’s Judgment of Line Orientation ... 190 6.1 Dopamine in Vision ...... 190 6.1.1 The A1 allele of the DRD2 receptor gene...... 191 6.1.2 The A1 allele of the DRD2 receptor in vision...... 194 6.2 Aims ...... 195 6.3 Method ...... 195 6.3.1 DNA collection and extraction...... 195 6.3.2 Participants...... 196 6.3.2.1 Control participants who participated in the binocular rivalry tasks in Study 1...... 197 6.3.2.2 Participants with schizophrenia and healthy controls who participated in binocular rivalry, Studies 2 and 3 and the Necker Cube task in Study 2 (Chapters 3 and 4)...... 197 6.3.2.3 Participants with schizophrenia and healthy controls who participated in visual backward masking tasks in Study 3 (Chapter 4).198 6.3.2.4 Participants with schizophrenia and healthy controls who participated in Benton’s Judgment of Line Orientation in Study 4 (Chapter 5)...... 198 6.4 Results ...... 199 6.4.1 Binocular rivalry results...... 199 6.4.1.1 Binocular rivalry in control participants in 16 stimulus Conditions from Study 1...... 199 6.4.1.2 Binocular rivalry rates in low- and high-strength, magnocellular and parvocellular biased binocular rivalry tasks and the Necker cube.200 6.4.3 Benton’s Judgment of Line Orientation Task results...... 200 6.5 Discussion ...... 204 CHAPTER 7: Overview, General Discussion and Conclusions ...... 209 7.1 Overview and General Discussion ...... 209 7.1.1 Exploring binocular rivalry rate...... 209 7.1.2 Dominance durations...... 210 7.2 Neurotransmission and Binocular Rivalry: Does Dopamine Have a Role? ... 212
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7.3 Combining Theories to Produce a New Model of Binocular Rivalry ...... 213 7.4 Slower Binocular Rivalry and Visual Processing in Schizophrenia ...... 216 7.5 Limitations ...... 217 7.6 Implications for Future Research ...... 223 7.7 Conclusion ...... 225 REFERENCES ...... 228
APPENDICES……………………………………………………………………..296
Appendix A: Backward Masking Task Instructions for Parvocellular VBM Task………………………………………………………………………………..296 Appendix B: Backward Masking Task Instructions for Magnocellular Visual Backward Masking (VBM) Task ...... 298 Appendix C: Effect of Schizophrenia Characteristics on Visual Backward Masking (VBM) Tasks ...... 300 Appendix D: Score Sheet - Benton’s Judgment of Line Orientation (BJLO) ...... 302 Appendix E. Benton Judgment of Line Orientation (BJLO) Performance Scores in Participants with Schizophrenia and Healthy Controls by A1 Allele of the DRD2 Receptor Gene...... 304
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List of Figures
Figure 2.1: Binocular rivalry rates by 20 participants across all stimulus conditions (n = 16)...... 62
Figure 2.2: Mean binocular rivalry rates (n = 20) across the 16 stimulus conditions...... 63
Figure 2.3: The effect of increasing stimulus strength on binocular rivalry rate in ‘slow’ and ‘fast’ alternators: binocular rivalry rates recorded by 20 healthy volunteers grouped based on the participants mean binocular rivalry alternation rate, A. The effect of increasing stimulus strength by introducing movement to low and high luminance stimuli in fast (n=3) and slow (n=3) alternators. B...... 67
Figure 2.4: The effect of stimulus strength on binocular rivalry rate: Binocular rivalry rate increases as stimulus strength increases...... 68
Figure 2.5:Cumulative frequency distributions of normalized dominance durations recorded by fast alternators (n = 3) compared with slow alternators (n = 3) in 16 stimulus conditions...... 72
Figure 3.1: Mean alternation rates recorded in schizophrenia participants (n = 20, grey diamonds) compared healthy controls (n = 20, black squares) in two binocular rivalry tasks...... 95
Figure 3.2: Normalised mean dominance durations (the time intervals between button pushes (in seconds)/mean) plotted as cumulative distributions...... 98
Figure 4.1:Binocular rivalry rates recorded in participants with schizophrenia (black triangles) compared to healthy controls (black diamonds)...... 120
Figure 4.2: Difference between the dominance durations of participants with schizophrenia (black lines) and healthy control participants (grey lines) for (A) the magnocellular binocular rivalry (BR) task and (B) the parvocellular BR task...... 124 Figure 4.3: Binocular rivalry (BR) rates recorded in participants with schizophrenia (black triangles) compared to healthy controls (black diamonds)...... 140
Figure 4.4: The dominance durations between participants with schizophrenia (black lines) compared to healthy participants (grey lines) for (A) magnocellular binocular rivalry (BR) task and (b) parvocellular BR task...... 143
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Figure 4.5: Number of correct responses as a function of inter-stimulus interval in healthy controls and participants with schizophrenia for (A) magnocellular visual backward-masking(VBM) and (B) parvocellular VBM tasks...... 144
Figure 4.6: The hypothesised time course of activation of transient and sustained channels after a brief presentation of a stimulus...... 151
Figure 4.7: The time course of the transient and sustained channels when the target precedes the mask (backward masking)...... 152
Figure 4.8: Transient (magnocellular) neurons inhibit sustained ones via internuncial neurons at the lateral geniculate nucleus (LGN) and cortex. The impulse response by the internuncial neuron is initiatory at the postsynaptic potential and integrates with the sustained neuron at either the LGN or cortex...... 155
Figure 4.9: A revised model of binocular rivalry with rapid magnocellular response followed by the parvocellular response to continuous stimuli (vertical and horizontal lines) in the right and left eyes respectively at corresponding retinotopic areas...... 158
Figure 5.1: An item from the Benton’s Judgement of Line Orientation (BJLO) task...... 165
Figure 6.1: Benton’s Judgement of Line Orientation (BJLO) line error scores according to the presence of the A1 allele in subjects with (a) schizophrenia and (b) healthy controls...... 206
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List of Tables
Table 2.1: The Kolmogorov-Smirnov goodness of fit analysis statistics for the dominance duration distributions for fast and slow alternators over 16 stimulus conditions (n=20)...... 70
Table 2.2: The two-sided Smirnov test statistic for fast and slow alternators (m and n respectively) compared with the critical values determined by of T1 at the 0.95 quantile (w0.95 ≈1.36√ m+n/ mn) across the 16 test binocular rivalry stimuli conditions (n=20)...... 71
Table 3.1: Age, gender, eye dominance and NART scores of controls and participants with schizophrenia ...... 88
Table 3.2: Smirnov test statistic for participants with schizophrenia (n=20) and controls (n=20)...... 97
Table 4.1: Age, gender, eye dominance and NART score of participants with schizophrenia and controls ...... 116
Table 4.2: Smirnov test results indicating differences in the distribution of dominance durations between participants with schizophrenia (n=17) and controls (n=24) for both magnocellular and parvocellular binocular rivalry (BR) tasks...... 121
Table 4.3: Correct target letter identification by location and letter in a preliminary test of the magnocellular and parvocellular visual backward masking (VBM) task (n = 5)...... 135
Table 4.4: Age, gender, eye dominance and NART score of controls and participants with schizophrenia...... 137
Table 4.5: Differences in the distribution of dominance durations between participants with schizophrenia and controls in magnocellular and parvocellular binocular rivalry (BR) tasks: Smirnov test outcomes of dominance duration distributions...... 141
Table 4.6: Differences in correct identification of a target scores in magnocellular and parvocellular visual backward- masking (VBM) tasks between participants with schizophrenia and healthy controls at four inter-stimulus intervals (ISI) ...... 142
Table 4.7: Correlations between magnocellular and parvocellular binocular rivalry (BR) rates (in Hz) with magnocellular and parvocellular visual backward masking (VBM) correct scores (Spearman’s correlation coefficient rho)...... 146
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Table 5.1: Method of analysing Benton’s Line of Judgement Orientation (BJLO) results as per (Ska ...... 169
Table 5.2: Age, gender, eye dominance and NART score of participants with schizophrenia and Controls...... 174
Table 5.3: Benton’s Judgement of Line Orientation (BJLO) data for control participants and participants with schizophrenia: mean global scores (out of 30 and 60), line error scores and hemi-space errors for the BJLO task...... 179
Table 5.4: Benton’s Judgement of Line Orientation (BJLO) data for healthy control participants and participants with schizophrenia: error type in the BJLO task ...... 180
Table 5.5: Correlations between global Benton’s Judgement of Line Orientation (BJLO) scores and binocular rivalry (BR) rates for stimuli that bias the BR task for either the magnocellular or parvocellular visual pathways (spearman rank order)...... 181
Table 6.1: Demographic characteristics of participants genotyped for the presence of the Taq1 A DRD2 alleles receptor for studies 2, 3 and 4...... 199
Table 6.2: Binocular rivalry rates recorded by A1+ healthy participants (n = 5) compared A1- healthy participants (n = 11) over the 16 stimulus conditions...... 201
Table 6.3: Binocular rivalry rates recorded by A1+ and A1- participants using binocular rivalry tasks with high and low strength stimuli, magnocellular and parvocellular biased stimuli and the Necker Cube ...... 202
Table 6.4: Correct scores in backward masking tasks that bias magnocellular and parvocellular visual pathways at 4 inter-stimulus intervals (ISI) recorded by A1+ and A1- participants with schizophrenia...... 206
Table 6.5: Correct scores in backward masking tasks that bias magnocellular and parvocellular visual pathways at 4 inter-stimulus intervals (ISI) recorded by A1+ and A1- control participants ...... 205
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List of Abbreviations
A1+ Positive for the presence of the A1 allele of the DRD2 receptor gene
A1- Negative for the presence of the A1 allele of the DRD2 receptor gene
BJLO Benton’s Judgement of Line Orientation
BOLD Blood-oxygenation level dependent bp Base pairs
BPD Bipolar Disorder
BPRS Brief Psychiatric Rating Scale
BR Binocular Rivalry c/d Cycles per degree
COMT Catechol-O-methyl transferase
CNTRICS Cognitive Neuroscience Treatment Research to Improve Cognition in
Schizophrenia cpd Cycles per degree of visual angle c/s Cycles per second
CPZE Chlorpromazine equivalents deg Degrees dLGN Dorsal Lateral Geniculate Nucleus
DSM-IV Diagnostic and Statistical Manual of Mental Disorders – Edition 4
DRD2 Dopamine D2 receptor
DSA Dichoptic stimulus alternation
EEG Electroencephalography
ERP Event related potential fMRI Functional Magnetic Resonance Imaging
GABA Gamma-Aminobutyric acid
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H Horizontal
Hz Hertz
ISI Inter-stimulus interval
LGN Lateral Geniculate Nucleus msec Milliseconds
MEG Magnetoencephalography
MRI Medical resonance imaging
MT Middle Temporal visual area (also referred to as V5)
N Negative
NART National Adult Reading Test
NMDA N-methyl-D-aspartic acid
PANSS Positive and Negative Schizophrenia Syndrome scale
P Positive
PET Positron emission tomography
PTSD Post-traumatic stress disorder
SCID Structured Clinical Interview for DSM-IV
Sec Seconds t-VEP Transient visual-evoked potential
VBM Visual Backward Masking
VEP Visual Evoked Potential
V1 Visual area 1, the extra striate cortex (also known as the primary
visual pathway)
V2 Visual area 2, the pre-striate cortex
V3 Visual area 3
V4 Visual area 4
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V5 Visual area 5 (also known as the middle temporal visual area)
5-HT Serotonin
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Statement of Original Authorship
The work contained in this Thesis has not been previously submitted to meet requirements for an award at this or any other higher education institution. To the best of my knowledge and belief, the Thesis contains no material previously published or written by another person, except where due reference is made.
Name: Karen Ruth Heslop
Signature: …………………..
Dated: …………………..
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Acknowledgments
I would like to acknowledge the support, guidance, scholarly advice and encouragement offered by Professor Ross Young and Associate Professor and
Katrina Schmid. I also wish to thank them both for providing practical support and the many hours they spent reviewing my written work and providing constructive feedback that helped with the direction of the project.
I would also like thank Dr Bruce Lawford for his infectious enthusiasm for genetics, schizophrenia and research, and Dr Simon Burton for his clinical insights, moral support and his assistance in developing many of the tasks.
Thank you also to the individuals who participated in this research as part of the clinical group, and to my friends, colleagues and fellow students who acted as controls and spent many hours in dimly-lit rooms, wearing strange goggles and pushing buttons on a computer keyboard in response to some lines on a screen.
I wish to also thank Dr Steven Miller, Dr Guang Bin Lui and Professor Jack
Pettigrew whose work initially inspired me to investigate this fascinating phenomenon, and for making the binocular rivalry task available to me. Thank you also to Professor Stan Catts and Professor Laurie Geffen for their valued contributions early in the project, and to Associate Professor Jason O’Connor and Dr
Cameron Hurst for their statistical advice.
Most of all I wish to thank Brett for his continued support and patience.
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Chapter 1: Literature Review - Visual Processing in Schizophrenia and Binocular
Rivalry
1.1 Schizophrenia
Schizophrenia is a complex brain disorder characterised by cognitive dysfunction that causes long-term disability, altered sensory perception, dysregulation of emotion and disturbed behaviour (Brenner, Krishnan, Vohs, Ahn,
Hetrick & Morzorati, 2009). Despite many years of research into the disorder spanning the disciplines of the physical, psychological and neurological sciences, genetic and epidemiological research, there is no one theory that satisfactorily explains the symptoms or pathophysiology of schizophrenia. While advances in the field of neurosciences, and brain imaging have provided key insights into this disorder many fundamental questions remain unanswered.
It is generally agreed that sufferers experience both subjective sensory anomalies and objective deficits of sensory function (Brenner et al., 2009) that contribute to many of the symptoms of schizophrenia. Symptoms of schizophrenia include visual, auditory and olfactory hallucinations associated with distortions of sensory perception (Andreasen, Arndt, Alliger, Miller & Flaum, 1995; Butler,
Silverstein & Dakin, 2008) and delusions or firmly-held false beliefs that result from mis-interpretations of these perceptions and personal experiences (Frith, & Dolan,
1997). Sufferers may also experience disorganised speech, thinking and behaviour, agitation, social dis-inhibition and bizarre behaviours (Andreasen et al., 1995).
Many individuals with schizophrenia experience a reduced intensity range of emotional expression (affective flattening), poverty of speech (alogia), a reduction or inability to initiate and maintain goal-directed behaviour (avolition) and a marked decrease in reaction to the immediate surrounding environment (Cadenhead, Geyer,
Literature Review - Visual Processing in Schizophrenia and Binocular Rivalry 1
Butler, Perry, Sprock & Braff, 1997; Uhlhaas, Phillips & Silverstein, 2005). The symptoms of schizophrenia impact on the individuals’ internal world and hamper their ability to navigate their external environments and impair their overall functioning (Couture, Granholm & Fish, 2010). Therefore, individuals with schizophrenia experience poorer social and occupational functioning compared to their unaffected peers (Peuskens, Demily & Thibaut, 2005; Tan, 2009; Tsang, Leung,
Chung, Bell & Cheung, 2010).
Compounding these issues are marked deficits in cognitive functioning.
Cognitive impairment is considered a core feature of schizophrenia, with more than
80% of patients showing significant impairment (Bora, Yucel & Pantelis, 2010).
Cognitive deficits associated with schizophrenia include: difficulty with concentration and memory (i.e. working, visual and verbal), the limited ability to process complex information, response inhibition, and deficits in speed of processing, visual and verbal learning. Those with schizophrenia also experience difficulty with sustained attention or vigilance, and difficulties in executive function such as reasoning, problem solving and social cognition (Bora, Yucel, & Pantelis,
2010; Green, 2006; Tomás, Fuentes, Roder & Ruiz, 2010).
Researchers investigating visual abnormalities in schizophrenia, that are known to contribute to cognitive deficits and perceptual disturbance characteristic of the disorder, generally subscribe to either “top-down” or “bottom-up” theories (see
Butler, Silverstein & Dakin, 2008; Javitt, 2009; Piskulic, Oliver, Norman & Maruff,
2007, for reviews). Traditionally, the perceptual visual disturbances in schizophrenia have been viewed as being consequential to “top-down” processing (Frith & Dolan,
1997; Gilbert & Sigman 2007; Grossberg, 2000; Kveraga, Ghuman & Bar, 2007;
Laycock, Crewther & Crewther, 2007) where disturbances in localised cortical
2 Literature Review - Visual Processing in Schizophrenia and Binocular Rivalry
regions diminish cognitive processing, attention, memory and executive functioning and ultimately affect social functioning and outcomes (Javitt, 2009). However, the focus in schizophrenia research has shifted toward perceptual disturbances, abnormalities early in the visual pathway, and their contributions to higher cognitive deficits (Bulter et al., 2005; Butler, Martinex, Foxe, Kim, Zemon, Silipo, Mahoney,
Shpaner, Jalbrzikowski & Javitt, 2007; Javitt, 2009; Martinez, Hillyard, Dias, Hagler,
Butler, Guilfoyle, Jalbrzikowski, Silipo & Jarvitt, 2008).
1.2 Perceptual Disturbances in Schizophrenia
Individuals with schizophrenia have marked deficits in detecting low-contrast visual stimuli (Keri, Antal, Szekeres, Benedek & Janka, 2000; Keri & Benedek,
2007), stimuli with low luminance and spatial frequencies, and stimuli presented at varying temporal speeds (or pulsing stimuli) (Chen, Levy, Matthysse, Holzman &
Nakayama, 2000; Keri, Antal, Benedek & Janka, 2000; Keri, Antal, Szekeres,
Benedek & Janka, 2000; Schwarts, McGinn & Winstead, 1987; Schwartz, Mallot &
Winstead, 1988; Slaghuis, 1998; Slaghuis & Bishop, 2001; Slaghuis & Thompson,
2003; Slaghuis, 2004). Such deficits in perception reduce the individual’s ability to identify salient visual information in day-to-day situations (Poirel, Brazo, Turbelin,
Lecardeur, Simon, Houde, Pineau & Dollfus, 2010). Damage to sensory processing areas, that allow prior knowledge of a sensory input to be related to random incoming sensory information (Frith & Dolan, 1997), may inhibit the correct identification of visual stimuli, resulting in sensory hallucinations. These perceptual disturbances involve aberrant cortical activations of networks at differing levels of complexity in the brain (Jardri, Pouchet, Pins & Thomas, 2010). Dysfunction in the posterior area of the brain that mediates visual perceptual processing (the primary visual cortex) has been implicated in object and visual spatial perceptions that are
Literature Review - Visual Processing in Schizophrenia and Binocular Rivalry 3
frequently noted in schizophrenia (Tek, Gold, Blaxton, Wilk, McMahon &
Buchanan, 2002). Prefrontal areas that are involved in maintaining information during short delay intervals between visual stimuli are also affected in schizophrenia
(Tek et al., 2002).
1.3 Delusional Experiences
Sensory gating abnormalities (i.e. the ability to ignore irrelevant information while focusing on a salient features) that are related to perceptual and attentional mechanisms, have been reported by individuals with schizophrenia (Hetrick,
Erickson & Smith, 2010). Poor sensory gating, together with a reduction in the quality of sensory input, results in a heightened awareness of background stimuli and poor selective attention. Therefore, individuals with schizophrenia often have difficulty correctly identifying the source of a perceptual stimulus, filtering out unimportant information and interpreting sensory perceptions to determine a context for the incoming stimuli. The individual may thus misinterpret sensory information; believing external forces are controlling their actions or thoughts, or thinking that they can control events that are not under their control (Voss, Moore, Hauser,
Gallinat, Heinz & Haggard, 2010). Failure to correctly make this distinction may account for the strong association between hallucinations and paranoid delusions in schizophrenia; the person with schizophrenia not only hears voices or misinterprets visual stimuli, but attributes (usually hostile) intentions to these voices and visual experiences (Frith & Dolan, 1997). Prior knowledge, or memory of sensory input, enables us to distinguish our own actions from those of independent agents in the outside world. Many theorists posit that delusional disturbances are related to a mis- match between predicted and actual sensory feedback that relies on an intact central comparator mechanism (Voss et al., 2010).
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The visual environment consists of global features (for example, a forest) and local features (for example a tree). Global visual information provides the context in which local information is interpreted. For example, a tree in a forest appears to be in context, while a tree in a kitchen of a house is considered out of context. It has been suggested that individuals with schizophrenia have difficulty processing global information and therefore context, and tend to focus more on local features (Poirel et al., 2010) therefore resulting in a local bias. This local bias leads to an incorrect interpretation of visual information.
1.3.1 Disorganised thoughts and behaviour.
Individuals with schizophrenia require greater delays between two temporally presented images in order to detect the two discrete images. When images are separated by only 90-150 millisecond (msec) intervals they tend to view temporally- modulated images as continuous presentations (Schwartz, Evans, Pena & Winstead,
1994). Tasks that require observers to identify a blank image (an inter-stimulus interval) between two sinusoidal gratings (Schwartz & Winstead, 1998; Schwartz, et al., 1994) or between two flashed stimuli consistently separate those with schizophrenia from healthy controls (Schwartz, Satter, O’Neill & Winstead, 1990;
Schwartz & Winstead, 1988; Schwartz, et al., 1994). These abnormally-long inter- stimulus intervals have been correlated with disorganised thoughts and behaviours in schizophrenia (Norton, Ongur, Stromeyer & Chen, 2008).
Furthermore, the visual motion pathway that includes a local and a global processing stage, each of which has distinct neural substrates, is disrupted in schizophrenia. In schizophrenia, global (but not local) processing stage of the visual motion system is compromised. These motion-sensitive brain areas are abnormal in schizophrenia. These areas possess large receptive fields for spatial and temporal
Literature Review - Visual Processing in Schizophrenia and Binocular Rivalry 5
integration, such as the middle temporal and medial superior temporal areas (Chen,
Nakayama, Levy, Matthysse & Holzman, 2003). These regions are integral for the detection of motion and spatial orientation, the shifting of attention and orientating oneself during self-movement (Duffy and Wurtz, 1997). Such abnormalities may manifest in schizophrenia as disorganised or slowed thinking, difficulty with understanding, expressing and integrating thoughts, feelings and behaviours. These deficits are generally thought to be related to deficits in the neural pathways that relate to the sequencing of information or timing of neural information flow
(Andreasen et al., 1995; Barrett, Mulholland, Cooper & Rushe, 2009; Couture,
Granholm & Fish, 2010).
1.4 Cognitive Deficits in Schizophrenia
Cognitive deficits are thought to be related to higher-order sensory deficits.
Current neurophysiological models suggest deficits in cognitive processing are due to impairments in basic perceptual processes that localise to primary sensory brain regions (Butler, Martinez, Foxe, Kim, Zemon, Silipo, Mahoney, Shpaner,
Jalbrzikowski & Javitt, 2007; Butler, Schechter, Zemon, Schwartz, Greenstein,
Gordon, Schroeder & Javitt, 2001; Javitt, 2009).
The ability to track visual information allows us to efficiently process and interpret incoming visual information which is essential for effective interaction with our external environment. In schizophrenia, abnormal eye tracking is hypothesised to be a fundamental component of the perceptual disturbance and abnormal cognitive processing associated with the disorder (Javitt, 2009). Eye tracking abnormalities have been observed in working memory (Levin et al; 1988; Park & Holzman, 1993;
Sereno & Holzman, 1995). These abnormalities have also been evident in cognitive processing tasks (Campanella & Guerit, 2009; Litman et al., 1991; Solomon,
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Holzman, Levin & Gale, 1997), contrast and velocity discrimination (Chen, Levy, et al., 1999) and motion detection (Chen, Nakayama, Levy Matthysse & Holzman,
2003) in schizophrenia. Importantly, they are independent of medication effects
(Grawe & Levander, 1995; Holzman, O’Brian & Waternaux, 1991; Litman et al.,
1989; Litman, Hommer, Radant, Clem & Pickar, 1994) and severity of illness
(Bartifai, Levander, Nyback, Berggren & Schalling, 1995). These abnormalities may reflect a failure of cortical and/or cerebellar function in areas coordinating saccadic and pursuit eye movements during visual tracking (Avila, Weiler, Lahti, Tamminga
& Thaker, 2002; Hong et al., 2005; O’Driscoll et al., 1998) or magnocellular deficits
(Laycock, Crewther & Crewther, 2008; Schwartz, Maron, Evans & Winstead, 1996b)
Cognitive deficits associated with schizophrenia are also likely to be related to abnormalities in the architecture or structure of the brain, or dysfunction in the structures or mechanisms associated with information processing. These include the neural pathways and neurotransmitters involved in visual processing. There have been many advances in the scientific investigation into visual processing that have provided new insights into schizophrenia. Investigations of brain function by measuring visual-evoked potentials, using functional magnetic resonance imaging
(fMRI) to investigate visual pathways and the cortical hemispheres have made a significant contribution over the recent decades. Investigations into the neurotransmitters and the genetic determinants of neurotransmission have also gathered momentum.
1.4.1 Visual-evoked potentials in schizophrenia.
A visual-evoked potential (VEP) is an electrical potential (forming either positive [P] or negative [N] waves when detected by electroencephalography or
EEG), that is generated within the visual system following the presentation of a
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stimulus. Reduced amplitude in positive P100 waves (Doniger, Foxe, Murray,
Higgins & Javitt, 2002; Schechter et al., 2005; Thompson & Drasdo, 1992; Vohs et al., 2008; Yeap et al, 2008), P300 and C100 waves, negative N100 amplitudes
(Doniger et al., 2002; Schechter et al., 2005; Vohs et al., 2008) and prolonged P300b latency (Vohs, et al., 2008) have been observed in individuals with schizophrenia and their siblings (Groom et al., 2008). Although a feature of schizophrenia, abnormal
P300 amplitudes are thought to be more characteristic of functional psychosis in general, rather than being specific to schizophrenia (Bestelmeyer, Phillips, Crombie,
Benson & St Clair, 2009).
Visual-evoked potentials can also be measured in response to particular stimuli to further investigate specific visual abnormalities. For example, altered VEP spatial frequency functions have been observed in schizophrenia (Clementz, Wang & Keil,
2008; Celesia & Toleikis, 1991). Abnormal VEPs in tasks using stimuli that preferentially stimulate magnocellular or parvocellular pathways have been observed in schizophrenia (Butler et al., 2001; Butler et al., 2005; Butler et al., 2007; Kim,
Wylie, Pasternak, Butler & Javitt, 2006). These findings confirm the existence of early-stage visual processing dysfunction in schizophrenia (Butler et al., 2005).
Abnormal steady-state VEPs (evoked potentials measured during continuous stimulation) have been observed in schizophrenia during visual processing of complex visual tasks. P300b amplitudes have been observed to be lower in the parietal regions in identity and happiness tasks (in those with schizophrenia compared to controls using an oddball paradigm to evaluate face identity recognition and facial emotional recognition of happiness and fear) (Ramos-Loyo, Gonzalez-
Garrido, Sanchez-Loyo, Medina & Basar-Eroglu, 2009). This implicates higher- order processing. It has been proposed that abnormal N250 suggests that those with
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schizophrenia are less efficient at decoding features of facial affect (Wynn, Lee,
Horan & Green, 2008). Individuals with schizophrenia showed abnormal P100 and
N170 responses to spatial frequency changes in faces, thus demonstrating decreased ability to process facial features (Obayshi et al., 2009). P100 amplitude reductions that occur early in visual processing have been implicated in working memory deficits and have been observed in adolescents with schizophrenia and are a feature of early onset psychosis (Haenschel et al., 2007). These disruptions of visual steady- state responses in schizophrenia are consistent with neuropathological and medical resonance imaging (MRI) evidence of anatomic abnormalities in visual cortices
(Brenner et al., 2009). Visual-evoked potentials (and contrast sensitivity measures) significantly predict community functioning in schizophrenia (Butler et al., 2005), suggesting that abnormal visual processing contributes to the fundamental cognitive decline and perceptual disturbances seen in the disorder.
In schizophrenia, event-related brain potentials have revealed reduced inter- hemispheric co-operation and slower corpus-callosal transfer times when information is presented to the right hemisphere. Visual information appears to require more time to cross from the right to the left hemisphere for analysis, thereby reducing the speed of visual information processing in these individuals (Endrass, Mohr & Rockstroh,
2002; Mohr, Pulvermuller, Rockstroh & Endrass, 2008; Schwartz, Winstead &
Walker, 1984). Significant correlation between left- and right-hand bisection errors and loss of callosal integrity (McCourt, Shpaner, Javitt & Foxe, 2008) is suggestive of abnormal connectivity between frontal and parietal circuits (Frecska, White &
Luna, 2004) in schizophrenia. Slow transfer speed and lack of connectivity may contribute to thought disorder, poverty of thought and prominent perceptual hallucinations (McCourt et al., 2008). This abnormal connectivity between cortical
Literature Review - Visual Processing in Schizophrenia and Binocular Rivalry 9
regions renders individuals with schizophrenia less able to predict the relation between ‘action’ and ‘effect’. This difficulty strongly correlates with severity of positive psychotic symptoms, specifically delusions and hallucinations (Voss et al.,
2010).
Andreasen, Paradiso and O'Leary (1998) postulated that a cortico-cerebellar- thalamic-cortical brain circuit is responsible for fluid, temporal coordination of sequences of behaviour. The cognitive fragmentation, or thought disorder, in schizophrenia is likely to be due to timing anomalies associated with cortico- cerebellar-thalamic-cortical brain circuit dysfunction (Bolbecker, Mehta, Edwards,
Steinmetz, O'Donnell & Hetrick, 2009). This has been termed ‘cognitive dysmetria’; meaning difficulty in prioritising, processing, coordinating, and responding to information. This ‘poor mental coordination’ is a fundamental cognitive deficit in schizophrenia, and can account for its broad diversity of symptoms (Andreasen et al.,
1998). A meta-analysis of published functional neuroimaging studies showed that individuals with schizophrenia have lower activation of most right-hemisphere regions of the cortico-cerebellar-thalamic circuit; a pattern that further indicates poor connectivity between brain regions (Ortuno, Guillen-Grima, Lopez-Garcia, Gomez &
Pla, 2010). This timing circuit may be connected with cognitive tasks also known to be abnormal in schizophrenia (Andreasen & Pierson, 2008).
1.4.2 Functional magnetic resonance imaging Studies (fMRI) in schizophrenia.
Functional magnetic resonance imaging studies (fMRI) reveal that individuals with schizophrenia, and their biological relatives, generate a greater number of leading saccades during smooth-pursuit eye movement (Schwartz, O’Brien, Evans,
Sautter & Winstead, 1995; Schwartz et al., 1995). Slowed initial pursuit velocity, more errors in pursuit tasks (Radant, Claypoole, Wingerson, Cowley & Roy-Byrne,
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1997; Radant & Hommer, 1992), and abnormal saccadic eye movements (Mather,
1986; Mather & Putchat, 1984; Schreiber et al., 1995) may reflect a trait for the disorder (Bender, Weisbrod & Resch, 2007; Holzman, 1987; Keri & Janka, 2004;
Kinney, Levy, Yurgelun-Todd, Kajonchere & Holzman 1999; Levy, Holzman,
Matthysse & Mendell, 1994; Levy, Holzman, Matthysse & Mendell, 1993; Thaker,
2008). This is supported by twin studies (Holzman et al., 1988; Holzman, Levy,
Matthysse & Abel, 1977; Litman et al., 1997) where children with childhood-onset schizophrenia exhibit a pattern of eye-tracking abnormalities similar to that seen in adults with schizophrenia (Kimra et al., 2001). These abnormalities have been associated with the compromised ability of individuals with schizophrenia to process new and complex information (Schwartz et al, 1995).
Abnormalities in motion detection have been demonstrated using fMRI (Chen,
Levy et al., 1999; Chen, Palafox et al., 1999; Chen, Levy, Sheremata & Holzman,
2004; Chen et al., 2008; Low, Rockstroh, Elbert, Silberman & Bentin, 2006). Global
(direction of random dot patterns) rather than local (detection of moving gratings) stages of the visual-motion processing system are impaired in those with schizophrenia. Motion-sensitive brain areas, such as the middle temporal area and medial superior temporal areas, where processing of large receptive fields for spatial and temporal integration occurs (Chen, Makayama et al., 2003) are implicated in schizophrenia. Signal changes detected by blood oxygen level dependence (BOLD) fMRI in motion-detection tasks, consistent with cortical activation, were significantly reduced in the middle temporal area (MT) and significantly increased in the inferior prefrontal cortex (an area normally involved in higher-level cognitive processing).
This shift in cortical response from posterior to prefrontal regions suggests that
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motion perception in schizophrenia is associated with both deficient sensory processing and compensatory cognitive processing (Chen et al., 2008).
Individuals with schizophrenia demonstrate temporal resolution deficits when processing sequential information, such as moving dots, gratings or letters (Schwartz,
Maron, Evans & Winstead, 1999a) and tasks involving visuospatial working memory
(Bollini, Arnold & Keefe, 2000; Silver & Goodman, 2008). When the attentional load of a visual monitoring task in schizophrenia was measured during fMRI selective visual processing was integrated in posterior parietal areas, rather than the earlier occipital cortex (Schwartz et al., 2004). These factors may be manifested as the misinterpretation of visual (and other) perceptual stimuli commonly observed in psychosis. Relative to control subjects, fMRI reveals that patients with schizophrenia show markedly-reduced activation to low, but not high spatial frequencies in multiple regions of the occipital, parietal, and temporal lobes
(Martinez et al., 2008). Low spatial frequency processing is suggestive of disrupted magnocellular processing, necessary in locating and identifying moving visual stimuli, that contributes to the perceptual and cognitive disturbances associated with schizophrenia (Chen et al., 2008; Laycock, Crewther & Crewther, 2008).
1.4.3 Magnocellular and parvocellular visual pathways in schizophrenia.
Abnormalities associated with magnocellular (or ‘transient’) visual pathways have been consistently reported in schizophrenia (Butler et al., 2001; Cadenhead,
Serper & Braff, 1998; Green, Nuechterlein & Mintz, 1994b; Green, Nuechterlein,
Mintz, 1994a; Kim et al., 2006; Schwartz & Winstead, 1998; Schwartz et al., 1994;
Slaghuis & Curran, 1999). Some have suggested that magnocellular pathway deficits are an endophenotype for schizophrenia (Bedwell & Orem, 2008; Butler, Harkavy-
Friedman, Amador & Gorman, 1996; Green, Nuechterlein & Breitmeyer, 1997;
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Buttner et al., 1999; Hayashi, 2000; Holzman, 1987; Keri, Bendek & Janka, 2001;
Keri, Szendi, Kelemen, Benedek & Janka, 2000; Keri, Kelemen, Benedek & Janka,
2004; McClure, 2001).
The magnocellular (or ‘transient’) visual pathway integrates dynamic visual information regarding the position and spatial relationships of visual stimuli. In broad terms, this is the attention-capturing pathway (Schwartz et al., 1988). In schizophrenia, the transient (or magnocellular) pathways are thought to be either impaired or over-active, interrupting the neural processing of the sustained (or parvocellular) visual pathway (Butler et al., 2003). Over-active magnocellular pathways correlate with poor selective attention, poor concentration, heightened awareness of background noise and distractibility (Butler et al., 2003). Individuals with schizophrenia have difficulty filtering sensory information related to importance
(Hetrick, Erickson & Smith, 2010). These features are the most-frequently associated symptoms of the disorder.
To investigate these abnormalities, experimental techniques have been developed to assess early visual magnocellular or parvocellular pathway processing that contributes to higher-order cognitive impairments. Many researchers have observed deficits in magnocellular pathway processing in subjects with schizophrenia using frequency-doubling tasks, (Keri et al., 2004) steady-state VEPs
(Kim et al., 2006) and backward masking tasks (Green & Nuechterlein, 1999; Green
Nuechterlein, Breitmeyer & Mintz, 1999; McClure, 2001; Nuechterlein, Dawson &
Green, 1994; Rund & Landra, 1990; Skottun & Skoyles, 2009). However, not all researchers report magnocellular abnormalities in schizophrenia (Skottun & Skoyles,
2007). Delord et al., (2006) found no magnocellular dysfunction in participants with schizophrenia using a four-alternative forced-choice luminance discrimination task; a
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task hypothesised to access visual processes early in the visual pathways. They concluded that if magnocellular dysfunction is a feature of schizophrenia, the abnormality is likely to reflect integrative processes at higher cortical levels where the magnocellular and parvocellular paths interact.
1.4.4 The cerebral hemispheres and schizophrenia.
Schizophrenia is generally thought to involve disturbance of right hemisphere mechanisms involved in spatial perception and sustained attention (Evans &
Schwartz, 1997; O’Donnell et al., 2002). In right-handed individuals with schizophrenia, the left hemisphere is superior for temporal sequential analysis
(Schwartz et al., 1984). Subtle right-hemisphere dysfunction has been noted in individuals diagnosed with schizophrenia, and in individuals at high risk for schizophrenia (Leib et al., 1996). Others have observed laterality differences that suggest the left hemisphere may be less efficient than the right (Holzman, 1987).
Spatial working memory deficits are more severe in the left hemisphere in patients with schizophrenia and in 'psychosis-prone' individuals (Park, 1999). Poorer reaction times in response to visuospatial information in schizophrenia also implicate left hemispheric mechanisms (Frecska, White et al., 2004; Gastaldo, Umilta, Bianchin &
Prior, 2002) and frontal function (Levander, Bartfai & Schalling, 1985).
1.4.5 Neurotransmitters in schizophrenia.
In addition to brain region and pathway dysfunction, abnormalities at the cellular level have been implicated in schizophrenia. Alterations in the structure of neurons results in a loss of synaptic connectivity and the ability to transmit afferent information (Benitez-King, Ramirez-Rodriguez, Ortiz & Meza, 2004). Abnormal neurotransmission is a hallmark of schizophrenia, with a number of neurotransmitters and neurotransmission pathways involved (Javitt, 2009). These include dopamine,
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glutamate, gamma aminobutyric acid (GABA), serotonin and acetylcholine (Benitez-
King, Ramirez-Rodriguez, Ortiz & Meza, 2004). However, the dopamine theory of schizophrenia has remained the most dominant in the schizophrenia research literature. The dopamine theory is based on observations that substances that increase dopamine levels in the brain (for example, amphetamines) induce schizophrenia-like symptoms (or psychosis) (Kapur & Mamo, 2003). However substances that block dopamine (for example, antipsychotic medications, such as
Chlorpromazine) or antagonise dopamine receptors (particularly D2 receptors) improve or reverse these symptoms (Kapur & Mamo, 2003).
Dopaminergic pathways predominantly project to the pre-frontal cortex in humans, which prompted ‘top-down’ models to explain dysfunction in schizophrenia
(Javitt, 2009). Studies utilising the visuospatial working memory (George et al.,
2002), memory-related visual and cognitive tasks (McGowan, Lawrence, Sales,
Quested & Grasby, 2004; Sheremata & Chen, 2004) and neuroimaging studies
(McGowan et al., 2004; Tost, Alam & Meyer-Lindenberg, 2009) suggest top-down visual-processing disturbances. However, studies in individuals with schizophrenia that utilise spatial, temporal, and contrast sensitivities known to be mediated by dopamine and dopamine receptors, suggest that dopamine-related dysfunction originating in the primary visual pathway contribute to abnormalities detected at higher levels of visual processing in schizophrenia (Chen et al., 2003; Harris, Calvert
& Snelgar, 1990; Keri, Antal et al., 2002; Keri, Janka & Benedek, 2002; Masson,
Mestre & Blin, 1993; Schwartz et al., 1988; Schwartz, 1990; Sheremata & Chen,
2004; Slaghuis, 1998; Slaghuis & Curran, 1999).
Both serotoninergic and dopaminergic systems are important in visuospatial attention tasks that involve attentional performance, selective attention, vigilance and
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executive control exerted by the prefrontal cortex and striatum (Boulougouris &
Tsaltas, 2008; Chudasama & Robbins, 2004) and abnormal saccades (Gurvich,
Fitzgerald, Feorgiou-Karistianis & White, 2008). Visuospatial working memory is partially mediated by prefrontal cortical dopamine, and dysregulation of prefrontal cortical dopamine systems may contribute to the pathophysiology of schizophrenia
(George, Vessicchio, Termine, Sahady, Head, Pepper, Kosten & Wexler, 2002), suggesting ‘top-down’ processing. Ketamine, a-N-methyl-d-aspartate (NMDA) antagonist, disrupts leading saccades during smooth-pursuit eye movements in schizophrenia (Avila et al., 2002). Dopamine imbalances (striatal excess and cortical deficiency) in schizophrenia may be secondary to NMDA hypofunction in the prefrontal cortex and its connections (Kapur & Seeman, 2002; Laruelle, Kegeles &
Abi-Dargham, 2003).
1.4.6 Dopamine genes in schizophrenia.
In recent times, researchers have investigated the genetic determinants of schizophrenia and how genetic factors may moderate symptoms and treatment outcomes. Many dopaminergic genes have been investigated in schizophrenia including: DRD1, DRD2, DRD3, DRD4 and DRD5 receptor genes, catechol-O- methyltransferase (COMT) and dopamine-transporter genes (DAT). Although multiple polymorphisms of each of gene have been investigated in schizophrenia, most are restricted to single studies or provide inconsistent results across studies
(Talkowski, Bamne, Mansour, Vishwajit & Nimgaonkar, 2007). The most researched dopamine polymorphism in the literature is the Taq1 A allele of the
DRD2 receptor gene. There have been a number of associations and functional interactions in schizophrenia investigated with this polymorphism, thereby making the Taq1 A allele of the DRD2 receptor gene the most promising to investigate in the
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current study. Investigations into the effect of anti-psychotic medications in schizophrenia in the presence of the A1 allele indicate that this polymorphism may modify the efficiency of DRD2 antagonism of such drugs in the central nervous system (Suzuki, Mihara et al., 2002). Serum prolactin levels, that index dopamine
D2 blockade (Cotes, Crow & Johnstone, 1997; Gruen, 1978, Seeman, 2002), are in those with schizophrenia who are A1+ (that is, positive for the A1 allele of the
DRD2 receptor gene) receiving anti-psychotic medications compared to those without (Young et al., 2004). It has been noted that individuals with schizophrenia who are A1+ (A1/1A1 and A1/1A2 genotypes) tend to experience more favourable responses to medications (Scharfetter, 2004) than those with A1- status (A2/A2 genotype). A1+ individuals show greater improvement in total Brief Psychiatric
Rating Scale (BPRS) scores and in positive symptoms with treatment (Suzuki,
Mihara et al., 2000), again indicating that the allele may have a moderating effect.
1.4.7 Perceptual rivalry in schizophrenia.
Bistable or ambiguous figures such as the Necker Cube, Rubin’s Vase, duck/rabbit and Schroder’s Staircase (Meng & Tong, 2004; Miller, Gynther, Heslop,
Liu, Mitchell, Ngo, Pettigrew & Geffen, 2003), present pictorial images to the visual system that can be perceptually organised in several ways (Meng & Tong, 2004).
These figures require the visual system to interpret information from two equally- compelling interpretations. This results in spontaneous perceptual alternations between the two images; a phenomenon known as perceptual rivalry. It is thought that perception rivalry results from lateral competition between neural mechanisms or alternative images at some level in the visual pathway (Tong, 2001; Meng &
Tong, 2004). However, there is debate as to exactly where this competition occurs.
Using event-related potentials, it has been demonstrated that perceptual rivalry is
Literature Review - Visual Processing in Schizophrenia and Binocular Rivalry 17
resolved before perceptual awareness is established at 200-300 msec (Kornmeier &
Bach, 2004), suggesting competition at lower levels in the visual system. However, other studies indicate that competition occurs in higher cortical regions of the visual system. Single-cell studies have suggested that fronto-parietal areas initiate the competition during perceptual rivalry by sending top-down signals to guide activity in the visual cortex toward one representation at a time (Leopold & Logothetis,
1999). These studies are supported by fMRI data that show that activity in frontal and parietal areas correlate with perceptual alternations reported when viewing bistable images (Lumer, Friston & Rees, 1998).
Difficulty integrating incoming visual information and attentional selection has been associated with the perceptual disturbances and delusions observed in schizophrenia (Stephan, Friston & Frith, 2009; Synofzik, Thier, Leube, Schlotterbeck
& Lindner, 2010). Individuals with schizophrenia have demonstrated abnormal visual processing associated with early cortical processing (for example, deficits that occur between 100-300 msec, discussed above in Section 1.3.1) and in deficits in higher cortical regions (as discussed in Sections 1.3.2). Therefore, it is likely that those with schizophrenia would also show impaired performance on perceptual rivalry tasks.
Available perceptual rivalry data in schizophrenia inconclusive. Levander et al., (1985) suggest slower reversals in subjects with schizophrenia. An earlier study
Hunt and Guilford (1933) demonstrated Necker cube reversals were not significantly different to healthy controls in subjects with ‘dementia praecox’ (an older term for schizophrenia), but were four times faster than those with manic depression. Using the ‘Schroder’s Staircases’, Calvert et al., (1988) demonstrated that subjects with schizophrenia perceived the staircase from above for significantly less time, and had
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a (non-significant) tendency to have more reversals than controls. More recent studies, such as Hoffman, Quinlan, Mazure and McGlashan (2001) and Keil, Elbert,
Rockstroh and Ray (1998) have demonstrated that subjects with schizophrenia had faster reversals compared to healthy controls using Rubin’s Vase and the Necker
Cube. It has also been demonstrated that long term anti-psychotic therapy has no significant effect on reversal rate or dominance duration during perceptual rivalry
(Calvert et al., 1988).
1.4.8 Binocular rivalry in schizophrenia.
Binocular rivalry is a unique type of perceptual rivalry where two opposing images (that cannot be fused into a single stable image) are presented to each eye exclusively. Each eye’s image during binocular rivalry is perceived in alternating fashion. Binocular rivalry is thus considered to be competition between the eyes, rather than between images or patterns (Tong, 2001). Similar to perceptual rivalry, the mechanisms involved in binocular rivalry are widely debated. Some suggest competition in the primary visual pathway (Blake,1989; Tong, 2001; Meng & Tong,
2004), while others suggest that mechanisms higher in cortical regions (Lumer,
Friston & Rees, 1998; Leopold & Logothetis, 1999) or cortical hemispheres
(Pettigrew & Miller, 1998; Miller, Liu, Ngo, Hooper, Riek, Carson & Pettigrew,
2000; Miller, 2001) are responsible for the competition between images presented to each eye.
Binocular rivalry has the advantage as a research method that each of the rival stimuli can be altered to access specific aspects of the visual system. For example, the stimulus presented to one eye may be a complex image (such as a face), and the other may be a simple grid pattern (see Blake, 2001), to determine how visual information is integrated and processed. The stimuli may also be presented at
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differing temporal or spatial frequencies or luminance to examine the effect of processing early in the visual pathway (Blake, 2001; Liu, Tyler & Schor, 1992). The specific effect of altering the stimuli can be measured by alternations over time
(binocular rivalry rate) or how long each image dominates (dominance duration).
Each image dominates for a fluctuating period of time, indicative of non-linear dynamic processing within the visual system. Non-linear processes are also associated with other biological phenomena, such as the cortical spreading that occurs in depression and slow-wave sleep (Tong, 2001). These characterisitics of binocular rivalry provide an opportunity to investigate the neural components of conscious visual awareness (Blake & Logethetis, 2002) in clinical populations, including in those with schizophrenia. By exploiting the visual deficits known to be a feature of schizophrenia, and investigating factors that contribute to visual awareness and selective visual attention, binocular rivalry may provide novel insights into cortical processing in schizophrenia in specific cortical regions and pathways within the visual system.
To date, there are few studies of classical binocular rivalry in schizophrenia.
(Miller et al., 2003) reported no significant differences binocular rivalry rates in subjects with schizophrenia compared to those with depression or healthy controls; however (Foxe, 1965; Frecska et al., 2003; Sappenfield & Ropke, 1961; Wright, et al., 2003) report slower binocular rivalry rates in schizophrenia. Pettigrew and
Miller and colleagues have proposed that slow binocular rivalry rate is a trait maker for bipolar disorder (see Pettigrew & Miller, 1998 and Miller et al., 2003), and not schizophrenia. They suggest that slow binocular rivalry rate may be a helpful tool in diagnosis. However, this issue remains unresolved, as there are conflicting reports.
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There are limited data related to eye swapping during binocular rivalry tasks in subjects with schizophrenia. As discussed previously, eye swapping eliminates eye- of-origin information, so explores ‘top–down’ visual processing. Frecska, White et al., (2003), White et al., (2001) and Wright et al., (2003) have applied conflicting stimuli to the eyes in rapid reversal in subjects with schizophrenia in a method they coined ‘dichoptic stimulus alternation’. Binocular rivalry ceased in healthy control subjects when dichoptic stimulus alternations were above 30 Hz, however approximately half of subjects with schizophrenia continued to experience rivalry under these conditions (White et al., 2001). Healthy controls reported a consistent image (vertical or horizontal stripes) for up to one second, while those with schizophrenia perceived stable images for up to four seconds (Sec) during dichoptic stimulus alternation (even when the stimuli were swapped at 30 Hz) (Frecska, White
& Leonard et al., 2003; Wright et al., 2003). Increased dominance durations, and thus binocular rivalry rate, observed in schizophrenia under dichoptic stimulus alternation may be related to less-effective visual processing. These may result from slow gamma oscillations within the visual pathway (Frecska, White et al., 2003). These factors may account for the perceptual disturbances and visual processing anomalies associated with the hallucinations, delusions and cognitive deficits observed in schizophrenia.
Studying binocular rivalry in schizophrenia provides a unique opportunity to investigate components of visual sensory input that ultimately affect perceptual awareness. A systematic investigation in binocular rivalry in schizophrenia is missing from the current literature. Advancing the understanding of the mechanisms involved in binocular rivalry and brain functioning with regard to visual awareness
Literature Review - Visual Processing in Schizophrenia and Binocular Rivalry 21
may provide insights into cortical processing in schizophrenia. The focus of this review now turns to binocular rivalry.
1.5 Binocular Rivalry
As noted, binocular rivalry refers to the perceptual alternation of images that occurs when two dis-similar images are presented simultaneously, one to each eye, in the same spatial location (Blake, 2001; Logethietis, Leopold & Sheinberg, 1996;
Tong & Engel, 2001). For example, when vertical lines are presented to one eye and horizontal lines are presented to the other in the same retinal location, the vertical and horizontal lines are perceived in alternating fashion, rather than forming a grid or composite pattern. During binocular rivalry the observer perceives the opposing images in alternating fashion, even though the sensory input to each eye remains constant. The alternation of perceptual images is therefore dissociated from the sensory input (Clifford, 2009), allowing a unique opportunity to investigate human visual perceptual awareness, or the ‘neural correlates of consciousness’ (Crick &
Koch, 1998). Thus, in recent times the focus of binocular rivalry research has been the investigation of factors affecting the dominance of one image for awareness, and subsequent suppression of the other. Reciprocal suppression and awareness during rivalry are linked to conscious perception (Mitchell, Stoner & Reynolds, 2004; Ooi
& He, 1999; Tong, Nakayama, Vaughan & Kanwisher, 1998). It is this feature that makes binocular rivalry a useful tool to investigate the contribution of perceptual and cortical processes to the cognitive deficits observed in neurocognitive disorders, such as psychosis and mood disorders.
Binocular rivalry testing yields two measures. The first is the frequency of perceptual alternation between images (binocular rivalry rate), generally expressed as alternations per second (Hz). The second is the portion of time spent perceiving the
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image of one eye relative to the other, assessed by predominance or perceptual dominance durations (Blake, 2005; Breese, 1899; Levelt, 1968) in seconds.
Inhibitory processes during rivalry behave in an ‘all or none’ fashion (Blake &
Camisa, 1979), typically causing the suppressed image to return to dominance within
20 msec (Walker & Powell, 1979).
It is argued that the factors that affect the rate, rather than dominance or suppression durations are the most critical to understanding the underlying process of binocular rivalry (Chen & He, 2003). Binocular rivalry rates are thought to be driven by monocular image contrast during the suppressed phase (Mueller & Blake, 1989), with rates decreasing monotonically with increasing stimulus strength (Levelt, 1968;
Shpiro, Curtu, Rinzel & Rubin, 2006). It is generally accepted that manipulations to the rival stimuli can modulate binocular rivalry rate (increasing or decreasing dominance durations), however the fluctuations in perception between the two images are ‘hard wired’ into the visual system (Blake, 2005). Breese (1899) made the observation that subjects could exert some control over the length of time they could perceive the dominant image during binocular rivalry; however they could not control the fluctuations between images. Therefore, binocular rivalry rate may provide some measure of underlying cognitive efficiency (Fox, 1965).
The alternation of perceptual images during rivalry has been argued to reflect cortical responses to active, programmed events initiated by brain areas that integrate sensory and non-sensory information to coordinate behaviour (Leopold &
Logothetis, 1999). When dominance durations are expressed as a function of their mean and plotted as histograms, they typically approximate gamma-density functions
(Carter & Pettigrew, 2003; Fox & Herman, 1967; Levelt, 1968; Miller, 2001; Miller et al., 2003; O’Shea, Parker, La Rooy & Alais, 2009) although this less convincing in
Literature Review - Visual Processing in Schizophrenia and Binocular Rivalry 23
some studies, (Kobayashi, 1992). Leopold (1999) suggests activity throughout the visual cortex in higher, largely non-sensory brain centres, is consistent with perceptual reversals during rivalry. This activity is associated with planning and motor programming, and serves an important role in perceptual organisation and selective attention. However, Levelt (1968) argued that mechanisms lower in the visual system are responsible for the alternations in rivalry. He argued that suppressed images produce, “A series of randomly-distributed excitation spikes”, that were related to a ‘flick’ in eye-movements, and that these were necessary for the suppressed image to return to dominance. He noted that plotted time intervals of each of these ‘flicks’ fitted gamma distributions. The parameters of these distributions were consistent between subjects (Logothetis et al., 1996).
Although several authors have fitted dominance durations to gamma distributions, others note that binocular rivalry dominance durations can also be fitted to Weibul, log-normal (Lehky, 1995; Zhou, Gao, White, Merk & Yao, 2004),
Wiener and Capocelli-Riciardi distributions (De Marco, Penego & Trabucco, 1977).
Voluntary control changes the shape of the distributions (Van Ee, Noest, Brascamp
& van den Berg, 2006). These observations question whether gamma distributions are truly a mechanism of binocular rivalry, and therefore perception. Thus, the validity of gamma-distribution-based computer models to describe the neural events during binocular rivalry have been questioned (Brascamp, van Ee, Pestman & van den Berg, 2005; Brascamp et al., 2006; Kobayashi, 1992; Murata, Matsui, Miyauchi,
Kakita & Yanagida, 2003; Sugie, 1982).
1.5.1 Stimulus parameters moderate binocular rivalry
Investigations into the binocular rivalry phenomenon have spanned a century with most attention on the effect of stimulus features on binocular rivalry. ‘Strong’
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figures (in terms of figure-ground contrast) are thought to alternate more quickly than ‘weak’ (figure-ground contrast) when viewed stereoscopically (Alexander,
1951) and rivalry rate is faster the more disparate the competing stimuli (Whittle,
1965). Additionally, changing the temporal frequency, spatial frequency or contrast of an image at the beginning of suppression alters the course of binocular rivalry
(Walker & Powell, 1979).
The perception of binocular rivalry stimuli depends on temporal and spatial frequency, contrast and luminance of the rival stimuli (Lui, Tyler & Schor,1992), along with the size (Blake, O’Shea & Muller, 1992; O’Shea et al., 2009) colour
(Andrews & Purves, 1997; Hong & Shebell, 2008a; O’Shea & Williams 1996; Ooi &
Loop, 1994; Wade, 1975), orientation (O’Shea, 1997; Andrews & Purves, 1997;
Blake & Lema, 1978) and context of each image (Blake, 2001; Carter, Campbell, Lui
& Wallis, 2004; Hong & Shevell, 2008b).
1.5.1.1 Spatial frequency.
The spatial frequencies that produce the crispest binocular rivalry are those between 2 cycles per degree (cpd) (Carlson & He, 2000) and 10 cpd (Livingstone &
Hubel, 1987). When the spatial frequency of the stimuli presented to each eye is equal, gratings of high spatial frequency (and especially those of low contrast) tend to fuse to produce a stable perception of a dichoptic plaid (Burke, Alais &
Wenderoth, 1999). Lower spatial frequency gratings typically alternate. The greater the difference between the spatial frequencies of the stimulus presented to each eye, the faster the binocular rivalry rate (O’Shea, 1997; Wade 1994). O’Shea (1997) noted that when exclusive visibility of one grating relative to the other was plotted, an inverted U-shaped relationship with spatial frequency emerged. The peak of this curve shifted to larger spatial frequencies as the field size increased (O’Shea, Sims &
Literature Review - Visual Processing in Schizophrenia and Binocular Rivalry 25
Govam, 1997). These findings suggest that spatial frequency channels in human vision are employed during binocular rivalry (Fahle, 1982), where each spatial- frequency-dependent cortical column inhibits only the adjacent column (Aladi,
1976). Each cortical column is a basic unit for sensory processing, containing neurons with similar spatial-response properties stacked on top of each other in different layers throughout the depth of the cortex.
1.5.1.2 Movement.
Flickering images, eye blink and moving stimuli all produce transient stimulation across the retina (Blake & Fox, 1974). A moving image (irrespective of speed and direction) presented to one eye remains visible for longer than a static image presented to the other (Blake, Yu, Lokey & Norman 1998; Wade, 1994).
Moving rivalrous stimuli presented at equal strength to each eye, lead to a greater suppression than static patterns (Norman, Norman & Bilotta, 2000; Cobo-Lewis,
Gilfory & Smallwood, 2000).
1.5.1.3 Luminance.
Dominance or suppression of rival images is determined by the relative image luminance contrast between the two eyes, with dominance of the higher-contrast image being favoured (Freeman & Nguyen, 2001; Mueller & Blake, 1989; Whittle,
1965). Blurred patterns are suppressed by sharply-focused ones (Fahle, 1982), and textured stimuli of high contrast (randomly-orientated patches) are more dominant than uniform textures (Bonneh & Sagi, 1999). Functional magnetic resonance imaging studies (fMRI) indicate that when luminance contrast is increased in one eye, activity in the primary visual cortex (V1) increases, and decreases with a lower contrast image (Polonsky, Blake, Braun & Heeger, 2000). At very low luminance,
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rivalry does not occur, allowing a stable summation between the two images to form
(Lui et al., 1992).
1.5.1.4 Colour.
Presenting images of different colours to each eye increases rivalry (Andrews
& Purves, 1997; Hong & Shevell, 2008a; Oois & Loop, 1994; O’Shea & Williams,
1996; Wade, 1975). Long-, medium- (Rogers et al., 1977) and short-cone pathways all contribute to binocular rivalry (O’Shea & Williams, 1996). However, it has been shown that opposing gratings that differ with respect to chromaticity can produce a unified percept of mixed colour at high-luminance contrast (Hong & Shevell, 2006).
Counter phased gratings of different colours, equal in terms of their luminance and chrominance, produce a single, fused moving grating (Carney, Shadlen & Switkes,
1987).
1.5.1.5 Orientation.
Greater differences in orientation between the two eyes increases binocular rivalry rate (Andrews & Purves, 1997; O’Shea, 1997). Threshold levels for the mechanism responsible for suppression operating non-selectively over a wide range of orientations (Blake & Lema, 1978). It is argued that binocular rivalry occurs early in the visual pathway as orientation-selective channels are monocularly driven.
Orientation response is hypothesised to be established before the level at which the two monocular channels converge (Walker, 1978). Changes during rivalry between stimuli differing in orientation occur after about 100 msec (P1) (Veser, O’Shea,
Schroger, Trujillo-Barreto & Roeber, 2008). There is some agreement that vertical gratings predominate over horizontal gratings (vertical gratings are viewed for approximately 30% longer) (Wade, 1994).
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1.5.1.6 Size.
Binocular rivalry is affected by the size of the rival images (O’Shea et al.,
2009). Presenting different-sized stimuli to each eye increases binocular rivalry rate
(Andrews & Purves, 1997), and for a given-sized target exclusive visibility increases with retinal eccentricity (Blake et al., 1992). The optimal size for targets to gain exclusive visibility during rivalry is a diameter of 5.3 or 7.3 minutes of visual angle
(Blake et al., 1992), with the target size being inversely proportional to spatial frequency (O’Shea et al., 1997).
1.5.1.7 Context.
Contradictory contextual information increases dominance duration during binocular rivalry (Blake, 2001; Carter, Campbell et al., 2004; Hong & Shevell,
2008b). When different objects are presented to each eye at the same location in visual space, they are likely to rival even if all of the other stimulus features (such as colour) are identical. Conversely when different, monocular stimuli (with respect to colour and luminance) represent the same object at the same location in space, fusion is more likely to result (Andrews & Lotto, 2004).
1.6 Theories of Binocular Rivalry
Two opposing theories have dominated the binocular rivalry phenomenon.
One suggests that binocular rivalry involves inter-ocular competition or “eye rivalry”
(a “bottom-up” theory). While the other suggests binocular rivalry is competition of the perceptual images higher in the visual cortex or “pattern rivalry” (a “top-down” theory) - see Blake (1989) and Tong (2001) for reviews. Bottom-up theorists of binocular rivalry argue the alternation of images during binocular rivalry is due to events in the early stages of visual perception; that is, in the primary visual pathway
(Tong & Engel, 2001). Detailed investigation of the effect of specific features of the
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rival stimuli and manipulation of stimulus features has on the binocular rivalry phenomena have provided insights into visual information processing at higher levels of the visual pathway. These insights have informed our understanding of cognition, memory and executive functioning.
Conversely ‘top-down’ theorists posit that during binocular rivalry the observer attends to, or selectively concentrates on, one image while ignoring the other. Thus, higher-level cortical processes influence what the observer perceives. Researchers investigating binocular rivalry using a ‘top-down’ approach examined the effect that higher-order cognitive processing (i.e. visual memory, planning and decision making) has on visual perception (Li, Freeman & Alais, 2005; Logothetis, 1998;
Logothetis et al., 1996).
Theorists have also suggested binocular rivalry involves hierarchical processing that involve both ‘top-down‘ and ‘bottom-up’ neural processes (Blake &
Logothetis, 2002; Pearson & Clifford, 2005). Others suggest competition between visual pathways (Carlson & He, 2000; Livingstone & Hubel, 1987; Nguyen,
Freeman & Alais, 2003) or the cortical hemispheres (Carter & Pettigrew, 2003;
Carter et al., 2005; Miller et al., 2000; Miller et al., 2003; Pettigrew & Miller, 1998;
Ngo, Lui, Tilley, Pettigrew & Miller, 2008). Evidence for and against these four theories (i.e. bottom-up, top-down, pathway and inter-hemispheric processing) will be critically reviewed.
1.6.1 Bottom-up theories of binocular rivalry.
Evidence drawn from psychophysical studies suggests that binocular rivalry is fully resolved at the earliest stages of cortical processing in monocular V1 neurons
(Tong & Engel, 2001). Thus, binocular rivalry is hypothesised to be the result of inter-ocular competition, with suppression and dominance between the two eyes
Literature Review - Visual Processing in Schizophrenia and Binocular Rivalry 29
occurring early in the visual system, where the two neural inputs from the eyes converge (Levelt, 1965). Central to this model are three basic concepts. Firstly, signals from each monocular stimulus travel down pathways that connect to monocular cortical areas to higher areas that subserve perception. Secondly, that at any one moment during binocular rivalry one of these pathways is suppressed
(neurons along the pathway are suppressed) and, finally, that the depth of suppression (or the suppression threshold) increases along the suppressed pathway
(Freeman, Nguyen & Alais, 2005).
Tong (2001) presented opposing rival stimuli to each eye and measured the activity of the area in the primary visual cortex representing the blind-spot using fMRI. Tong found larger activation in the blind-spot area when gratings presented to the ipsilateral eye were dominant, as opposed to when they were suppressed. This suggests that binocular rivalry is resolved within the monocular visual cortex. These findings indicate V1 may be important for processing conscious visual information.
This is supported by Polonsky et al., (2000) who found that rivalry-related fluctuations in V1 activity are roughly equal to those observed in other visual areas
(i.e. V2, V3, V3a and V4), indicating that neural mechanisms responsible for binocular rivalry are localised early in the visual pathway. Therefore, it is possible that V1 plays a role as a ‘gatekeeper’ of consciousness (Tong & Engel, 2001), and that neurons in the primary visual cortex have a direct role in visual awareness
(Blake, Tadin, Sobel, Raissian & Chong, 2006). This is further supported by lesion and inactivation studies (Tong, 2003).
These observations are further supported by single-neuron studies. Single-cell recordings in the lateral geniculate nucleus (LGN) and area 17 of the cat brain indicate that switches in perceptual dominance during binocular rivalry depend on
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inter-ocular interactions at the level of binocular neurons of the primary visual cortex
(Sengpiel, Blakemore & Harrad, 1995). It is likely that inter-ocular suppression is directly related to the functional architecture of V1 (interactions between neighbouring cortical columns) (Sengpiel, Bonhoeffer, Freeman & Blakemore,
2001). This pattern is also observed in human studies (de Labra & Valle-Inclan,
2001). Dominance of one image over the other is thought to result from small activity differences between channels in the low-level visual cortex (Freeman & Lui,
2009), with the duration of suppression related to the size of the pool of monocular neurons innervated by the suppressed eye, and to the strength of excitation generated by the suppressed stimulus (Blake, 1989). When psychophysical studies using fMRI data are combined, a close association between the dynamics of perception during rivalry and neural events in human primary visual cortex (V1) are observed, supporting eye-rivalry theories (Lee, Blake & Heeger, 2005; Nguyen, Freeman &
Wenderoth, 2001). However, it should be noted that neural activity representing the physical characteristics of a stimulus (sensory neuronal response) does not necessarily imply that those signals contribute to consciousness (Andrews, 2001) as a resultant perceptual image.
1.6.2 Visual-evoked potentials (VEPs) in binocular rivalry
Scalp VEPs can be analysed to identify separate responses from monocular and binocular neurons (Apkarian, Nakayama & Tyler, 1981). Visual-evoked potentials associated with the perceptual shift in rivalry to perceptual dominance occur with a corresponding shift in cortical signals (Brown & Norcia, 1997) that correspond to the time course of activity observed across the retinotopic map in V1 (Valle-Onclan,
Hackley, de Labra & Alvarez, 1999). Dominant patterns produce smaller VEPs early in the visual pathway (70-240 msec), while suppressed patterns produce activity later
Literature Review - Visual Processing in Schizophrenia and Binocular Rivalry 31
(400-700 msec) (Valle-Inclan et al., 1999). Furthermore, when stimuli differ in orientation, evoked related potentials occurred after about 100 ms (Veser et al.,
2008). However when the rival stimuli differ in colour, evoked potentials do not occur until after 200 ms (Veser et al., 2008). This difference suggests that property- dependent cortical networks influence the timing of visual awareness. It is possible that neural events in V1 create an endogenous potential (or rivalry-related potential) that marks the alternation between images (de Labra & Valle-Inclan, 2001). It is proposed that a p300-like wave response is related to the perceptual shift from the dominant to the suppressed pattern (or to piecemeal fusion). This event may mark the breakthrough into awareness of the suppressed eye when attention is captured by the appearance of a new object into the field of view of that eye (Valle-Inclan et al.,
1999).
1.7 Top- down Theories of Binocular Rivalry
Theorists subscribing to ‘top-down’ models of binocular rivalry argue that each image during rivalry is available until the late stages of attentional selection. Thus, binocular rivalry arises from the spontaneous fluctuations in visual attention (Li et al., 2005; Logothetis, 1998; Logotheties et al., 1996). Binocular rivalry involves competition between alternative perceptual interpretations at higher levels of analysis
(Logothetis et al., 1996). Neurons that respond to input from both eyes (binocular) found in higher cortical areas of the visual cortex beyond the primary visual area (Li et al., 2005), are thought to be responsible for the perceptual alternation of images that occurs during binocular rivalry (Li et al., 2005; Logothetis, 1998; Logothetis et al., 1996).
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1.7.1 Single-cell studies.
Evidence to support ‘top-down’ processing also includes the results of single- cell studies. In monkeys trained to respond to perceptions during binocular rivalry
(Logothetis, 1998), correlations between neural activity in many cells of V1, V2 and especially V4 (which are highly populated with binocular cells) and perceptual alternation of the rivalling stimuli during rivalry were observed (Leopold &
Logothetis, 1996). Neural firing within the inferior and superior temporal cortices of monkeys has been interpreted as signalling the change in perception during rivalry, with the associated response by the monkeys indicating recognition of the stimulus image (Sewards & Sewards, 2001). This is likely to be due to the computations made in these same areas (Sewards & Sewards, 2001), where neural activity is thought to reflect the brain's internal view of objects, rather than the effect of the retinal stimulus on cells encoding simple visual features (Sheinberg & Logothetis, 1997).
1.7.2 Imaging studies.
Imaging studies using fMRI have revealed an association between the perceptual alternations during rivalry and frontoparietal cortex activity, thought to play a central role in conscious perception (Lumer, Friston & Rees, 1998). Other associations between cortical activity and the perceptual changes during binocular rivalry have been observed in the visual cortex, medial parietal and left frontal regions using magnetoencephalography (MEG). Co-activation of occipital and frontal regions, including anterior cingulate and medial frontal areas, were apparent when the rival stimulus was dominant (Cosmelli et al., 2004). Tononi and Edelman
(2000) using whole-head MEG measured brain electrical activity by frequency- tagging the opposing flickering stimuli (temporal frequencies of 7 and 12 Hz) during binocular rivalry in healthy subjects. They observed widely-distributed activity in the
Literature Review - Visual Processing in Schizophrenia and Binocular Rivalry 33
frontal, parietal, temporal and occipital areas (Tononi, Srinivasanm Russell &
Edelman, 1998).
When house and face stimuli were presented to different eyes, and responses in the human fusiform face area and parahippocampal place area were measured by fMRI, responses during binocular rivalry were equal in magnitude to those evoked by non-rivalrous stimulus (Tong et al., 1998). This suggests that activity in the fusiform face area and parahippocampal place area reflects the perceived (rather than the retinal) stimulus, and that neural competition during binocular rivalry has been resolved prior to these stages of visual processing (Tong et al., 1998). ‘Top-down’ processing may therefore account for slower binocular rivalry rates in subjects with negative symptoms of schizophrenia observed in response to facial stimuli
(representing four emotional states: happy, sad, angry and neutral) (Yang, Blake &
Park, 2007).
1.7.3 Eye-swapping methodologies.
Investigations incorporating ‘eye swapping’ paradigms into binocular rivalry have further challenged monocular competition (bottom-up) theories (Ngo, Miller,
Liu & Pettigrew, 2000). Eye-swapping paradigms involve presenting opposing images of equal strength to each eye, and periodically swapping them between the two eyes during rivalry (Logothetis et al., 1996). The eye-swapping technique eliminates perceptual alternations during rivalry because the monocular pathways are fatigued (Logothetis et al., 1996). Although opposing stimuli are swapped between the two eyes, images generally stabilise to one eye (Chen & He, 2004), suggesting that the alternation of images is independent of which eye the information originates
(Person & Clifford, 2005). Perceptual alternations are observed as either slow, irregular alternations between images (independent of stimulus swapping) or fast,
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regular alternations that are time-locked to the stimulus alternations (Silver &
Logothetis, 2006). Some authors suggest that inter-ocular suppression accounts for the stabilisation effect, rather than the memory of the stimulus (Chen & He, 2004).
Others argue that the brain combines information across multiple visual features to resolve ambiguities in visual inputs (Silver & Logothetis, 2006).
1.7.4 Neurotransmitter involvement in binocular rivalry.
The observation that pharmacological agents influence binocular rivalry, including ethanol (Donnelly & Miller, 1995), sodium-amytal and caffeine (George,
1936), has prompted researchers to investigate neurotransmitter involvement. The traditional hallucinogenic beverage ‘Ayahuasca’ (Carter et al., 2005; Fercska, White,
& Luna, 2003; Frecska, White et al., 2003) affects binocular rivalry via the active ingredient Psilocybin. This serotoninergic 5HT1A and 5HT2A agonist decreases binocular rivalry rate in a dose-dependent manner, (Carter et al., 2005; Frecska,
White et al., 2003. Psilocybin has been demonstrated to selectively impair motion coherence sensitivity for random-dot patterns. This is likely to be mediated by high- level global motion detectors, but not contrast sensitivity for drifting gratings, believed to be mediated by low-level detectors (Carter et al., 2004). Binocular rivalry rate decreases significantly one-to-two hours after oral ingestion (Carter et al.,
2005; Nagamine, Yishino, Miyazaki, Takahashi & Nomura, 2008), and returns to placebo rates at five to six hours after administration, consistent with the pharmacokinetics of these compounds (Vollenweider, Vollenweider-
Scherpenhuyzen, Babler, Vogel & Hell, 1998; Vollenweider, Vontobel, Hell &
Leenders, 1999). Similar results have been reported using Tandospurone, a 5HT1A agonist (Nagamine et al., 2008).
Literature Review - Visual Processing in Schizophrenia and Binocular Rivalry 35
Gamma-aminobutyric acid (GABA) has been suggested to be involved in binocular rivalry, via suppression of dorsal lateral geniculate nucleus (dLGN) inter- neurons (Bickford et al., 2008). Selective loss of inter-ocular suppression is observed in the presence of the GABA antagonist Bicuculline (Sengpiel &
Vorobyov, 2005). Noradrenaline may also have a role in binocular rivalry as increased pupillary dilation, immediately prior to a switch in perception, reflects levels of noradrenaline released from the locus coeruleus. The locus coeruleus and noradrenaline involvement may be via perceptual selection (Einhauser, Stout, Koch
& Carter, 2008).
1.7.5 Monocular rivalry compared to binocular rivalry.
Monocular rivalry differs to binocular rivalry in that one (or both) eyes can view the two alternative precepts of an image simultaneously. Monocular rivalry may be observed when viewing a bistable image, such as the Necker Cube, Rubin’s
Vase, or Schroder’s Staircase. Each aspect of the image fluctuates in awareness in a rhythmical alternation. It is argued that binocular and monocular rivalry is mediated by a common, high-level mechanism for resolving ambiguity (O’Shea et al., 2009).
However, binocular rivalry is a more automatic, stimulus-driven form of visual competition than rivalry between bistable images, and is less easily biased by selective attention (Meng & Tong, 2004) or voluntary control (van Ee, 2005; vand,
Dam & Brouwer, 2005; van Ee et al., 2006).
1.8 Multi-level or Hierarchical Theories
Recent evidence supports a view of rivalry as a series of processes, each implemented by neural mechanisms at different levels of the visual hierarchy (Blake
& Logothetis, 2002; Pearson & Clifford, 2005) with suppression preceding the synthesis of subjective contours (Sobel & Blake, 2003). This view suggests multiple
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sites of binocular rivalry, each corresponding to analysis of different aspects of the stimuli (Cobo-Lewis et al., 2000). It is proposed that the brain combines information across multiple visual features to resolve ambiguities in visual inputs (Solver &
Logothetis, 2006) at different levels of the visual-processing hierarchy (Pearson,
Tadin & Blake, 2007). Therefore, it is possible that rivalry can operate at both the monocular and binocular levels (Pearson & Clifford, 2004); with both high- and low- level processes being involved in binocular rivalry perception (Carter, Campbell et al., 2004). Connections between V1 and higher areas form functional circuits that are thought to support awareness (Tong, 2003), with synchronisation in cortical neurons being necessary for the establishment of perceptual states and awareness of sensory stimuli (Engel, Fries, Konigm Brecht & Singer, 1999). Tong (2003) noted that damage to V1 disrupts the flow of information to extrastriate areas that are crucial for awareness.
1.8.1 Visual pathway theories of binocular rivalry
1.8.1.1 Monocular and binocular pathways.
The existence of paired monocular and binocular neural pathways that project to dorsal and lateral streams has been the focus of many binocular rivalry researchers. It has been suggested that binocular rivalry suppression occurs at a number of stages along both the monocular and binocular cortical pathways, with suppression increasing as the visual signal progresses along these pathways (Nguyen et al., 2003). Wolfe (1986) suggests these two pathways constitute a ‘rivalry only’ pathway and a ‘stereopsis’ pathway, with the mechanisms responsible for binocular rivalry closely associated with those responsible for stereopsis. Similarly, Barker,
Meese and Summers (2007) conceptualised these two pathways as a ‘within-eye’
(ipsiocular) pathway and a ‘between-eye’ (interocular) pathway, and suggested the
Literature Review - Visual Processing in Schizophrenia and Binocular Rivalry 37
inter-ocular pathway may be a sound candidate for binocular rivalry. It is possible that rivalry can operate at both monocular and binocular levels (Pearson & Clifford,
2004), and that binocular rivalry and stereopsis can coexist at the same spatial location (Blake, Yang & Wilson, 1991). Perhaps binocular rivalry always occurs, even when the two monocular images are identical, but only becomes apparent when the two monocular images differ (Blake et al., 1988). Hence, the perception of one image over the other during binocular rivalry is due to inter-ocular suppression between the two eyes, rather than the memory of the stimulus (Chen & He, 2004).
1.8.1.2 Magnocellular and parvocellular pathways.
Magnocellular and parvocellular neurons originate in the retina and project to the dLGN, forming distinct visual pathways to V1 and beyond (Livingstone &
Hubel, 1987). Livingstone and Hubel (1987) observed that binocular rivalry disappears at very high spatial frequencies. They also noted that two half-images differing in colour but were equal in luminance failed to alternate, and so attributed binocular rivalry to be a function of the magnocellular system. When investigating the cortical components of the Westheimer function (an increment-threshold curve based on a luminance hierarchy, described by Gerald Westheimer, 1965). Yu and
Levi (1997) observed that when a disc presented to one eye and ring to the other flickered experimentally (i.e. were presented under conditions that engage processing of the magnocellular pathways) binocular rivalry resulted. However, when the objects were presented under conditions that engaged processing of the parvocellular pathway (presented continuously), fusion resulted. Further, indirect support of magnocellular processing in binocular rivalry is that binocular rivalry alternation frequency peaks for 3 cpd (Hollins, 1980); the spatial frequency at which the transient (magnocellular) system is most sensitive (Kulikowski & Tolhurst, 1973).
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It is possible that binocular rivalry may be due to interactions higher in the visual cortex within two independent motion channels; one for low velocities (<20
Hz) the dorsal (mainly magnocellular) pathway, and one for higher velocities (>20
Hz) the ventral (manly parvocellular) pathways, rather than between them (van de
Grind, van Hof, van der Smagt & Verstraten, 2001). This is supported by modulations of single-neuron activity in MT (Logothetis & Schall, 1989) that correspond with a state of binocular rivalry (Blake et al., 1998). Another interpretation is that two pathways forming independent binocular interactions between form (V1) and motion (MT) (Andrews & Blakemore, 2002) may be responsible for the alternations of visual stimuli in binocular rivalry.
1.8.2 Inter-hemispheric theory of binocular rivalry.
The inter-hemispheric ‘switching’ hypothesis has been proposed as an alternative model of binocular rivalry (Carter & Pettigrew 2003; Carter et al., 2005;
Miller et al., 2000; Miller et al., 2003; Ngo, 2008; Pettigrew & Miller, 1998). This hypothesis posits that the cortical hemispheres compete for perceptual dominance during rivalry, rather than the competing visual pathways. The inter-hemispheric switching hypothesis suggests that synchronised activation of homologous areas of each cerebral hemisphere alternate, by means of a bistable oscillator circuit that straddles the midline of the ventral tegmentum (Pettigrew, 2001). This oscillator may be responsible for timing aspects of all forms of perceptual rivalry and may be linked to circadian rhythms, despite their different periodicities (Pettigrew & Carter,
2005).
Support for this comes from experiments using cold vestibular stimulation and the application of transmagnetic stimulation to one of the hemispheres during binocular rivalry. Cold vestibular stimulation during binocular rivalry stimulates
Literature Review - Visual Processing in Schizophrenia and Binocular Rivalry 39
shifts of attention (Miller et al., 2000) and increases the predominance of the face stimuli (over other types of stimuli), partially supporting brain imaging lateralisation reports (Miller, 2001). The application of trans-magnetic stimulation to one hemisphere can trigger a switch in stimulus predominance, suggesting that inter- hemispheric switching involves alternating uni-hemispheric attentional selection of neuronal processes for access to visual consciousness (Miller, 2001). This is supported by fMRI studies, during cold-caloric vestibular stimulation (stimulating vestibules by applying cold water to the ear cannel) during rivalry, that indicate perceptual rivalry engages high-level cortical structures that mediate uni-hemispheric attentional selection (Ngo et al., 2008).
Although supporters of the inter-hemispheric switching hypothesis propose that binocular rivalry involves competition between higher cortical processes, there are those that argue that inter-hemispheric involvement may support low-level processing. It has been demonstrated that visual processes similar to rivalry occur in the left and right hemispheres of two split-brain observers, consistent with switching being mediated by low-level processes within each hemisphere (O’Shea & Corballis,
2005a, 2005b). Mechanisms low in the visual system, where the two hemispheres conduct similar analyses of each half of the visual space (O’Shea & Corballis, 2001), compete for perceptual dominance. Faster binocular rivalry rate has been observed when stimuli were presented to the right visual field rather than the left, suggesting the rivalry may be driven by retinotopically-local processes; visual analysis in the left hemisphere may be faster in right-handed people (Chen & He, 2003). Trans- magnetic stimulation during binocular rivalry has also been observed to effect retinotopic processes, suggesting that binocular rivalry mechanisms are reliant on neural activity early in the visual pathway (Pearson et al., 2007), and that the
40 Literature Review - Visual Processing in Schizophrenia and Binocular Rivalry
temporal dynamics during rivalry are likely to be local and hemisphere-specific processes (He, Carlson & Chen, 2005).
1.9 Summary and introduction to Chapters
This chapter has explored the literature surrounding visual abnormalities that contribute to visual processing deficits and cognitive disturbances in schizophrenia, the contemporary theories of binocular rivalry, and the effects of altering stimuli with respect to movement, colour, spatial frequency and luminance binocular rivalry. It is apparent that although binocular rivalry has been intensively investigated, and much is known regarding the physical characteristics that modify binocular rivalry, much has been left unexplained. Binocular rivalry provides a unique opportunity to explore visual processes and visual perception, and provides a promising tool to investigate neurological and mental illness. There are only a few studies that investigate binocular rivalry in schizophrenia. The limited research available is contradictory, with some claiming slower binocular rivalry rates (Fox, 1965;
Sappenfield & Ripke, 1961) and others showing no differences (Miller et al., 2003).
The research presented in this Thesis seeks to resolve this discrepancy.
There are many methods of collecting binocular rivalry data. For this study the binocular rivalry method of Pettigrew and Miller (1998) was selected as it had a number of advantages over other methods. This method had previously been demonstrated to reliably collect binocular rivalry data in individuals with mental illness, providing some comparison data. The characteristic alternation of opposing perceptual images is easily achieved with minimal training and without the need for individuals to fix their gaze on a central point. This method allows the stimuli to be manipulated with respect to colour, luminance, movement and spatial frequency to investigate specific parts of the visual system.
Literature Review - Visual Processing in Schizophrenia and Binocular Rivalry 41
The selection of the method provides a natural starting point for this research.
Pettigrew and Miller (1998) and Miller et al., (2003) investigated binocular rivalry in groups of participants with mental illness and controls using two stimulus conditions.
Miller et al., (2003) investigated participants with bipolar disorder, depression, schizophrenia and controls using low-strength stimuli (stationary, 4 cpd horizontal and vertical monochromatic lines of 90% luminance contrast). These authors compared their data with data provided in Pettigrew and Miller (1998) from participants with bipolar disorder and controls using a high-strength stimulus
(monochromatic 8 cpd vertical and horizontal lines of moving at approximately 4 cps). They noted that alterations to the strength of the stimuli effected binocular rivalry rate. Because these comparisons were between different groups it is not clear what the effect of increasing the stimuli strength would have on individuals using this method of binocular rivalry. The investigation in the next chapter (Chapter 2) explores this issue.
In Chapter 2, the binocular rivalry stimulus is manipulated to produce horizontal and vertical lines that vary in their presentation with respect to colour, movement, spatial frequency and luminance. Stimuli are presented in two colour conditions (red/black), two temporal conditions (moving or stationary), two spatial frequency conditions (4 cpd and 8 cpd) and two luminance conditions (low and high) to investigate stimulus effects in binocular rivalry. A total of 16 stimulus conditions are tested; two being the same as those reported in Pettigrew and Miller (1998) and
Miller et al., (2003). Stimulus effects are investigated in a group of twenty participants with no mental illness using a 2X2X2X2 repeat within-group design. In this chapter the ‘inter-hemispheric switch’ hypothesis of binocular rivalry proposed by these authors is also investigated.
42 Literature Review - Visual Processing in Schizophrenia and Binocular Rivalry
The disadvantage of the Pettigrew and Miller’s method of binocular rivalry is that the computer software only allows one image to be presented on the computer screen. There is no way to adjust the stimuli so that a different stimulus can be presented to each eye. Thus, opposing orientation of lines (vertical and horizontal) is the only ‘between eye’ difference that can be achieved. Other methods of binocular rivalry that use stereoscopes or alternative computer methods allow stimuli different in colour, spatial frequency, temporal frequency or luminance to be presented independently to the left and right eyes. This allows the researcher to investigate the effect that the stimulus presented to one eye has on dominance and suppression that occurs during binocular rivalry. Many researchers in recent times have taken advantage of this feature to explore the neural events that occur in binocular rivalry and reported their data in terms of Levelt’s second proposition. Although it is not possible to test Levelt’s second proposition, Levelt’s fourth proposition that
“increasing the stimulus strength in both eyes will increase the alternation frequency” can be tested using in a variety of stimulus conditions. This allows confidence in the validity of the results.
Pettigrew and Miller and colleagues have proposed that slow binocular rivalry rate is a trait maker for bipolar disorder and may be an important tool for diagnosis
(see Pettigrew and Miller, 1998 and Miller et al., 2003). However, there are little data to support this claim, and little support is provided by perceptual rivalry studies.
Krug, Brunskill, Scarna, Goodwin & Parker (2008) refute this claim with respect to bistable figures. There are only three studies that have investigated classical binocular rivalry in schizophrenia (Fox, 1965, Miller et al., 2003, Sappenfield &
Ripke, 1961). In order to support Pettigrew and Miller’s claim that slow binocular
Literature Review - Visual Processing in Schizophrenia and Binocular Rivalry 43
rivalry is a trait marker for bipolar disorder, there is a need to demonstrate that slow binocular rivalry is not present in schizophrenia.
Miller et al., (2003) investigated binocular rivalry in schizophrenia using stationary, 4 cpd horizontal and vertical monochromatic lines of 90% luminance contrast in participants who had bipolar disorder, depression or schizophrenia and controls. They reported no difference in binocular rivalry rate in participants with schizophrenia compared to controls which is contrary to previous reports (Fox, 1965;
Pettigrew & Miller, 1998; Sappenfield & Pike, 1961; White et al., 2001). They then compared their data with that provided in Pettigrew and Miller (1998) and with other published data relating to perceptual rivalry. Participants with schizophrenia were only tested in one stimulus condition using the binocular rivalry method of Pettigrew and Miller. In order to extend this work and to settle this discrepancy in the literature, binocular rivalry is investigated in the current study in participants with schizophrenia and controls using a ‘within group’ design. This design employs low and high strength stimuli and a perceptual rivalry task; the Necker cube, a task frequently reported in the schizophrenia literature.
As previously noted, individuals with schizophrenia experience both subjective sensory anomalies and objective deficits of sensory function (Brenner, Krishnan &
Vohs et al., 2009) that contribute to many of the symptoms of the disease. They have marked deficits in visual processing that contribute to perceptual abnormalities, hallucination and the misinterpretation of perceptual information associated with delusions. Individuals with schizophrenia have delayed or interrupted visual processing that may account for many of the negative symptoms, such as poverty of thought and speech, and decreased reaction to the immediate surrounding environment (Cadenhead, Geyer, Butler, Perry, Sprock & Braff, 1997; Uhlhaas,
44 Literature Review - Visual Processing in Schizophrenia and Binocular Rivalry
Phillips & Silverstein, 2005). Over-active magnocellular pathways correlate with poor selective attention, poor concentration, heightened awareness of background noise and distractibility in individuals with schizophrenia (Hetrick, Erickson, &
Smith, 2010). It is suggested that tasks that combine contrast sensitivity to magnocellular versus parvocellular biased stimuli may be useful in future schizophrenia research (Green & Butler, 2009). In section 1.8.1.2 it is noted that the contribution that magnocellular and parvocellular visual pathways have been investigated in binocular rivalry, with one (Livingstone & Hubel, 1987) or both of these systems implicated in initiating perceptual alternations (Yu & Levi, 1997).
However the research in this area is scant. Binocular rivalry stimuli that bias the magnocellular and parvocellular visual pathways can be achieved by modifying the stimuli presented to each with respect to luminance contrast, movement, colour and spatial frequency. This provides a unique opportunity to explore magnocellular and parvocellular processing in participants with schizophrenia and controls using two binocular rivalry tasks, one to bias the magnocellular and the other the parvocellular visual pathways in Chapter 4.
An inter-hemispheric model of binocular rivalry has been proposed that suggests binocular rivalry is the result of competition between the two cortical hemispheres that occurs by virtue of an ‘inter-hemispheric switching’ mechanism
(Pettigrew & Miller, 1998). Individuals with schizophrenia deficits in spatial perception and attention related to right hemisphere functioning (O'Donnell, Potts et al., 2002) and deficits associated with the transfer verbal information from the right to the left hemisphere via the corpus callosum (Endrass, Mohr et al., 2002). To investigate whether abnormal right hemisphere functioning has an effect on binocular rivalry, binocular rivalry rates recorded by participants with schizophrenia
Literature Review - Visual Processing in Schizophrenia and Binocular Rivalry 45
are compared to the Benton’s Judgment of Line Orientation (BJLO) task (Benton,
Varney & Hamsher, 1978); the BJLO task is widely accepted to be processed within the right cortical hemisphere in Chapter 5.
One of the limitations to researching schizophrenia is most individuals are taking at least one antipsychotic medication. For clinical diagnosis of schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders – Edition 4
(DSM-IV) criteria to be determined, a six-month trial period of an antipsychotic medication with improvement in symptoms is needed. This makes an investigation into the role of dopamine in binocular rivalry difficult as antipsychotic medications block dopamine receptors; in particular the dopamine D2 receptor (Javitt, 2009).
Additionally, many hospital human research ethics committees are reluctant to allow medications to be withheld from individuals with schizophrenia as they are likely to experience return of symptoms and a reduction in long term cognitive functioning.
This restricts to investigations in medicated individuals or in un-medicated individuals in the prodromal phase of schizophrenia; that is, the period before a definite diagnosis is established. These challenges require novel approaches to the investigation of neurotransmitter involvement in neural visual processing in medicated participants.
Given that D2 receptors within the visual system play an important role in visual functioning, and that schizophrenia has been associated with abnormal D2 receptor density and functioning, it is plausible to examine visual processing according to genetic variations in D2 receptors. The TaqI A of dopamine D2 receptor (DRD2) gene is a commonly-investigated genetic locus in schizophrenia
(Behravan, Hemayatkar, Toufani & Abdollahian, 2008). Carriers of the A1 allele of the Taq1 of dopamine D2 receptor (DRD2) gene polymorphisms (A1+ individuals
46 Literature Review - Visual Processing in Schizophrenia and Binocular Rivalry
with A1/A1 or A1/A2 genotypes) typically have a lowered DRD2 density and diminished function of DRD2 in the striatum, (Kondo, Mihara, Suzuki, Yasui-
Furukori & Kaneko, 2003; Mihara, Kondo et al., 2000; Noble, 2000). The presence of the A1 allele of the DRD2 receptor gene, and thus the distribution of dopamine receptors and dopamine function, offers a non-invasive and novel approach to investigating dopamine involvement in binocular rivalry, explored in the final study
(Chapter 6).
Literature Review - Visual Processing in Schizophrenia and Binocular Rivalry 47
Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and
Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry
2.1 Binocular rivalry
2.1.1 Binocular rivalry rate.
Binocular rivalry rates are stable within individuals over time. High correlations (above r = 0.8) are evident in binocular rivalry rates recorded weeks, or years, after the initial test using the same stimulus (Miller et al., 2003, Pettigrew &
Miller, 1998; Pettigrew & Carter, 2005). Large between-individuals differences in binocular rivalry rates have been reported by a number of authors (Carter et al.,
2005; Leat & Woodhouse, 1987, Miller et al., 2003; Pettigrew, 2001; Ukai, Ando &
Kuze, 2003), indicating that binocular rivalry rate may be determined by an endogenously-driven individual characteristic.
It has been suggested that the less-frequently investigated binocular rivalry rate, a measure of the rhythmical alternation between rivalling stimuli, reflects an inextricable component of all forms of visual perception (Pettigrew & Carter, 2005).
Therefore, rate can be considered a key feature of the binocular rivalry phenomenon.
Pettigrew and Miller (1998) suggest that individuals have an endogenous ‘switch rate’ or an internal rhythm of perceptual oscillations that remains fairly constant for an individual, however may be modifiable by alterations made to the strength of the stimulus. Pettigrew and Miller propose that a switching mechanism, located outside the visual system, regulates binocular rivalry rate and rhythm. This model predicts that individuals who have a faster endogenous ‘switch rate’ (‘fast switchers’) will demonstrate more rapid perceptual alternations than ‘slow switchers’. Furthermore, as the strength of the stimulus increases, perceptual alternations for ‘fast switchers’
Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry 49
will increase at a more rapid rate than that seen in ‘slow switchers’. Pettigrew (2001) provides a representation of this model as a figure, but provides no empirical data.
As noted in Chapter 1, binocular rivalry is significantly influenced by the stimuli used. Subtle changes in the characteristics of the binocular rivalry stimulus can produce large variations in binocular rivalry rates. Increasing stimulus strength, achieved by increasing the luminance contrast, spatial frequency, colour and temporal frequency of the competing stimuli (Breese, 1899; Levelt, 1968) subsequently increases binocular rivalry rate (Fahle, 1982; O’Shea & Williams,
1996; O’Shea et al., 1997; Rogers, Rogers & Tootle, 1977).
Alternation of images is more rapid, and thus dominance durations are reduced, when the stimuli presented to each eye vary greatly in terms of luminance contrast
(Mueller & Blake, 1989; Whittle, 1965), velocity (Blake, Aimba & Williams, 1985), colour (Hong & Shevell, 2006; Rogers & Hollins, 1982; Wade, 1976), and spatial frequency (Fahle, 1982; Wade, 1976). Presenting conflicting rival stimuli of different strengths is appropriate when examining the effect of stimulus characteristics on suppression (or dominance) of one eye’s perceptual image over the other. However, this may not be the case when the rate or frequency of perceptual alternations is of primary importance. Experimental evidence of binocular rivalry rate is generally reliant on the examination of dominance duration, or exclusive visibility of the competing stimuli, rather than a measure of alternation frequency (Hollins, 1980;
Mueller & Blake, 1989; O’Shea et al., 1997, Whittle, 1965).
To investigate the possibility that binocular rivalry rate is regulated by an intrinsic rhythm or endogenous ‘switching mechanism’ located outside the visual system, care must be taken in selecting the binocular rivalry stimuli. Experimental methods allow binocular rivalry data to be collected in conditions where the stimuli
50 Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry
presented to each eye are equal, to ensure the visual system is not biased to observe one image over the other. Levelt (1968) suggests that when conflicting stimuli are presented to each eye equally (in terms of stimulus strength, the rate of alternations recorded using a two-choice paradigm, and assuming all other things being equal) the time spent viewing the right-eye (Tr) image will be equal to that spent viewing the left-eye image (Tl), (so Tr = Tl) with the only effect on Tr or Tl being eye dominance. In his fourth proposition, Levelt concluded that an, “increase of the stimulus strength in both eyes will increase the alternation frequency” (Levelt, 1968: page 76). Levelt defined ‘stimulus strength’ as the, “Amount of contour per area, and for a constant amount of contour per area, the strength of those contours.”
Examining binocular rivalry rate using Levelt’s fourth proposition is therefore appropriate to test the hypothesis of Pettigrew’s model, as this hypothesis assumes that the oscillations occur between two stimuli of equal strength, with no inherent bias. Collecting binocular rivalry data using the method by Pettigrew and Miller
(1998) presents stimuli of equal strength to each eye, with the orientation of the lines being the only difference.
There are only a small number of studies in the binocular rivalry literature that investigate the effect of increasing the strength of the stimuli presented to each eye equally, and therefore Levelt’s fourth proposition. Alexander demonstrated that
‘stronger’ images will alternate more rapidly than ‘weaker’ images using two conditions of stimulus strength, broken versus continuous contour, and greater or lesser contrast between figure and ground (Alexander, 1951). However, luminance levels and spatial frequency were not quantified. In a later experiment, Hollins
(1980) demonstrated that exclusive visibility increases as contrast increases equally in both eyes; however this significant difference was only seen for one participant.
Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry 51
In an earlier classic study Breese, using red gratings presented to one eye and green gratings to the other, demonstrated that binocular rivalry rate increased when luminance levels were increased from low-intensity light to the brightest intensity
(without dazzle) by the same amount in both eyes (Breese, 1899). Once more, luminance levels were not quantified, and green gratings were present to one eye while red gratings were presented to the other adding a colour confound. None of these studies are recent and provide minimal data to support Levelt’s fourth proposition, and provide insufficient quantifiable data to assess Pettigrew’s hypothesis.
2.1.2 Dominance durations.
The distribution of perceptual dominance durations produced during binocular rivalry tend to be right-skewed. More predictable distributions allow researchers a greater opportunity to examine the relationship between perceptual awareness and neural function. It has been widely reported that frequency histograms of perceptual dominance durations during binocular rivalry approximate a gamma-density function
(Borsellino, De Marco, Allazetta, Rinesi & Bartolini, 1972; Carter & Pettigrew;
2003; De Marco et al., 1977, Levelt, 1968; Logothetis et al., 1996, Miller et al.,
2003; Pettigrew & Miller, 1998; Van Ee et al., 2006). Histograms of perceptual dominance durations are proposed to fit a gamma distribution more adequately when there are greater than 150 alternations/time periods recorded (Brascamp et al., 2006).
Thus, better fit would theoretically be achieved with high-strength stimuli, rather than low-strength stimuli. However, there are a number of authors who have failed to fit empirical data to the gamma distribution (Brascamp et al., 2005; Cogna, 1973;
Zhou et al., 2004), making this assertion controversial. Testing this proposition and that of Pettigrew and colleagues, with empirical data may allow us the opportunity to
52 Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry
investigate the interaction between stimulus characteristics and individual variability in binocular rivalry. Mapping dominance durations, as a behavioural measure of neural activity in participants with schizophrenia and controls, may provide a greater understanding of the neural processes involved in the perceptual disturbances attributed to this disorder.
2.2 Study 1
2.2.1 Aims.
The first aim of this study was to determine if increasing the strength of rivalling stimuli (vertical and horizontal gratings of equal strength) in terms of luminance, spatial frequency, colour or movement increased the rate of binocular rivalry alternation in a group of 20 healthy participants. The second aim was to determine whether binocular rivalry alternations increase to a greater extent in ‘fast alternators’ than in ‘slow alternators’ using the binocular rivalry method used by
Pettigrew and Miller (1998) and Miller et al., (2003). A third aim was to determine whether the perceptual dominance durations of fast alternators would more readily fit a gamma distribution than those produced by slower alternators, when the gamma distribution is defined as f(x) = λr / Г(r) xr-1exp (-λx), where Г(r) = (r-1)!
2.2.2 Hypotheses.
The hypotheses tested were:
Increasing the stimulus strength of binocular rivalry stimuli
subsequently increases binocular rivalry rates. Furthermore, these
increases are greater in ‘fast binocular rivalry alternators’ compared to
‘slow binocular rivalry alternators’;
Histograms of perceptual dominance durations derived from faster
alternators would approximate a gamma distribution.
Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry 53
2.3 Method
Before commencing the study, a power analysis was performed to determine the minimum number of participants required to reject the null hypothesis that,
“Increasing stimulus strength (by increasing spatial frequency, luminance, movement and colour) does not increase binocular rivalry rate.” The published binocular rivalry rates reported in healthy participants by Miller et al., (2003) were entered into the
G*power3 program (Faul & Erdfelder, 1992). It was estimated that a sample size of
20 individuals was required for a two-sided 5% significance level and power of 80 to produce an overall effect.
2.3.1 Participants.
Twenty healthy volunteers, who were screened to exclude neuropsychiatric disease with the Structured Clinical Interview for the DSM-IV (SCID), were recruited. Four participants were male, and 16 were female. The age range was 22-
64 years (M = 39.8, SD = 12.97). All participants were right-handed, as assessed using the Annett Handed Questionnaire (Annett, 1970). All participants had normal vision (that is, were free from strabismus, astigmatism or eye disease) and 6/6 visual acuity (corrected or uncorrected) in each eye as assessed by Snellen visual acuity testing. All participants had normal vision and at least 6/9 visual acuity (corrected or uncorrected) in each eye assessed by the Snellen visual acuity testing. To reduce any eye dominance effect related to inter-ocular differences in visual acuity, participants were excluded from the study if visual acuity in each eye was not equal (to within two letters). In addition, each participant undertook a keyhole task to determine sighting eye dominance as described in (Osburn & Klingsporn, 1998).
Written informed consent was provided by each participant prior to the commencement of testing. Ethical clearance was obtained from the Royal Brisbane
54 Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry
and Women’s Hospital Human Research Ethics Committee, and the Queensland
University of Technology Human Research Ethics Committee. Binocular rivalry testing took place at an outpatient facility of the Royal Brisbane and Women’s
Hospital and in the Optometry Clinic at the Queensland University of Technology.
2.3.2 Apparatus.
2.3.2.1 Binocular rivalry stimuli.
The binocular rivalry stimuli were presented as a stationary, circular-grid target, subtending 1.5 of visual angle, generated on a personal computer monitor using BRtestTM software (BiReme Pty Ltd. Brisbane, Australia). The grid was achieved by rapidly alternating the two rivalling stimuli (vertical and horizontal square wave gratings) at 120 Hz (this methodology reduces any Troxler effect; see
(Blake, 2005; Levelt, 1968). The grid was viewed from a distance of three metres through liquid crystal shutter goggles (NuVisionTM60GX, MacNaughton, Canada).
This system of collecting binocular rivalry data presents horizontal and vertical line stimuli (square wave gratings) of equal strength to each eye with respect to contour, luminance, movement and colour, in the same retinal location with minimal crosstalk; the only difference being the orientation of the lines. The use of liquid crystal glasses eliminated the need for fixation, and thus required minimal instruction allowing completely näive participants to experience binocular rivalry and accurately record their precepts. Additionally, the researcher could manipulate the presentation of vertical and horizontal lines to either the left or right eye without the participant being aware, allowing orientation of the lines to be counter-balanced across participants and stimulus conditions. This eliminates any potential effects of eye dominance or vertical/horizontal preference.
Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry 55
Luminance and chromaticity levels were measured at a distance of three metres through the shutter goggles (NuVisionTM60GX , MacNaughton, Canada) by a luminance colourimeter (model BM-7, Topcon, Japan). The maximum luminance condition was determined by the maximum luminance capability of the computer monitor, with luminance levels measured through the goggles being 60% less than without the goggles. This limited the maximum actual test luminance, and the range over which luminance could be varied. Average luminance of each stimulus was calculated as Lmax+Lmin/2. Lmax and Lmin were measured through the shutter goggles using a 0.2 field to ensure that the black and red/white bars were measured independently. However, because the 0.2 field covered the entire diameter of the target bar in the 8 cpd conditions but not in the 4 cpd conditions, slight variations in the measurements occurred, however these were small (< 0.4 cd/m2) and therefore the average was taken. Luminance levels for the high-luminance condition were
(Lmax) 9.6 – 10.0cd/m2 and (Lmin) 1.6–1.7 cd/m2. Luminance levels for the low- luminance condition were (Lmax) 1.9 – 2.2 cd/m2 and (Lmin) 1.4– 1.6 cd/m2.
Average luminance for low-luminance stimuli was 1.6cd/m2, and in the high luminance stimuli 5.8 cd/m2. Luminance contrast was calculated using Michelson’s formula, (Lmax-Lmin)/(Lmax +Lmin); 15% for the low- and 68% for high-contrast conditions in both the red/black and white/black conditions. For consistency, reported luminance levels were measured from the centre of the field for the vertical grating. Cross-talk between the goggle lenses was minimal. Lmax was <0.01 cd/m2 when the vertical lines were measured through the horizontal shutter lens (and vice versa).
To measure the effect of ‘colour’ and achieve equal-strength coloured stimuli presented to each eye, vertical and horizontal monochromatic lines were presented
56 Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry
on the same background (consistent with (Carter & Pettigrew, 2003; Miller et al.,
2003; Pettigrew & Miller, 1998). White/black versus red/black gratings were chosen
(white stimulating all cones, and therefore theoretically ‘stronger’ than red gratings that stimulate only medium- and long-wavelength cones). The chromaticity recordings were consistent for the red and white bars in all stimulus conditions; white achromatic gratings (x= 0.3102, y= 0.3307) and red chromatic gratings (x= 0.6181, y= 0.3251). Chromaticity measures reported here were without the goggles, as recordings through the lenses could not be achieved.
Moving 4 cycles per second (c/s) versus not moving (stationary, 0 c/s) stimuli were selected to insure comparison of two discrete groups of stimuli; stationary or not moving with moving stimuli. Ideally, the rivalling stimuli should be presented at two different temporal speeds (for example, 2 c/s versus 4 c/s). However, because stimuli are also presented at two different spatial frequencies (4 cpd and 8 cpd), movement/spatial frequency confound is introduced. Stimuli of 4 cpd and 8 cpd appear to move at different speeds when temporally modulated at 2 c/s, as do 4 cpd and 8 cpd stimuli modulated at 4 c/s. It could not be determined with any certainty that stimuli moving at 4 c/s were moving faster, and therefore produced increased stimulus strength, than at 2 c/s when using stimuli of two different spatial frequencies. The moving stimuli were presented at 4 c/s. This was calculated by counting the number of cycles (one light and dark bar comprising one cycle) that crossed the side of the stimulus aperture in 10 seconds. One cycle measured 0.25 cpd for the 4 cpd stimuli and 0.125 cpd for the 8 cpd stimuli.
This study provides a number of methodological improvements over previous classical studies of binocular rivalry. The binocular rivalry method allowed the manipulation of luminance contrast, spatial frequency, temporal frequency and
Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry 57
colour of the binocular rivalry stimuli, while ensuring that the strength of stimuli presented to each eye remained equal, with the orientation of the lines being the only difference. This ensured that Levelt’s fourth proposition was able to be tested, and
Pettigrew’s model explored.
2.4 Design
Binocular rivalry data were collected using a 2X2X2X2 (luminance, spatial frequency, chromicity, movement) repeat design. Two luminance conditions
(lower= 1.6 cd/m2, and higher= 5.8 cd/m2), spatial frequencies (4 cpd and 8 cpd), chromatic conditions (white bars [x= 0.3102, y= 0.3307] on black background and red bars [x=0.6181, y=0.3251] on a black background) and movement conditions
(stationary and temporally modulated moving stimuli, 4 c/s) were included. To ensure that all participants experienced optimal binocular rivalry and avoided binocular fusion, stimuli conditions were chosen well within the binocular rivalry threshold (being where greater than 50% of participants perceived binocular rivalry for greater than 50% of the time). Binocular fusion can occur at spatial frequencies below 2 cpd (Liu et al., 1992) and above 10 cpd (Livingstone & Hubel, 1987), and at low luminance contrast (Hong & Shevell, 2006; Liu et al., 1992). Each participant completed sixteen two-minute blocks of binocular rivalry measurements. To ensure test order did not influence binocular rivalry, the order of binocular rivalry tasks were counterbalanced with respect to spatial frequency, luminance, colour and movement.
To compare ‘fast’ with ‘slow’ alternators, individuals were grouped according to their mean binocular rivalry rates, and considered either ‘fast’ or ‘slow alternators’ when more than 50% of their mean binocular rivalry rates fell within the either the top or bottom quartile over the 16 stimulus conditions.
58 Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry
2.5 Procedure
Testing took place in dimly lit room (40 lux). Participants were adapted to the luminance conditions of the binocular rivalry tasks for five minutes, and completed the low-luminance tasks before completing the high-luminance binocular rivalry tasks. Participants were seated three metres from the computer screen with the goggles in place.
They were asked to record binocular rivalry alternations, by pushing a key on a response keypad, when each image was exclusively dominant (when the image comprised only vertical or horizontal lines). This method produces a forced two- choice paradigm consistent with Levelt’s alternation model (1968), where time spent viewing the right-eye (Tr) image will be equal to time spent viewing the left-eye image (Tl), (so Tr = Tl), with the only effect on Tr or Tl being eye dominance.
Although in a two-choice forced paradigm the inclusion of mixed images inflates the period that either the vertical or horizontal image is perceived, this has no effect on binocular rivalry alternation rate (Blake, 2005; Kovacs & Eisenberg, 2005).
A small experiment was conducted in a subgroup of participants (n = 10) prior to the main study to compare the accuracy of recording binocular rivalry using a two- and three-choice paradigm using moving and stationary stimuli. A binocular rivalry simulation task was developed and presented to ten participants (two males and eight females) on a personal computer. The two-button task generally produced more accurate responses than the three-button task (96.5% and 91% correct, respectively) and seven out of the ten participants reported the two-button task as less confusing.
The frequency of alternations (referred from here on as binocular rivalry rate) was calculated by dividing the number of button pushes by the total time of rivalry,
Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry 59
and was reported in Hertz (Hz). The period between button pushes (from here on referred as to as ‘dominance durations’) was measured and recorded in milliseconds.
2.6 Statistical Analyses
2.6.1 Two-sided Smirnov test to compare dominance duration distributions.
To determine the difference between dominance duration distributions produced by slow and fast alternators, and therefore the likelihood of individual variations that may contribute to binocular rivalry rate, a two-sided Smirnov test was conducted for each condition. The data consisted of two independent random samples, one of size n, X1, X2 …. Xn (slow alternators) and the other of size m, Y1,
Y2, …. Ym (fast alternators). If F(x) and G(x) represent the unknown, distribution functions of slow and fast alternators respectively, the hypotheses for a two-sided test would be;
H0 :F(x) = G(x) for all x from - ∞ to + ∞.
H1 : F(x) ≠ G(x) for at least one value of x.
To calculate the test statistic S1 (x) is the empirical distribution function based on the random sample X1, X2 …. Xn, and S2 (x) is the empirical distribution function based on the other random sample Y1, Y2, …. Ym. The test statistic, T1, is the greatest vertical distance between the two empirical distribution functions.
T1 = sup /S1 (x) – S2 (x)/ x.
The decision rule, to reject H0 at the level significance α is if T1 exceeds its 1
– α quantile. For large samples (where n and m > 20) the 0.95 quantile of T1 is given by w0.95 ≈1.36√ m+n/ mn (Conover, 1971).
60 Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry
2.7 Results
2.7.1 Binocular rivalry rate.
Binocular rivalry rates were normally distributed so parametric analyses were used. Test conditions included two levels of luminance (lower and higher), stationary and moving, two spatial frequencies (4 cpd and 8 cpd), and achromatic
(white) and chromatic (red) bars. Individual differences in mean binocular rivalry rates recorded across the 16 stimulus conditions ranged from 0.26 Hz to 0.89 Hz.
The slowest individual binocular rivalry rate (0.11 Hz) was recorded using the stationary 8 cpd coloured stimuli of low luminance, while the fastest individual binocular rivalry rate (1.32 Hz) was recorded using the achromatic, stationary, and high-luminance 8 cpd stimulus.
Figure 2.1 shows binocular rivalry rates for each participant across the 16 stimulus conditions. Examination of Figure 2.1 shows that altering the binocular rivalry stimuli characteristic affects binocular rivalry rate more in some participants than seen in others. For example, participant six (M = 0.321 Hz, SD = 0.042 Hz, min 0.27 Hz, max 0.42 Hz, range 0.15 Hz) contrasts with participant 13 (M = 0.901
Hz, SD = 0.247 Hz, min 0.43 Hz, max 1.32 Hz, range 0.89 Hz).
Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry 61
Individual Differences in Binocular Rivalry Rates
1.4
1.2
1
0.8
0.6
0.4
Binocular rivalry ratein Hertz 0.2
0 1234567891011121314151617181920 Participants
L4AS L4AM L4CS L4CM L8AS L8AM L8CS L8CM H4A S H4A M H4CS H4CM H8A S H8A M H8CS H8CM
Figure 2.1: Binocular rivalry rates by 20 participants across all stimulus conditions (n = 16). Dashed line represents the mean binocular rate (M = 0.463Hz) for all stimulus conditions across all subjects. Legend shows stimulus condition (L= low luminance, H= high luminance, 4= 4 cpd, 8= 8cpd, A= achromatic [white], C= chromatic [red], M= moving and S= stationary).
In general, all stimuli presented at higher luminance (5.8 cd/m2) produced faster mean binocular rivalry rates (M= 0.548 Hz, SD = 0.357 Hz), ranging from 0.49
Hz to 0.61 Hz, than those of lower luminance (1.6 cd/m2), (M= 0.376 Hz, SD = 0.057
Hz), with a range of 0.3 Hz to 0.46 Hz. Changing the binocular rivalry stimulus condition affected the binocular rivalry rate to varying degrees in each participant.
Participant three recorded the lowest mean binocular rivalry rate of 0.235 Hz, participant 10 the highest (0.995 Hz) while participant six demonstrated the smallest range of binocular rivalry rates (range 0.15 Hz) and participant 13 the greatest (0.89
Hz). Moving stimuli (4 c/s) tended to produce faster mean binocular rivalry rates (M
=0.498 Hz, SD = 0.084 Hz) than stationary stimuli (M = 0.426 Hz, SD = 0.106 Hz) in both high- and low-luminance conditions, with high-luminance moving stimuli producing faster binocular rivalry rates (0.55 Hz to 0.61 Hz) compared with
62 Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry
stationary stimuli (0.49 Hz to 0.55 Hz). Mean binocular rivalry rates across the 16 stimulus conditions are shown in Figure 2.2.
To ensure that the low- and high-stimulus strength conditions produced a difference in binocular rivalry rates and were appropriate to test the hypotheses, repeated measures ANOVA was performed. Repeated measures ANOVA revealed that luminance and movement had a significant main effect on binocular rivalry rate,
(F[16,19] = 60.571, p < .001 and F[16,19] = 18.692, p < .001, respectively) and that spatial frequency and colour had no effect on binocular rivalry rate (F[16,19] =
1.015, p = .326 and F[16,19]=0.82, p = .377 respectively). As declines in the visual system may occur with age, age was added as a covariate, the significant main effect for movement remained (F(1,18) = 18.677, p < .001), but was reduced to a trend for luminance contrast (F(1,18) = 4.188, p = .056). Gender, eye dominance and handedness showed no effect (p > .05).
1.00
0.90
0.80
0.70
z 0.60
0.50
0.40 BR Rate in H Rate in BR
0.30
0.20
0.10
0.00 4cpd/White 4cpd/Red 8cpd/White 8cpd/Red 4cpd/White 4cpd/Red 8cpd/White 8cpd/Red
Stationary Moving
Low Luminance High Luminance
Figure 2.2: Mean binocular rivalry rates (n = 20) across the 16 stimulus conditions. Note: Error bars show standard error.
Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry 63
Normalised dominance durations (time periods between button pushes, measured in milliseconds expressed as fractions of their means), approximated a gamma-density function (Carter & Pettigrew, 2003; Logothetis et al., 1996, Miller et al., 2003). When histograms of the normalised dominance durations of the 16 stimulus conditions were drawn, typical right-skewed distributions resulted. To determine whether these empirical binocular rivalry data approximated a gamma- density function, a one-sample Kolmogorov-Smirnov goodness-of-fit test was performed against the normalised dominance durations for each of the 16 stimulus conditions, using the Statistical Analysis System (SAS®) computer software. Only one of the 16 stimulus conditions (the stationary, low-luminance, achromatic of 4 c/d condition) demonstrated an acceptable fit to the gamma density function
(Kolmogorov-Smirnov D = 0.0288, p = .140). The other conditions demonstrated an unacceptable fit (p < .05) to the gamma-density function (a p value of greater than
.05, demonstrating a good fit).
2.7.2 Fast versus slow alternators (binocular rivalry rate).
Because colour and spatial frequency did not have a significant main effect on binocular rivalry rate, mean binocular rivalry rates calculated from the original analyses were averaged across the conditions of colour and spatial frequency, leaving luminance and movement. A second analysis was then performed to determine whether participants who had slower binocular rivalry alternations (‘slow alternators’) were less affected by changes to stimulus conditions compared to those with faster binocular rivalry alternations (‘fast alternators’), as proposed by Pettigrew
(2001). The mean binocular rivalry rate of the 320 trials (20 participants x 16 conditions) was 0.41 Hz. ‘Fast alternators’ (n = 3) were those who recorded binocular rivalry rates within the fastest 25% quartile (with mean binocular rivalry
64 Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry
rates > 0.58 Hz) in more than 50% of the 16 stimulus conditions. ‘Slow alternators’
(n = 3) recorded mean rates within the slowest 25% quartile (with mean binocular rivalry rates <0.28 Hz) in more than 50% of the 16 stimulus conditions. The resultant ‘fast’ and ‘slow’ groups were similar with respect to age (mean ages of 37 years and 42 years, respectively). The fast group comprised of three females and the slow group of one male and two females. The resulting analysis was a 2 X 2 X 2 design (luminance, movement and group).
Repeated measures ANOVA revealed there was a between-participant effect in binocular rivalry rates (F[1] = 8.201, p = .006) when stimulus strength was increased by increasing luminance and movement. However, within-participant analyses revealed an overall difference in binocular rivalry rates between the fast and slow groups when luminance was increased (F[1] = 8.092, p = .047) but not when movement was increased (F[1] = 0.774, p = .429). Paired samples t-tests revealed significant differences between binocular rivalry rates for slow alternators (n = 3) using stationary stimuli and when stimulus strength was increased from low to high luminance (t[2] = -10.961, p = .008), and high luminance stimuli with stimulus strength increasing from stationary to moving (t[2] = -13.0, p = .006). Significant differences between binocular rivalry rates were observed in stationary stimuli when stimulus strength was increased from low to high luminance (t (2) = 5.615, p =.03) in fast alternators (n = 3).
To investigate whether fast binocular rivalry alternators showed a steeper increase in binocular rivalry rate as stimulus strength increased, the difference in binocular rivalry rate recorded at low and high stimulus strength was calculated and compared in each of the four stimulus conditions; stationary, moving, low and high luminance stimuli conditions and presented graphically in Figure 2.3.
Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry 65
From Figure 2.3 it can be seen that in all conditions slow alternators (dashed lines) produced slower binocular rivalry than did fast alternators (solid lines). Their rates increased when the strength of the stimulus increased from low to high.
Comparing the difference in mean binocular rivalry rates produced by low- and high- strength stimuli in each group, the steepest increases in binocular rivalry rates occurred in faster alternators (in a manner consistent with Pettigrew, 2001) in three of the four conditions. With stationary stimuli, increasing stimulus strength by increasing the luminance increased the mean binocular rivalry rate by a difference of
0.09 Hz in slow alternators. This increase was 0.34 Hz in fast alternators. In moving
(4 c/s) stimuli, increasing stimulus strength by increasing the luminance from low to high increased the mean binocular rivalry rate by a difference of 0.09 Hz in slow alternators compared to a difference of 0.3 Hz in fast alternators. This difference was also observed with low-luminance stimuli where stimulus strength was increased from 0 c/s to 4 c/s, resulting in a 0.18 Hz increase in binocular rivalry rates in fast alternators compared with a 0.05 Hz difference in slow alternators. In high- luminance stimuli, increasing stimuli strength from 0 Hz to 4 Hz resulted in a 0.05
Hz difference in both fast and slow alternators, suggesting that at high luminance increasing the stimulus strength by movement had a similar effect in both groups.
When these results were presented graphically (Figure 2.3) and compared with the theoretical graph of Pettigrew (2001) (Figure 2.4), it is evident that slow- and fast-switchers (measured by binocular rivalry alternation rates) produced consistently slow and fast binocular rivalry rates that increased when the strength of the stimulus increased from low- to high-luminance, in a manner consistent with Pettigrew’s model (2001). The effect was seen least in individuals with a slower switch rate (for example Figure 2.4 a), who have a relatively shallow slope. Faster switchers (for
66 Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry
example Figure 2.4 d) show the steepest increase in binocular rivalry rate as a function of stimulus strength. Generally, binocular rivalry rates increased until rivalry gave way to a mixed precept; this transition varied between individuals. The highlighted rectangular area relates to the approximate variation in stimulus strength of the binocular rivalry stimuli used and depicted in Figures 2.3 and approximate rivalry rates measured.
A Low Luminance High Lumiance
1.2 1.2
1.0 1.0 1.01 0.96 z z 0.8 0.80 0.8
0.6 0.6 0.62
BR Ratein H BR Rate in H in Rate BR 0.4 0.4 0.33 * 0.24 0.2 0.2 0.28 0.19 0.0 0.0 0c/s 4c/s 0c/s 4c/s
Stationary B Moving 1.2 1.2
1.0 1.01 0.960 * 1.0 z 0.8 z 0.8 0.80 0.6 0.62 0.6
BRRate in H 0.4 BR Rate in H 0.4 0.33 0.280 * 0.2 0.2 0.24 0.19 0.0 0.0 Low Luminance High Luminance Low Luminance High Luminance
Legend Fast Slow
Statistically significant *
Figure 2.3: The effect of increasing stimulus strength on binocular rivalry rate in ‘slow’ and ‘fast’ alternators: mean binocular rivalry rates recorded by 20 healthy volunteers grouped based on the participants mean binocular rivalry alternation rate, A. The effect of increasing stimulus strength by introducing movement to low and high luminance stimuli in fast (n=3) and slow (n=3) alternators. B. Error bars show standard error.
Data in Figure 2.3 A are rearranged to highlight that binocular rivalry rates increased for both stationary and moving stimuli when stimulus strength was increased by increasing luminance contrast. Note: Error bars show standard error.
Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry 67
Figure 2.4: The effect of stimulus strength on binocular rivalry rate: Binocular rivalry rate increases as stimulus strength increases.
Note: Figure adapted from the model proposed by Pettigrew JD, Brain and Mind 2; 2001, p97.
2.7.3 Binocular rivalry dominance durations in fast and slow alternators.
Differences in the steepness of increase of binocular rivalry rates between slow and fast alternators were observed as stimulus strength increased. More frequent dominance durations (approx 150 reversals per percept) have been reported to produce a better fit to a gamma function (Brascamp et al., 2005; Brascamp et al.,
2006). It was expected that the distributions of normalised dominance durations of fast alternators would show a more-acceptable fit to the gamma-density function over the 16 stimulus conditions than slow alternators. Kolmogorov-Smirnov goodness-of- fit analyses (Conover, 1971) on the fast and slow groups revealed that the null hypothesis was unable to be rejected for any of the 16 stimuli normalised dominance duration distributions produced by the fast group, (i.e. all distributions showed an unacceptable fit to the gamma distribution). The slow group produced dominance duration distributions that demonstrated acceptable fit in six of the 16 stimulus conditions (being the low luminance of 4 c/d spatial frequency, moving and
68 Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry
stationary, chromatic and achromatic conditions; the low luminance, chromatic, 8c /d moving stimulus and the high luminance chromatic, 8 c/d stationary stimulus).
When these results were presented graphically (Figure 2.5), differences in the shape of the cumulative frequency distributions of binocular rivalry recordings of slow switchers compared with fast switchers in nine stimulus conditions can be seen.
Level of significance α is if T1 exceeds its 1 – α quantile. The test statistic, T1, is the greatest vertical distance between the two empirical distribution functions.
Normalised perceptual dominance durations in fast and slow alternators were significantly different in nine of the 16 stimulus conditions.
Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry 69
Table 2.1: The Kolmogorov-Smirnov goodness of fit analysis statistics for the dominance duration distributions for fast and slow alternators over 16 stimulus conditions (n=20). Slow Alternators Fast Alternators Stimuli KS_T p KS_T p L4AS 0.0629 *.5 0.1041 .001 L4AM 0.0575 * .5 0.0864 .001 L4CS 0.0928 * .162 0.0821 .002 L4CM 0.0746 * .25 0.0948 .001 L8AS 0.134 .029 0.0948 .001 L8AM 0.1234 .007 0.0848 .001 L8CS 0.1502 .025 0.0918 .001 L8CM 0.0728 * .25 0.0939 .001 H4AS 0.1109 .008 0.1107 .001 H4AM 0.1314 .001 0.098 .001 H4CS 0.1442 .001 0.1095 .001 H4CM 0.1418 .001 0.0974 .001 H8AS 0.1295 .001 0.1244 .001 H8AM 0.1478 .001 0.1025 .001 H8CS 0.0575 * .5 0.1003 .001 H8CM 0.1259 .001 0.06969 .001 Note: Values indicate* p >.05 acceptable fit to Gamma Distribution. Stimuli Legend: L= low luminance, H= high luminance, 4= spatial frequency of 4 c/d, 8= spatial frequency of 8 c/d, A= achromatic white/black gratings, C= coloured red/black gratings, S= stationary 0c/s and M= moving at 4 c/s.
70 Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry
Table 2.2: The two-sided Smirnov test statistic for fast and slow alternators (m and n respectively) compared with the critical values determined by of T1 at the 0.95 quantile (w0.95 ≈1.36√ m+n/ mn) across the 16 test binocular rivalry stimuli conditions (n=20).
Stimulus Slow Fast CV_T for S at Smirnov Reject
(n) (m) 95% T H0? L4AS 88 199 0.174105 0.071208 No L4AM 106 300 0.153669 0.079308 No L4CS 68 211 0.189647 0.116323 No L4CM 88 306 0.164507 0.265134 Yes L8AS 51 251 0.208891 0.296852 Yes L8AM 77 275 0.175347 0.167273 No L8CS 41 239 0.229893 1.8808 No L8CM 73 271 0.179337 0.238134 Yes H4AS 93 318 0.160326 0.216372 Yes H4AM 127 340 0.141434 0.159472 Yes H4CS 129 362 0.139453 0.284059 Yes H4CM 164 369 0.127634 0.103659 No H8AS 125 358 0.141291 0.130034 No H8AM 128 376 0.139172 0.210771 Yes H8CS 112 348 0.147747 0.735324 Yes H8CM 124 369 0.141168 0.215032 Yes
Note: *Decision to reject the null hypothesis (H0) i.e. there is no difference in the normalised dominance distribution produced by slow compared with fast alternators.
Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry 71
L4AM L4CM L8AM L8CM
1.0 1.0 1.0 1.0 0.8 0.8 0.8 0.8
y 0.6 y 0.6 y 0.6 y 0.6 0.4 0.4 0.4 0.4 Pr o bab il i t Probabilit Pr o bab il i t Probabilit
Cumulative 0.2 Cumulative 0.2 Cumulative 0.2 Cumulative 0.2 *p<0.05*ns *p<0.05 0.0 *ns 0.0 0.0 0.0 00.511.5 2 2.5 3 3.5 4 4.5 5 5.5 6 6.5 00.511.522.533.544.555.566.5 00.511.522.533.544.555.566.5 00.511.522.533.544.555.566.5 Percept Durations (sec) Percept Durations (sec) Percept Durations ( sec) Percept Durations (sec)
L4AS L4CS L8AS L8CS
1.0 1.0 1.0 1.0 0.8 0.8 0.8 0.8 y y y y 0.6 0.6 0.6 0.6 0.4 0.4 0.4 0.4 Probabilit Probabilit Probabilit 0.2 0.2 0.2 Pr o bab il i t 0.2 Cumulative Cumulative Cumulative Cumulative 0.0 *ns 0.0 *ns 0.0 *p<0.05 0.0 *ns 00.511.5 2 2.5 3 3.5 4 4.5 5 5.5 6 6.5 00.511.522.533.544.555.566.5 00.511.522.533.544.555.566.5 00.511.522.533.544.555.566.5 Percept Durations (sec) Percept Durations (sec) Percept Durations ( sec) Percept Durations (sec)
H4AM H4CM H8AM H8CM
1.0 1.0 1.0 1.0 0.8 0.8 0.8 0.8 y y y y 0.6 0.6 0.6 0.6 0.4 0.4 0.4 0.4
Probabilit 0.2 Probabilit 0.2 Probabilit 0.2 Pr o0.2 bab il i t Cumulative Cumulative Cumulative Cumulative 0.0 *p<0.05 0.0 *ns 0.0 *p<0.05 0.0 *p<0.05 00.511.5 2 2.5 3 3.5 4 4.5 5 5.5 6 6.5 00.511.5 2 2.5 3 3.5 4 4.5 5 5.5 6 6.5 00.511.522.533.544.555.566.5 00.511.522.533.544.555.566.5 Percept Durations (sec) Percept Durations (sec) Percept Durations (sec) Percept Durations (sec)
H4AS H4CS H8AS H8CS
1.0 1.0 1.0 1.0 0.8 0.8 0.8 0.8 y 0.6 y 0.6 y 0.6 y 0.6 0.4 0.4 0.4 0.4
0.2 Probabilit 0.2 Probabilit 0.2 Pr o0.2 bab il i t Pr o bab il l i t Cumulative Cumulative Cumulative Cumulative 0.0 *p<0.050.0 *p<0.050.0 *ns 0.0 *p<0.05 00.511.5 2 2.5 3 3.5 4 4.5 5 5.5 6 6.5 00.511.522.533.544.555.566.5 00.511.522.533.544.555.566.5 00.511.522.533.544.555.566.5 Percept Durations (sec) Percept Durations (sec) Percept Durations (sec) Percept Durations (sec)
Figure 2.5: Cumulative frequency distributions of normalized dominance durations recorded by fast alternators (n = 3) compared with slow alternators (n = 3) in 16 stimulus conditions.
Legend: L= low luminance, H= high luminance, 4= spatial frequency of 4cpd, 8= spatial frequency of 8cpd, A= achromatic white/black gratings, C= coloured red/black gratings, S= stationary 0c/s and M= moving at 4 c/s.
2.8 Discussion
2.8.1 Binocular rivalry rates.
In this study, the effects of increasing the stimulus strength of rival stimuli from low to high luminance, movement, colour and spatial frequency on rivalry rates rate were examined extending the work of Pettigrew and Miller (1998) and Miller et
72 Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry
al., (2003). Increasing stimulus strength of rival targets, from low to high, equally in each eye by increasing luminance and movement of the rival targets significantly increased rivalry rates in healthy volunteers. Significantly faster binocular rivalry rates were produced for stimuli of higher luminance contrast compared to those of lower luminance contrast. This is consistent with previous reports where luminance contrast was increased equally in both eyes (Alexander, 1951; Breese, 1899; Hollins,
1980; Liu et al., 1992; Mueller & Blake, 1989; Whittle, 1965) and when moving (4 c/s) were compared with stationary gratings (Blake et al., 1985). Although Blake,
Sobel and Gilroy (2003) reported longer dominance duration and slower alternation rates with moving compared to stationary rival stimuli when the stimulus was altered in only one eye. In the current study spatial frequency and colour had no effect on binocular rivalry rate. This was unexpected as long- and medium-cone pathways
(Rogers et al., 1977), as well as short-cone pathways (O’Shea & Williams, 1996), are thought to be able to generate binocular rivalry. No significant differences in binocular rivalry rates were found for high spatial frequencies (8 cpd) compared with lower spatial frequencies (4 cpd), consistent with (Blake & Fox, 1974). These results differed to Fahle (1982), Hollins (1980) Miller et al., (2003) and O’Shea et al.,
(1997), and Levelt’s alternation model (1968) with respect to spatial frequency. It should be noted that these authors did not hold luminance contrast constant, so this difference in binocular rivalry rates may reflect spatial frequency/luminance contrast interactions. The failure to find an increase in binocular rivalry rate as spatial frequency increased from 4 cpd to 8 cpd cannot be interpreted as evidence that spatial frequency does not affect binocular rivalry rate, as the range of spatial frequencies tested was limited (4 cpd versus 8 cpd was used in the current study, as these spatial frequencies were well within the binocular rivalry frequency threshold).
Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry 73
Stimuli of 1 cpd versus 10 cpd may have produced greater differences than those noted in the current study.
Regardless of whether individuals were classified as slow or fast switchers, binocular rivalry rates increased as stimulus strength increased from low to high in terms of luminance and movement. These findings were consistent with Pettigrew’s proposed oscillation model in both groups. Moreover, alternation rates in ‘faster switchers’ increased to a greater extent than in ‘slower switchers’ as stimulus strength increased from low to high - this is demonstrated by the steeper gradient of
‘faster switchers’ binocular rivalry rates in Figure 2. Although the data presented here support Pettigrew’s model in terms of the intrinsic nature of binocular rivalry rate, this study did not examine whether the perceptual alternation between conflicting images during rivalry is an inter-hemispheric phenomenon resulting from an oscillatory mechanisms that originates in brainstem (Carter et al, 2005). Other authors have suggested that reciprocal inhibition oscillators may be responsible for the binocular rivalry phenomena (Mueller & Blake, 1989). Other oscillation models of binocular rivalry have been proposed, based on neural oscillation activity occurring both in the early and late stages of the visual pathway (Laing & Chow,
2002; Lumer, Edelman & Tononi, 1997; Stollemwerk & Bode, 2003; Sohmiya,
Sohmiya & Sohmiya, 1998; Wilson, 2005).
It has been hypothesised that synchronous oscillations, involving all levels of the visual system, play a major role in the generation of rhythmic activity in binocular rivalry (Lumer et al., 1997). Oscillatory activity early in the primary visual cortex has been implicated in binocular rivalry (Lee et al., 2005; Lumer, 1998;
Polonsky et al., 2000), further along the visual pathway in the thalamus and corticothalamocortical loop (Lumer et al., 1997) and in cortical neurons (Carter et al.,
74 Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry
2005; Cosmelli et al., 2004; Srinivasan, Russell, Edelman & Tononi, 1999).
Cortical-form vision associated with binocular rivalry has been suggested to comprise multiple, hierarchically-arranged areas with feed-forward and feed-back interconnections, with neural competition a general characteristic throughout the form-vision hierarchy (Wilson, 2003). Synchronised oscillations are thought to be generated in the visual system when concentric circles and parallel lines are presented half of each form, to opposite eyes, provoking binocular rivalry (Diaz-
Caneja, 1928; O’Shea, 1999). It is thought that these oscillations enable the dichoptically viewed halves of the one form to be perceived as a whole (Alais,
O’Shea, Mesana-Alais & Wilson, 2000).
Critics of models of binocular rivalry suggest binocular rivalry originates in early stages of visual processing (V1) and have argued that early stages of visual processing produce oscillations that are too fast (in the 30 Hz range) to contribute to the rhythmic alternations of images seen in binocular rivalry. However there is ample physiological evidence indicating that slower oscillations, at speeds of 1-5 Hz
(reflecting the approximate speed of alternations in binocular rivalry) occur early in visual processing (Castelo-Branco, Neuenschwander & Singer, 1998; Cosmelli et al.,
2004; Neuenschwander, Castelo-Branco & Singer, 1999; Newman & Grace, 1999;
Rudrauf et al., 2006; Sohmiya et al., 1998; Srinivasan et al., 1999; Srinivasan et al.,
1999; Tononi et al., 1998). If this is the case, then subtle differences in the features of the rivalling stimuli are likely to increase neural firing, for example changes in target movement and luminance will result in large individual variations in binocular rivalry rate (as demonstrated here). Although these data do not enable speculation on whether the perceptual alternation of competing stimuli that occurs in binocular rivalry is related to a single switching mechanism in the visual pathway, or is the
Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry 75
result of synchronisation of oscillatory mechanisms along, or in, pathways of the visual system, the data presented here support a general oscillation model of binocular rivalry. That is, individuals have an intrinsic binocular rivalry rhythm that can be modulated with alterations to the stimulus strength.
The main findings of the current study are consistent with physiological studies that demonstrate an increase in contrast and target movement produces increased neural activity in the cortex (Freeman, 2003; Livingstone & Hubel, 1988; Logothetis
& Schall, 1989; Sengpiel, Baddeley, Freeman, Harrad & Blakemore, 1998; Sengpiel et al., 1995). An increase in binocular rivalry rate as luminance increases is thought to correlate with an increase in the ‘stimulus energy’, therefore increasing the mean firing rate of early cortical neurons (Hess, Dakin & Field, 1998). It is suggested that
V1 maps reflect the layout of neurons selective for stimulus energy, not for isolated stimulus features such as orientation, direction, and speed (Mante & Carandini,
2005). No significant increase in binocular rivalry rate was found with increasing stimulus strength in terms of spatial frequency and colour, which arguably may not contribute to ‘stimulus energy’. It is therefore possible that increased binocular rivalry rates associated with an increase in stimulus strength tracks the activity of these V1 neurons, thus presenting a behavioural measure of neural activity within the visual system.
2.8.2 Dominance durations.
The second aim of this study was to determine whether the perceptual dominance durations of faster alternators would more readily fit a gamma distribution than those produced by slower alternators (as in Brascamp et al., 2005).
The data presented here suggest the opposite. Slower alternators, those who produce fewer dominance durations, produced normalised dominance-duration distributions
76 Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry
that more frequently predicted a gamma distribution (six of a possible 16 conditions in slow alternators) compared to none in the fast alternators. Significant differences were found in the shape of the normalised perceptual dominance durations of fast and slow alternators in nine of the 16 stimulus conditions (Figure 2.5), which is cautiously interpreted as suggesting individual physiological differences that effect binocular rivalry processing.
It is unlikely that the failure to fit dominance durations to a theoretical gamma distribution function was because the binocular rivalry data from 20 individuals were pooled. Other authors demonstrated a good fit to theoretical gamma distribution functions using the method adopted here (Carter & Pettigrew, 2003; Logothetis et al.,
1996; Miller et al, 2003; Pettigrew, 1998). The unacceptable fit of the current data to the gamma distribution may have resulted from the inclusion of mixed precepts due to the two-choice method of recording the binocular rivalry perceptions. The inclusion of mixed perceptions increases the length of the dominance duration, so we would expect that in slow alternators binocular rivalry data would be less likely to approximate a gamma distribution than in fast alternators; the results presented here suggest the opposite. Furthermore, it was noted during pilot testing that recording data where mixed images were included was more difficult when using moving stimuli, producing less accurate results, than that seen with stationary stimuli.
When the distribution of normalised dominance durations were compared, using a two-sided Smirnov test, greater differences were found between slow and faster alternators at higher luminance contrast (six of the eight stimulus conditions at high luminance compared to only three in at lower luminance). The fast alternators recorded significantly shorter dominance durations (with the interval between button pushes/alternations being less than 1 second) in each condition. This suggests faster
Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry 77
visual processing at high luminance contrast in fast alternators. Thus, fast alternators are more likely to ‘see’ images of short duration and respond to them (by recording a response), so will demonstrate faster temporal resolution than slow alternators (see
Di Lollo, Hogben & Dixon, 1994; Dixon & Di Lollo, 1994; Johnson, Nozawa &
Bourassa, 1998; Kawabata, 1994; Schwartz & Winstead, 1988; Schwartz et al.,
1995).
2.8.3 Age.
Age affected the rate of binocular rivalry at low and high luminance in the study sample. This may be due to age-related visual and luminance contrast deficits that are consequential of age-induced changes in the optics of the eye and degeneration of the visual neural pathway (Jackson & Owsley, 2003; Masson et al.,
1993). Other researchers have reported similar effects (Tarita-Nistor, Gonzalez,
Markowitz & Steinbach, 2006; Ukai et al., 2003). The effects of age strengthen the view that individual physiological characteristics play a role in binocular rivalry.
Although specific conclusions cannot be drawn from the data presented here, it can be speculated that physiological factors that influence visual processing of luminance and movement, such as age related changes in dopamine and GABA activity
(Djamgoz, 1997) may play a significant role in binocular rivalry. Further investigation into these stimuli attributes, in groups with physiological variation such and in the aged or in clinical groups, may be fruitful for unlocking the mechanisms contributing to binocular rivalry and visual awareness.
2.9 Conclusion
Increasing the stimulus strength by comparing low- and high-strength stimuli in terms of luminance and movement equally in both eyes, produced significantly- increased binocular rivalry rates in 20 healthy volunteers, consistent with Levelt’s
78 Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry
fourth proposition. Individuals were grouped into slow- and fast-switchers, according to their mean binocular rivalry rate. As stimulus strength was increased from low to high, individuals with fast-switch rates showed a steeper increase in binocular rivalry rates than those with slower-alternation rates. Individuals who had slower binocular rivalry rates produced normalised perceptual dominance distributions that could be approximated to the gamma distribution more readily than those with faster alternation rates. These data support models of binocular rivalry that recognise that individual factors may influence binocular rivalry, and provide empirical data relating to Levelt’s fourth proposition.
In this study participants were classified as ‘fast switchers’ or ‘slow switchers’ according to their mean binocular rivalry rate across the sixteen stimulus conditions.
Two small comparison groups (n=3) were identified. It may have been beneficial to classify participants according to their performance on a task that provided an alternative measured visual processing speed, for example a reaction time task.
Levelt’s model suggests that participants with faster binocular rivalry rates would perform better on tasks that require faster visual processing than those with slower binocular rivalry rates. Correlations between binocular rivalry rate and comparision task may provide insights into how binocular rivalry is processed within the visual system. These investigations may inform researchers how to incorporate binocular rivalry tasks into a battery of tasks to investigate visual processing in schizophrenia and other mental illnesses in future studies.
The group of ‘fast switchers’ comprised three females with a mean age of 37 years where the group of ‘slow switchers’ comprised one male and two females with a mean age of 42 years. This introduced a potential age and gender bias. Replication
Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry 79
in a larger age and gender-matched groups is therefore necessary to confirm the results presented here.
In the next chapter, group differences in binocular rivalry are explored.
Binocular rivalry rate and dominance durations elicited from high-strength stimuli
(as reported in Pettigrew & Miller, 1998) will be compared with low-strength binocular rivalry stimuli (as reported in Miler et al., 2003) in participants with schizophrenia compared to controls, using the methods of collecting binocular rivalry.
80 Chapter 2: Altering Binocular Rivalry Rate by Increasing Luminance Contrast and Temporal Frequency: Support for an Oscillation Model of Binocular Rivalry
Chapter 3: Slower Binocular Rivalry Rates in Individuals with Schizophrenia Compared
to Healthy Controls
3.1 Binocular Rivalry Rate in Major Psychiatric Illness
Abnormal binocular rivalry has been reported in individuals with a clinical diagnosis of bipolar disorder (BPD), schizophrenia, schizoaffective disorder or depression and their relatives (Fox, 1965; Miller et al., 2003; Pettigrew & Miller,
1998; Sappenfield & Ripke, 1961; White et al., 2001; Yang et al., 2007). Slow binocular rivalry rate has been suggested as a trait marker for BPD (Pettigrew &
Miller, 1998). Miller and colleagues (2003) reliably separated participants with BPD from healthy participants using a low-strength binocular rivalry stimulus, but failed to separate healthy participants from those with either schizophrenia or depression.
However, other researchers have identified participants with schizophrenia based on their slower binocular rivalry rates (or increased mean dominance durations) (Fox,
1965; Frecska, White & Leonard et al., 2003; Sappenfield & Ripke, 1961; White et al., 2001; Wright et al., 2003), suggesting that binocular rivalry rate may not be able differentiate the type of mental illness present.
In seven out of the nine studies examining the rate of binocular rivalry and duration of dominance in rivalry in subjects with schizophrenia, the primary aim of the study was not to investigate classical binocular rivalry characteristics. Two neuroimaging studies incorporated binocular rivalry tasks in subjects with schizophrenia; one utilising functional MRI (Valle-Inclan & Gallego, 2006) and the other whole-head MEG (Tononi et al., 1998). Although these studies provide hypotheses related to defective interactions between brain regions, such as the frontoparietal network and prefrontal area and aberrations in consciousness, they provide no information about the form and frequency of binocular rivalry
Chapter 3: Slower Binocular Rivalry Rates in Individuals with Schizophrenia Compared to Healthy Controls 81
alternations in participants with schizophrenia. Most of the available data relating to binocular rivalry rate and dominance durations in schizophrenia have been produced as comparison data to address other research questions. For example, secondary hypotheses investigated binocular rivalry switch rate in BPD in the Miller et al.,
(2003) study, Yang et al., (2007) examined binocular rivalry in first-line relatives of subjects with schizophrenia and the effect of applying conflicting stimuli in rapid reversal (dichoptic stimulus alternation, DSA) were examined in two studies White et al., (2001) and Frecska, White et al., (2003). Yang et al., (2007) investigated the effect of mood states on dominance period during rivalry in subjects with schizophrenia and schizoaffective disorder. They found that increased dominance periods were related to negative mood states in those with schizophrenia, but not in healthy controls. Two early studies measured binocular rivalry in schizophrenia as their primary aim. Both found binocular rivalry rate was slower in subjects with schizophrenia compared to healthy controls (Fox, 1965; Sappenfield & Ripke, 1961).
Sappenfield and Ripke (1961) indicated that retinal rivalry in two thirty-second periods discriminated between subjects with schizophrenia and healthy participants.
Similarly, Fox (1965) noted that participants with schizophrenia recorded slower binocular rivalry rates compared to healthy participants. Their results were consistent with the view that binocular rivalry rates are inversely correlated with psychopathology; however this effect only manifested in the second two minutes of their binocular rivalry testing paradigm. No contemporary studies have primarily focussed on binocular rivalry in schizophrenia. Furthermore, the findings of
Pettigrew & Miller (1998) and Miller et al., (2003) are not well supported.
Drawing on perceptual rivalry data, and the assumption that binocular and perceptual rivalry share common mechanisms (Brascamp et al., 2006; Kanai,
82 Chapter 3: Slower Binocular Rivalry Rates in Individuals with Schizophrenia Compared to Healthy Controls
Moradi, Shimojo & Verstraten, 2005; Miller et al., 2000, Miller et al., 2003). Miller et al., (2003) argued that the perceptual rivalry findings of previous studies Eysenck
(1952), Hunt & Guilford (1933) and Philip (1953) supported their claim that slow binocular rivalry rate is a trait maker of BPD. Perceptual rivalry, or monocular rivalry, differs to binocular rivalry in that the two alternative precepts of an image are viewed by one or both eyes simultaneously, and can be seen even when one eye is closed (examples include the Necker Cube, Rubin’s Vase, and Schroder’s Staircase).
Some suggest that binocular and perceptual rivalry share several common characteristics (Kornmeier & Bach, 2004; O’Shea et al., 2009). For example, the distribution of the duration of dominance also seems to emulate a gamma distribution
(Borsellino et al., 1972; Lehky, 1995; O’Shea et al., 2009). There is high inter- participant variability in reversal rates (Borsellino et al., 1972; Kornmeier & Bach,
2004). Reversal rates can be influenced by physical properties of the stimulus (Meng
& Tong, 2004) and through voluntary control by the participants (Gomez,
Argandona, Solier, Angulo & Vazquez, 1995; Horlitz & O’Leary, 1993; Lack, 1970).
However, there are also potential mechanistic differences. For example, depth of suppression is less pronounced in perceptual rivalry (Breese, 1899; O’Shea et al.,
2009) and increases in contrast affect perceptual and binocular rivalry in opposite ways (O’Shea & Wishart, 2007). Increased contrast results in an increased alternation rate in binocular rivalry, and a decreased alternation rate in perceptual rivalry (O’Shea et al., 2009). Attention may influence Necker Cube reversals more than binocular rivalry alternations (Meng & Tong, 2004; Tong, 2001; Van Ee et al.,
2006).
As previously noted, in terms of schizophrenia, the available perceptual rivalry data are not conclusive. The data of Levander et al., (1985) suggest slower reversals
Chapter 3: Slower Binocular Rivalry Rates in Individuals with Schizophrenia Compared to Healthy Controls 83
in participants with schizophrenia, whereas a much earlier study (Hunt & Guilford,
1933) reported that participants with ‘dementia praecox’ (an older term for schizophrenia) had normal Necker reversal rates. Participants with schizophrenia perceived the Schroder’s Staircases from above for significantly less time then the perception of the stimulus from below, and had a tendency to have more reversals than controls; however this was not significant (Calvert, et al., 1988). Similarly,
Hoffman et al., (2011) and Keil et al., (1998) reported that participants with schizophrenia had faster reversals than healthy controls for the Rubin’s Vase. Thus, it is difficult to argue that perceptual rivalry data support binocular rivalry data in schizophrenia.
There is also discussion in the literature as to whether binocular rivalry and perceptual rivalry reflect distinct (or similar) neural mechanisms based on whether or not the percept durations have similarly-shaped distributions (Van Ee et al., 2006).
Dominance durations vary, are stochastic (random) (Blake, Fox & McIntyre, 1971), statistically independent of each other (Fox & Herrmann, 1967; Walker, 1975) and typically form gamma distributions when plotted as histograms (Brascamp et al.,
2005; Brascamp et al., 2006; Fox & Herrmann, 1967; Levelt, 1967; Logothetis et al.,
1996). However, there is debate as to whether gamma-shaped distributions of dominance durations are a true characteristic of binocular rivalry. Dominance durations reported in the current study fitted gamma distributions on six of 16 occasions. Other researchers have also failed to fit normalised dominance durations derived from healthy participants to gamma distributions (Brascamp et al., 2005;
Brascamp 2006; Murata et al., 2003). Zhou et al., (2004) found that during monocular rivalry, perceptual dominance distributions in participants with
84 Chapter 3: Slower Binocular Rivalry Rates in Individuals with Schizophrenia Compared to Healthy Controls
schizophrenia fitted log-normal, Weibull and gamma distributions. This suggests that multiple or different neural pathways may be involved.
In terms of dominance durations, Miller et al., (2003) found that normalised dominance durations of binocular rivalry in healthy participants or those with depression, BPD or schizophrenia were able to be ‘fitted’ to gamma distributions.
However, these authors provided no information regarding perceptual rivalry. The data from Miller et al., (2003) and the existing available literature paint an unclear picture with respect to whether participants with schizophrenia have binocular rivalry rates and dominance distributions that differ from those of healthy participants. In order to support Pettigrew and Miller’s assertion that slow binocular rivalry rate is a trait marker for BPD, it is important to examine binocular rivalry rate in other mental disorders, such as schizophrenia, to examine the generalisability of this characteristic.
3.2 Study 2
3.2.1 Aims.
Two classic studies, Fox (1965) and Sappenfield & Ripke (1961) report slower binocular rivalry rates in schizophrenia, that contrast with the study of Miller et al.,
(2003) which found no difference. In order to address this conflict, the aim of the current study was to advance the work of Miller et al (2003), to ascertain whether there are differences in binocular rivalry rate and dominance durations in individuals with schizophrenia compared to healthy controls using their methods. It was predicted there would be no difference in binocular rivalry rates recorded by participants with schizophrenia compared to healthy controls using low-strength binocular rivalry stimuli (as in Miller et al., 2003), but would be faster or the same when using high-strength binocular rivalry stimuli (as in Pettigrew & Miller, 1998
Chapter 3: Slower Binocular Rivalry Rates in Individuals with Schizophrenia Compared to Healthy Controls 85
with BPD). Faster or similar binocular rivalry rates in participants with schizophrenia would support the claim that slower binocular rivalry rates are a trait marker for BPD. Conversely, slower binocular rivalry rates in participants with schizophrenia would question whether slow binocular rivalry is a trait marker for
BPD, and the utility of this task as a potential diagnostic tool. Alternation rates and dominance durations in binocular rivalry and in a perceptual rivalry task (Necker
Cube) were also compared in subjects with schizophrenia using a within-participant design.
3.2.2 Hypotheses.
The main hypothesis of the current study was that binocular rivalry rates recorded by participants with schizophrenia and a perceptual rivalry task (the Necker
Cube) would be slower than those recorded by controls. It was also hypothesised that normalised dominance durations would approximate a gamma distribution.
3.3 Method
Binocular rivalry rate and dominance durations were recorded for two binocular rivalry tasks (one low-strength stimulus and one high-strength stimulus) and one perceptual rivalry task in participants with schizophrenia (n = 20) and healthy controls (n = 20). The same binocular rivalry methods and stimulus conditions as described in Chapter 2, Section 2.2.2.1, were used.
3.3.1 Participants.
Written and informed consent were obtained from each participant before commencement of binocular rivalry testing. Ethical clearance for this study was obtained from the Royal Brisbane and Women’s Hospital Human Research Ethics
Committee and the Queensland University of Technology Human Research Ethics
Committee. Binocular rivalry testing took place at an outpatient facility of the Royal
86 Chapter 3: Slower Binocular Rivalry Rates in Individuals with Schizophrenia Compared to Healthy Controls
Brisbane and Women’s Hospital and in the Optometry Clinic at the Queensland
University of Technology.
All participants were right-handed, as assessed using the Annett Handed
Questionnaire (Annett, 1970). All participants had normal vision and at least 6/9 visual acuity (corrected if necessary) in each eye assessed by the Snellen visual acuity testing. To reduce any eye dominance effect related to inter-ocular differences in visual acuity, participants were excluded from the study if visual acuity in each eye was not equal (to within two letters). In addition, each participant undertook a keyhole task to determine sighting eye dominance as described in (Osburn &
Klingsporn, 1998). The dominant sighting eye identified by the hole-in-card test reliably coincides with the dominant eye as determined by binocular rivalry, which is a useful quantitative indicator of eye dominance in clinical applications (Handa, et al., 2004). As an indication of predicted IQ all participants completed the National
Adult Reading Test (NART) (O’Carroll et al., 1992; Crawford et al., 1992; Morrsion,
Sharkey, Allardyce Kelly & McCreadie, 2000). All participants were instructed to abstain from caffeinated drinks for four hours and nicotine for one hour prior to binocular rivalry testing, as caffeine and nicotine may increase binocular rivalry rate
(George, 1936).
3.3.1.1 Healthy participants.
Twenty control participants, with no previous history of neurological disease or mental illness (confirmed using the Structured Clinical Interview for the
Structured Clinical Interview for the DSM-IV [SCID]), were recruited to the study.
3.3.1.2 Participants with schizophrenia.
Twenty participants with a clinical diagnosis of schizophrenia were recruited.
Clinical diagnosis of schizophrenia was confirmed using the DSM-IV (SCID). The
Chapter 3: Slower Binocular Rivalry Rates in Individuals with Schizophrenia Compared to Healthy Controls 87
researcher (a Registered Mental Health Nurse) had previously undertaken training in the use of the DSM-IV (SCID). Competence confirmed by inter-rater reliability testing with two consultant psychiatrists. Nine participants met the schizophrenia sub-type classification of paranoid schizophrenia with the remaining 11 categorised to the undifferentiated schizophrenia sub-type. One participant was unable to complete the NART due to inadequate literacy skills. The participant characteristics of both groups are described in Table 3.1.
Table 3.1: Age, gender, eye dominance and NART scores of controls and participants with schizophrenia
Controls Schizophrenia χ2 df p (n=20) (n=20) Age Mean (yrs) 37.8 37.9 Range 21-64 264 25.667 25 0.426 Gender Male 4 15 Female 16 5 12.13 1 0.001 Eye Dominance R)eye 11 12 L)eye 9 8 0.417 1 0.519 NART Score Mean 116 109 Range 102-122 105-125 22.687 18 0.196
All participants with schizophrenia were taking an anti-psychotic medication at the time of testing; drugs and doses were converted to chlorpromazine equivalents
CPZE (Centorrino et al., 2002; Hargreaves, Zachary, LeGoullon, Binder & Reus,
1987; Humberstone, Wheeler & Lambert, 2004; Owen et al., 2002; Woods, 2003) and ranged from 200-900 mg/day with the mean dose being 482.5 mg/day, and a median dose of 425 mg/day. Symptoms of schizophrenia were rated according to the
Positive and Negative Syndrome Scale (PANSS) (Kay, Opler & Lindenmayer,
1988). Participants were grouped into having either positive or negative symptoms,
88 Chapter 3: Slower Binocular Rivalry Rates in Individuals with Schizophrenia Compared to Healthy Controls
based on a composite scale derived from subtracting negative symptom rating scores from positive scores on the PANSS (see Kay et al., 1988). Participants were classified as experiencing a predominance of positive symptoms if their resulting score was >0 (n = 9), or a predominance of negative symptoms if their score was <0
(n = 9). Two participants had a score of 0, indicative of equal positive and negative symptoms. The two groups were well matched for age but not gender.
3.3.1.3 Procedure
3.3.1.3.1 Binocular rivalry testing.
To ensure that reliable data were collected, all participants received training in the binocular rivalry task before testing. Binocular rivalry stimuli were presented on a personal computer placed three metres from the participant. The participant viewed the stimulus through liquid crystal shutter goggles that presented vertical or horizontal gratings exclusively to each eye. Participants recorded their percepts on a computer key pad attached to a second personal computer that collected binocular rivalry data. The apparatus and method of collecting binocular rivalry used here were identical to those employed in the study by Miller et al., (2003).
Each participant was tested using two binocular rivalry stimulus conditions; a low- and high-strength stimulus. The low-strength stimulus consisted of a circular field (1.5 degrees diameter) filled with monochromatic, stationary, 4 cpd, square wave gratings of 90% luminance contrast. The high-strength stimulus consisted of the same circular field filled with monochromatic, 8 cpd, square wave gratings of
100% luminance contrast, moving at approximately 4 cps. The velocity of the moving lines was determined by separately counting the number of vertical and horizontal lines that moved beyond the edge of the circular grid in a one minute time period; this was then converted to cycles per second. The stimulus characteristics of
Chapter 3: Slower Binocular Rivalry Rates in Individuals with Schizophrenia Compared to Healthy Controls 89
these two targets were chosen to match the low- and high-strength stimuli used in
Pettigrew and Miller, (1998) and Miller et al., (2003).
Luminance levels were measured at a distance of three metres through the shutter goggles (NuVisionTM60GX , MacNaughton, Canada) using a luminance colourimeter (model BM-7, Topcon, Japan). The maximum luminance condition was determined by the maximum luminance capability of the computer monitor, with luminance levels measured through the goggles averaging 60% less than those without the goggles. The luminance contrast of each stimulus was calculated using
Michelson’s formula, (Lmax - Lmin) / (Lmax + Lmin) (Slaghuis, 1998). Luminance contrast was calculated as 1.0 in the high-strength stimulus condition and 0.9 in the low-strength condition.
Initially participants were asked to record when they perceived horizontal lines, vertical lines and mixed images (as reported in Miller et al., 2003). However, during pilot experiments it became obvious that the percept changing from vertical to horizontal was difficult to determine for the high-strength task; there was high measurement variability when data were collected in this manner. To improve the accuracy of the data collected, participants were required to report only two conditions, that is when vertical lines were exclusively seen and when horizontal lines were exclusively seen. Participants were told to ignore mixed or combined images. Participants only commenced the formal binocular rivalry testing when the researcher was satisfied they understood the instructions by verbally reporting their perceptions and accurately recording the alternation between vertical and horizontal perceptions on a computer key pad (i.e. their verbal reports matched keyboard responses).
3.3.1.3.2 Perceptual rivalry testing; the Necker cube.
90 Chapter 3: Slower Binocular Rivalry Rates in Individuals with Schizophrenia Compared to Healthy Controls
For the perceptual rivalry task, a black line drawing of the Necker Cube measuring 7.5cm, extending 1.5 degrees of visual angle, was presented on a personal computer at a distance of three metres. Each participant was instructed to view the
Necker Cube passively and to verbally indicate when they perceived the cube viewed, as seen from above, and when it changed and appeared to be seen from below. When participants could confidently verbally signal the alternation between views they were asked to indicate when the cube appeared to be viewed from the front using the left response key, and when viewed from the back using the right response key of the computer key pad (Kornmeier & Bach, 2004).
3.4 Statistical Analyses
A power analysis was performed to determine the minimum number of participants that were required to demonstrate a difference in binocular rivalry rates in low-strength stimuli (as used in Miller et al., 2003) and high-strength stimuli (as used in Pettigrew and Miller (1998). The data provided by Miller et al., (2003) were entered into the G*power3 program (Faul, Erdfelder, Lang & Buchner, 2007). It was estimated that a sample size of 20 in each group was required for a two-sided 5% significance level and power of 80 to demonstrate a difference in binocular rivalry rate in the low- and high-strength binocular rivalry tasks in the participants with schizophrenia compared to the healthy controls.
As the resulting binocular rivalry rates did not form normal distributions, non- parametric statistics were used. Kruksal-Wallis one-way non-parametric ANOVAs were performed to determine the effects that group, gender, age, education and
NART score had on binocular rivalry rate. To examine influences on binocular rivalry rate in participants with schizophrenia, the analyses focussed on three factors unique to the participants with schizophrenia: diagnostic sub-group (by DSM-IV
Chapter 3: Slower Binocular Rivalry Rates in Individuals with Schizophrenia Compared to Healthy Controls 91
classification), type of schizophrenia symptoms (positive versus negative, as determined by PANSS), and the dose of anti-psychotic medication quantified as chlorpromazine equivalents (CPZE) were made (Mann-Whitney U tests). Data are mean ± SD, unless otherwise stated.
The time intervals between responses that signal the onset of perceptual alternations (measured in seconds) were normalised by dividing each interval by the mean. Dominance duration intervals were normalised and cumulative gamma distributions plotted. Classically, normalised dominance durations have been plotted as histograms and fitted to a gamma distribution using a Kolmogorov-Smirnov goodness-of-fit test (Borsellino et al., 1972; Carter & Pettigrew, 2003; De Marco et al., 1997; Levelt, 1968; Logothetis et al., 1996; Miller et al., 2003; Pettigrew &
Miller, 1998; Van Ee et al., 2006). However, normalised binocular rivalry dominance durations do not always form gamma distributions in healthy participants
(Brascamp et al., 2005; Brascamp et al., 2006; Cogan, 1973, De Marco et al., 1977;
Zhou et al., 2004), or those with schizophrenia (Miller et al., 2003). Thus, differences in the resulting distributions of normalised dominance intervals were compared, rather than attempting to fit dominance intervals to gamma distributions.
To determine whether there were any differences in the distributions of dominance intervals produced by participants with schizophrenia compared to healthy controls, a two-sided Smirnov test was conducted for each condition, as described in Section
2.5.3.1. In each binocular rivalry condition the data consisted of two independent random samples, one of size n, X1, X2 …. Xn (dominance durations recorded by participants with schizophrenia) and the other of size m, Y1, Y2, …. Ym (dominance durations recorded by healthy controls). The decision rule, to reject H0 at the level significance α is if T1 exceeds its 1 – α quantile; where n (the number of dominance
92 Chapter 3: Slower Binocular Rivalry Rates in Individuals with Schizophrenia Compared to Healthy Controls
durations for the smallest sample- schizophrenia participants) and m (the number of dominance durations for the largest sample- healthy controls) is greater than 20, the
0.95 quantile of T1 is given by w0.95 ≈1.36√ m+n/ mn (Conover, 1971).
In essence, the Smirnov test is a statistical test that determines the degree of difference in the normalised distributions of data, regardless of the shape of the distribution. The Smirnov test compares the differences of the values along the distribution at specific points (bins). If there is more than a 0.05 difference in values at any point along the two distributions (as indicated by the vertical distance between two values) the criteria for a statistical difference in the dominance durations is met
(Conover, 1971).
3.5 Results
3.5.1 Binocular rivalry rate.
Binocular rivalry rate was significantly slower in participants with schizophrenia compared the control group for both the high- and low-strength stimulus conditions (Figure 3.1). Participant group had a significant main effect on binocular rivalry rate for both stimulus conditions; low-strength condition χ2 =
12.952, df =1, p < .001 and high-strength condition χ2 = 12.662, df =1, p < .001. In the low-strength stimulus condition binocular rivalry rates in the participants with schizophrenia averaged M= 0.28 Hz, SD = 0.108 Hz, which was nearly half the speed of that for controls participants where binocular rivalry rates averaged M= 0.545, SD
= 0.256Hz. Binocular rivalry rates in the group comprising of participants with schizophrenia were significantly slower (Z = -3.612, p < .001). Binocular rivalry rates in the high-strength stimulus condition were also significantly slower (Z = -
3.545, p < .001) in this group (M = 0.298, SD = 0.126 Hz) compared to controls (M
= 0.548, SD = 0.256Hz).
Chapter 3: Slower Binocular Rivalry Rates in Individuals with Schizophrenia Compared to Healthy Controls 93
Age (χ2 [21, 40] =.124, p = .725), gender (χ2 [1, 40] = .165, p = .685), eye dominance (χ2 [5, 40]= 1.000, p = .317) and NART score (χ2 [14, 40] = 1.091, p =
.296) (Kruksal-Wallis) had no effect on binocular rivalry rate for either stimulus condition i.e. none of the tested within-participant variables appeared to affect binocular rivalry rate and none acted as measurement confounders.
3.5.2 Necker Cube alternation rates.
In contrast, the rate of perceptual alternations did not differ (Z = -0.406, p =
6.698) in the group with schizophrenia (M = 0.327, SD = 0.236 Hz) compared to controls (M = 0.343, SD = 0.185 Hz) for the Necker Cube task (Figure 1). Age, gender, education and NART score had no effect on the rate of perceptual alternations in either group (Kruksal-Wallis χ2, p > 0.05). Alternation rates for the
Necker Cube in control participants were slower than for the binocular rivalry tasks.
Binocular rivalry rates compared with Necker Cube perceptual alternations in healthy controls in the low-strength condition Z = -3.509, p < .001, and in the high- strength condition Z = -3.733, p < .001 (Wilcoxon sign ranks test). Participants with schizophrenia recorded similar Necker Cube perceptual alternation rates as binocular rivalry rates; in the low-strength condition Z = -0.485, p =.627, and in the high- strength condition Z = -0.423, p < .673 (Wilcoxon sign ranks test). These data are presented in Figure 3.1.
94 Chapter 3: Slower Binocular Rivalry Rates in Individuals with Schizophrenia Compared to Healthy Controls
0.7
0.6 0.545 0.548 0.5
0.4 0.343 0.326 0.3 0.283 0.298 second) 0.2
0.1
0 BR Low Srength BR High Strength Necker Cube
Alternation Rate in Hz (Button pushes per per pushes (Button Hz in Rate Alternation Condition Condition
Schizophrenia Control
Figure 3.1: Mean alternation rates recorded in schizophrenia participants (n = 20, grey diamonds) compared to healthy controls (n = 20, black squares) in two binocular rivalry tasks.
Note; Error bars indicate standard error.
Based on the SCID DSM-IV results, participants with schizophrenia formed two distinct diagnostic sub-groups groups; those with paranoid schizophrenia (n = 9) and undifferentiated schizophrenia (n = 11). Statistical testing revealed that diagnostic sub-group did not affect binocular rivalry rate for either stimulus condition (low Z = -0.228, p =.82 and high Z = 0.209, p = .23). Similarly, whether participants with schizophrenia reported positive or negative symptoms scores had no effect on binocular rivalry for either stimulus condition (low-strength Z = -.44, p
=.965 and high-strength Z = -0.973, p = .331). All participants tested were taking anti-psychotic medication for the treatment of their symptoms (four were taking
Olanzapine, four Risperidone, six Clozapine, one Quetiapine, one Aripiprazole, one
Amisulphride, and three were taking typical antipsychotic medications, one
Fluphenazine, one Haloperidol and one Zuclopenthixol). As previously noted, chlorpromazine equivalents (CPZE) were calculated for each medication, so that the
Chapter 3: Slower Binocular Rivalry Rates in Individuals with Schizophrenia Compared to Healthy Controls 95
effects of medication could be compared across participants, see Woods, (2003) and
Centorrino et al., (2002). Medication dose was compared using a median split;
CPZEs of lower than 425 mg were considered a lower dose, and higher doses were considered as those greater than 425 mg. Statistical testing revealed no effect of medication on binocular rivalry rates measured using the low-strength stimulus (Z =
0.63, p = .103), however for the high-strength stimulus condition a medication effect was found (Z = -2.271, p = .023). Participants taking lower doses (lower than the median) of anti-psychotic medications recorded faster binocular rivalry rates (mean
0.311 Hz compared 0.278 Hz).
3.5.3 Normalised mean dominance durations.
For all three rivalry tasks (both binocular rivalry tasks and the Necker Cube task), the normalised mean dominance durations recorded by both groups failed to form gamma distributions (Kolmogorov-Smirnov p >.05). Whether participants with schizophrenia and healthy controls produced different distributions of dominance durations were examined (see Section 3.5). No differences in the normalised dominance distribution were produced by participants with schizophrenia compared to healthy controls. Table 3.2 shows the Smirnov test statistic for participants with schizophrenia and healthy control participants (m and n, respectively) compared with the critical values determined by w0.95 ≈1.36√ m+n/ mn (CV-T for S) compared to the Smirnov T (the greatest distance in values along the distribution) across the three test conditions.
96 Chapter 3: Slower Binocular Rivalry Rates in Individuals with Schizophrenia Compared to Healthy Controls
Table 3.2: Smirnov test statistic for participants with schizophrenia (n=20) and controls (n=20).
Test stimulus Schizophrenia Healthy CV_T for S at 95% Smirnov T Reject (n) (m) H0? Low Strength 4992 10488 0.06614 0.062034 No
High Strength 5024 9920 0.06661 0.056328 No
Necker Cube 6672 6904 0.06603 0.019091 No
Viewing the plotted cumulative normalised dominance durations in Figure 3.2, that compare the two distributions, there were no discernible differences. On examination of the cumulative probability functions, there were no significant differences in the vertical distances between the two plots at any point in Figure 3.2, indicating that the mean dominance durations recorded by participants with schizophrenia were not significantly different to that of the healthy controls. These results indicated that it was only rate of binocular rivalry alternations that differed between participants with schizophrenia and healthy controls, and not the duration or proportion of time spent viewing (or suppressing) each image before being interrupted by the alternative image.
3.6 Discussion
Binocular rivalry rates in participants with schizophrenia were slower than healthy controls in both the low-strength and high-strength binocular rivalry tasks.
However, no differences in the perceptual alternation rates of the Necker Cube
(monocular rivalry) task were found between the two groups. Perceptual alternation rates for the Necker Cube task in schizophrenia were similar to the alternation rates recorded in the two binocular rivalry tasks, however Necker Cube alternation rates were slower in healthy controls compared to binocular rivalry rates. There were no
Chapter 3: Slower Binocular Rivalry Rates in Individuals with Schizophrenia Compared to Healthy Controls 97
group differences in the distribution of normalised dominance durations in the two binocular rivalry tasks and the monocular rivalry task. See Figure 3.2.
Low Strength Condition
1.0 0.8 0.6 0.4 Probability Cumulative Cumulative 0.2 0.0 0123456789101112 Dominance Durations in Seconds
Control Schizophrenia
High Strength Condition
1.0 0.8 0.6 0.4 Probability Cumulative Cumulative 0.2 0.0 0123456789101112 Dominance Durations in Seconds
Control Schizophrenia
Necker Cube
1.0 0.8 0.6 0.4 Probability Cumulative 0.2 0.0 0123456789101112 Dominance Durations in Seconds
Control Schizophrenia
Figure 3.2: Normalised mean dominance durations (the time intervals between button pushes (in seconds)/mean) plotted as cumulative distributions.
It is possible that the difference in rates between the two samples was due to medication. In the current study all participants were taking a single dose of anti- psychotic medication (dose range 200-900mg in CPZE). Anti-psychotic dose was not stated in Miller et al., (2003), so no dose comparisons could be made. In the
98 Chapter 3: Slower Binocular Rivalry Rates in Individuals with Schizophrenia Compared to Healthy Controls
Miller et al., (2003) study the four participants were taking two different types of medication. Three subjects were taking both a typical and an atypical anti-psychotic, and one was taking lithium. Lithium is typically prescribed for mood disturbances.
It is not clear from Miller et al., (2003) whether co-morbidity was an exclusion criterion as it was in the current study. Another possible reason for the difference in results is that only 12 of the 18 participants with schizophrenia in the Miller et al.,
(2003) study had normal vision. All participants in the current study had normal vision (or normal corrected vision).
It is unlikely that these findings are due to group differences between the studies. Participants with schizophrenia in the current study were similar in age to those in Miller et al., (2003); mean age 37.9 years (range 23 -64 years) and 37.7 years (range 21-69 years) respectively. Although in Miller et al., (2003) the group with schizophrenia comprised nine males and nine females compared to 15 males and five females, in the current study, this difference was not significant (χ2 = 2.544, p = .11). Age and gender had no effect on binocular rivalry rate for either stimulus condition or acted as measurement confounders for either group in the current study.
3.6.1 Binocular rivalry rates in schizophrenia.
Binocular rivalry rates in participants with schizophrenia were consistently slower than those in healthy participants for both low- and high-strength stimulus conditions. The data presented here are consistent with the work of Fox (1965) and
Sappenfield and Ripke (1961) who found binocular rivalry rate to be slower in participants with schizophrenia compared to healthy controls. Furthermore, they contrast with the findings of Miller et al., (2003) where no differences were found.
Miller and colleagues dismissed the work of Sappenfield and Ripke (1961) and Fox
(1965) on the basis that these studies were limited by the short observation period
Chapter 3: Slower Binocular Rivalry Rates in Individuals with Schizophrenia Compared to Healthy Controls 99
where binocular rivalry data were collected for less than two minutes for each participant. The data presented here replicate slow binocular rivalry rate in a group of 20 participants with schizophrenia over eight minutes of binocular rivalry data collection. In addition, this was across two different binocular rivalry stimulus conditions.
3.6.2 Monocular rivalry rates in schizophrenia.
No differences were found when rivalry rates and dominance durations of the two perspectives of the Necker Cube were compared between the two groups. These results suggest that perceptual rivalry may be a product of different mechanisms than binocular rivalry. Meng and Tong (2004), Tong (2001) and Van Ee et al., (2006) propose a higher cortical based mechanism of binocular rivalry. However, in terms of rate, healthy control participants recorded slower Necker Cube rates than binocular rivalry rates. This effect in healthy participants has been found previously by Breese who reported that monocular rivalry alternations tended to occur at a slower rate than binocular rivalry alternations and tended to be less vivid (Breese,
1899). Slower Necker Cube alternations or monocular rates were not observed in participants with schizophrenia. It could be that the slow binocular rivalry rate observed in the group with schizophrenia limits the ability to detect further slowing in the monocular task. A more likely explanation is that the features of schizophrenia that effects higher cortical processing (for example attention, visual and verbal learning and memory, working memory and executive functioning), also effect processing in the visual cortex. Recent models suggest that monocular rivalry
(or alternation between alternative images in ambiguous figures) involves competition for visual awareness between the monocular neurons higher in the visual cortex (V2 and beyond), whereas binocular rivalry involves both bottom-up and top-
100Chapter 3: Slower Binocular Rivalry Rates in Individuals with Schizophrenia Compared to Healthy Controls
down processing (Struber, 1999) that includes processing as early as V1 (Tong &
Engel, 2001). That is, inter-ocular competition between binocular neurons earlier in visual processing are influenced by local stimulus characteristics (contrast, temporal frequency) that drive binocular and monocular neurons higher in cortical visual processing (V1 and beyond) are responsible for bringing the opposing images into consciousness (Kornmeier & Bach, 2005; O’Shea et al., 2009; Tong, 2001).
Therefore, abnormal monocular neurons in the higher visual cortex may affect the rate in which opposing images are brought into conscious in both binocular and monocular rivalry in schizophrenia).
3.6.3 Distributions, gamma plots.
The distributions of dominance durations between the two groups were directly compared using the Smirnov test. No statistical differences were found in the distributions of dominance duration between participants with schizophrenia or healthy controls for either the binocular rivalry task or the perceptual rivalry task.
Thus the characteristics of binocular rivalry in terms of dominance durations were similar, with the two groups only showing differences in binocular rivalry rates.
These data are at odds with the findings of Miller et al., (2003). These authors reported normalised dominance durations produced by healthy participants, those with BPD and those with depression fitted a gamma distribution (with R2 values of greater than 0.96), while those produced by participants with schizophrenia fitted less well (R2 = 0.92). These differences between the two studies in reported dominance durations in schizophrenia may be due to the statistical methods employed. Miller et al., (2003) fitted dominance durations of the respective groups to Gamma distributions using the Kolmogorov-Smirnov test. This was not attempted here as it was reported in Chapter 2 that dominance durations reported by the sample of control
Chapter 3: Slower Binocular Rivalry Rates in Individuals with Schizophrenia Compared to Healthy Controls101
participants in this study did not generally fit Gamma distributions (see Section
2.7.1). Here the ‘Two Sample Smirnov Test’ was used to compare distributions of dominance durations reported by controls and participants with schizophrenia.
Although there was no difference in the cumulative dominance distributions, allowing one to assume that both groups recorded binocular rivalry dominance distributions that were ‘normal’ and ‘expected’, it is impossible to distinguish whether either group’s distributions fitted a Gamma distribution. Although unlikely, based on the study reported in Chapter 2, it possible that both controls and participants with schizophrenia recorded binocular rivalry dominance durations that fitted a Gamma distribution, or they both deviated from the Gamma distribution to the same degree.
3.6.4 Effect of stimulus strength.
It was expected that a significant increase in binocular rivalry rate would be seen in both groups as stimulus strength increased, as it has been repeatedly reported that increasing the strength of the binocular rivalry stimulus increases binocular rivalry rate in healthy controls (Breese, 1899; Fahle, 1982; Levelt, 1968; O’Shea,
1997; O’Shea & Williams, 1996; Rogers et al., 1977). The stimulus strength for high- and low-stimulus used here were the same as those reported by Miller et al.,
(2003) and Pettigrew and Miller, (1998). However, binocular rivalry rates were unchanged by alterations to stimulus strength in both participant groups. This contrasts with the results for healthy control participants in Miller et al., (2003), who reported binocular rivalry rates of 0.42 Hz (n = 30) in a lower-strength stimulus, and in Pettigrew and Miller (1998), who reported rates of 0.60 Hz (n = 63) with the higher strength stimulus. Binocular rivalry rates here are approximately 0.54 Hz for both stimulus strengths.
102Chapter 3: Slower Binocular Rivalry Rates in Individuals with Schizophrenia Compared to Healthy Controls
While moving rivalrous stimuli presented at equal strength to each eye, lead to a greater suppression, and therefore faster binocular rivalry rates, than static patterns
(Norman, Norman & Bilotta, 2000; Cobo-Lewis, Gilfory & Smallwood, 2000), it is unlikely that a change in spatial frequency from 4 cpd to 8 cpd or a 10% difference in luminance contrast (0.9 compared to 1.0) would contribute to an increase in binocular rivalry rate. Thus, it is not surprising that there was no difference in binocular rivalry rate observed with stimulus strength. This is most likely due to the inclusion of movement and a modest increase in luminance contrast in the higher- strength task. Previous data (Liu et al., 1992) suggest that stimulus luminance contrast would need to be reduced to below 0.5 for a change in binocular rivalry rate of the magnitude observed by Miller et al., (2003) and Pettigrew and Miller (1998), when measured in the same participants.
3.6.5 Diagnostic value of binocular rivalry rate.
Prior research has proposed that binocular rivalry rate is able distinguish those with schizophrenia from non-psychotic illness. The current data, taken together with previous findings, suggest binocular rivalry rate may distinguish those with major psychiatric illness from healthy individuals. The classic ‘Kraepelin differentiation of schizophrenia and bipolar disorder’ is questionable (see Greene (2007) for a review).
It is possible that differences in binocular rivalry rate reflect general cognitive deficits or abnormal neurotransmitter function within the central nervous system. As previously noted, neurotransmitter involvement in binocular rivalry has been demonstrated using the traditional hallucinogenic beverage ‘Ayahuasca’ (Carter et al., 2005; Frecska, White & Luna, 2003; Frecska, White et al., 2003). The active ingredient is Psilocybin, a (serotonin) 5HT1A and 5HT2A agonist, decreases binocular rivalry rate in a dose-dependent manner (Carter et al., 2005; Carter et al.,
Chapter 3: Slower Binocular Rivalry Rates in Individuals with Schizophrenia Compared to Healthy Controls103
2007; Nagamine et al., 2007). Similar results have been reported using
Tandospurone, a 5HT1A agonist (Nagamine et al., 2008).
3.6.6 Physiological mechanisms for the slowing of binocular rivalry rate.
While the exploration of serotonin agonists’ effects on binocular rivalry rate is logical based on Pettigrew and Miller’s suggestion that slow binocular rivalry rate is a trait maker for BPD, this is not direct evidence to support this suggestion.
Although serotonin is related to the pathogenesis of BPD other neurotransmitters also play a role, for example the glutamatergic and cholinergic systems (muscarinic and nicotinic systems) and melatonin (Zarate, 2008). Pettigrew and colleagues suggest the slow binocular rivalry rate is due to the effect of serotonin on oscillatory mechanisms within the brainstem, where there is a high concentration of serotonin receptors. However, serotonin receptors are widely throughout the human brain including the mesolimbic regions. In these regions agonism of serotonin (particularly
5HT2A) receptors is likely to stimulate dopamine release. Psilocybin ingestion has been shown, using positron emission tomography (PET) to enhance striatal dopamine release in healthy volunteers (Vollenweider et al., 1999). Modifications in qEEG with ingestion of Tandospurone are reported to be in line with other pro- serotoninergic and pro-dopaminergic drugs (Riba, Rodriguez-Fornells & Barbanjo,
2002). These effects on binocular rivalry rate can as easily be accounted for in the serotonin-mediated release of dopamine in the striatum. Furthermore, stimulation of
5HT2A receptors has also been implicated in dopamine release through the action of
GABA pathways (Vollenweider et al., 1999). Dopamine has also been implicated in
BPD (Pearson et al., 1995; Yatham et al., 2005) and post-traumatic stress disorder
(PTSD), depression and anxiety (Barnes et al., 2006; Freeman, Freeman & McElroy,
2002; Seeman et al., 2002). Neurotransmitters have complex interactions within the
104Chapter 3: Slower Binocular Rivalry Rates in Individuals with Schizophrenia Compared to Healthy Controls
central nervous system; it is likely that most mental illnesses will involve common neurotransmitter activity, which is reflected in the overlapping of symptoms and treatment modalities.
3.6.7 Effect of schizophrenia medication dose.
Slow binocular rivalry rates were found in participants with schizophrenia, a disorder hypothesised to be caused by abnormally high levels of dopamine in the central nervous system, with major treatments consisting of agents that block dopamine (Abi-Dragham, 2004; Fudge & Emiliano, 2003; Kapur & Mamo, 2003).
In the current study significant differences were seen in binocular rivalry rate by dose of anti-psychotic agents, with slower binocular rivalry rates seen at higher doses.
Furthermore, severity of symptoms of schizophrenia (measured by PANSS scores) was associated with increased anti-psychotic dose (in CPZE) (Z = -3.93, p < .001), suggesting that participants with schizophrenia experiencing more symptoms of their illness recorded slower binocular rivalry. These factors suggest a role of dopamine activity in binocular rivalry. Dopamine involvement in binocular rivalry seems likely as factors known to be related to dopamine such as age (Tarita-Nistor et al.,
2006), visual acuity and luminance contrast have also been demonstrated to alter binocular rivalry rate in groups of individuals (Fahle, 1982; Hollins, 1980; Mueller,
1990; O’Shea, Blake, & Wolfe, 1994). It is acknowledged that our results do not argue against a role of serotonin per se, as the majority of participants with schizophrenia in our sample were taking medications that interact with both dopamine and serotonin receptors. Anti-psychotic medications vary in their serotoninergic and dopaminergic affinities, with some typical anti-psychotic drugs having little or no influence on serotonin (for example, Haloperidol) while other have specific Serotonin (5-HT2A) affinity (for example, Olanzapine) (Seeman, 2002).
Chapter 3: Slower Binocular Rivalry Rates in Individuals with Schizophrenia Compared to Healthy Controls105
While most antipsychotic agents block dopamine (for example, Risperidone), others are dopamine agonists (for example, Aripiprazole) (Seeman, 2002). Slower binocular rivalry rate may be associated with reduced dopamine release in the visual pathways, either by known dopaminergic processes within the primary visual pathways or by the stimulatory effect of serotonin receptors on striatal dopamine release.
3.7 Conclusion
The main finding of this study was that binocular rivalry rates were significantly slower in participants with schizophrenia than in healthy controls. This was evident for both low-strength and high-strength binocular rivalry stimuli.
However, no difference in binocular rivalry rate was found in the rate of perceptual alternations in a monocular task (Necker Cube). These data suggest that slow binocular rivalry rate is not specific to BPD as previously reported, but may be a feature of major psychiatric disorders more broadly. High-dose anti-psychotic medication affected binocular rivalry rate, suggesting that slow binocular rivalry rate may indicate increased dopamine release within the striatum or visual pathways.
This effect may be moderated by dopamine release.
Although not sensitive enough to separate diagnostic groups within those with schizophrenia, the binocular rivalry task may be an appropriate measure to include in a battery of tasks to investigate neurotransmitter involvement in psychosis including schizophrenia and other mental illnesses. It is also possible that there are more fundamental differences in binocular rivalry in schizophrenia that can be attributed to abnormal visual processing within specific visual pathways.
Differences within the ‘transient visual pathway’ (closely associated to the magnocellular system) and the ‘sustained visual pathway’ (associated with the
106Chapter 3: Slower Binocular Rivalry Rates in Individuals with Schizophrenia Compared to Healthy Controls
parvocellular visual system) (Bretmeyer & Ganz, 1976) require further exploration in this regard.
Chapter 3: Slower Binocular Rivalry Rates in Individuals with Schizophrenia Compared to Healthy Controls107
Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific
Abnormalities in Schizophrenia
4.1 Magnocellular and Parvocellular Pathways in Schizophrenia
The most prominent theory related to visual abnormalities in schizophrenia is the ‘Transient Channel Hypothesis’ (Breitmeyer & Ganz, 1976; Butler et al., 2003;
Green, Neuchterlein, Breitmeyer, Tsuang & Mintz, 2003; Keri, Antal, Szekeres,
Bebedek & Janka, 2000; Schechter et al., 2005). The Transient Channel Hypothesis proposes that the neuronal pathway that integrates dynamic visual information (i.e. the magnocellular pathway), such as the position and spatial relationships of visual stimuli and the attention-capturing mechanism, is impaired in schizophrenia. Over activity may interrupt the neural processing of the sustained (or parvocellular) visual pathway (Butler et al., 2003). There is general agreement that the anomalous perceptual abnormalities observed in schizophrenia (seen in both medicated and medication-näive first-episode schizophrenia) are associated with the heightened sensitivity of the magnocellular pathway (Kiss, Fabian, Benedek & Keria, 2010). It is possible that early visual processing deficits occur in both magnocellular and parvocellular systems; however it is considered that those with predominantly magnocellular input contribute to down-stream processing (Brittain, Surguladze,
McKendrick & Ffytche, 2010).
Transient visual-pathway (or magnocellular-pathway) abnormalities in schizophrenia have been reported to account for altered backward-masking task performance (Breitmeyer & Ganz, 1976; Butler et al., 2003; Candenhead et al., 1998;
Green et al., 1999; Green et al., 1994a, 1994b; Green et al., 2003; Keri et al., 2000;
Schechter, Butler, Silipo, Zemon & Javitt, 2003; Slaghuis, 1998, 2004), impaired motion-defined letter task performance (Schwartz et al., 1999a), inaccurate smooth
Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia 108
pursuit tracking (Schwartz et al., 1999b) and reduced amplitudes and increased latency of components of the transient visual-evoked potential (tVEP) (Schechter, et al., 2005).
Exploring binocular rivalry using stimuli that bias task processing to either the magnocellular or parvocellular pathways in this group of individuals provides a unique opportunity to explore the ‘visual pathway’ theories of binocular rivalry, while investigating further visual awareness functions in schizophrenia. While it is not possible to completely separate the magnocellular and parvocellular pathways during psychophysical testing, due to considerable inter-play between them
(Livingstone & Hubel, 1987; Shapley, 1992), it is possible to use binocular rivalry stimuli biased to preferentially stimulate either pathway. Changing the characteristics of stimuli used to bias the task to a particular anatomical visual pathway is an approach taken by other researchers using other neurophysiologic measures. For example, magnocellular and parvocellular selective stimuli have been used to elicit differential components in measuring tVEP (Crewther, Crewther,
Klistorner & Kiely, 1999; Foxe, Strugstad, Sehatpour, Molholm, Pasieka, Schroede,
& McCourt, 2008; Klistorner, Crewther, & Crewther 1996; Klistorner, Crewther &
Crewther, 1997; Lalor, Yeap, Reilly, Pearlmutter & Foxe, 2008; Schechter et al.,
2005) in backward-masking tasks (Breitmeyer & Ganz, 1976; Butler et al., 2003;
Cadenhead et al., 1998; Green et al., 1994a, 1994b; Green et al., 1999; Keri et al.,
2000; Schechter et al., 2003), in motion-defined letter tasks (Schwartz et al., 1999a) and in smooth pursuit tracking tasks (Schwartz et al., 1999b). Using tasks for selective biasing of the parvocellular and magnocellular systems is an approach that has been endorsed by the Cognitive Neuroscience Treatment Research to Improve
Cognition in Schizophrenia (CNTRICS) (Green et al., 2009).
Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia 109
4.1.1 Physiological differences in the magnocellular and parvocellular
pathways.
Parvocellular neurons show a sustained response when presented with long- duration stimuli. Magnocellular neurons respond to the same stimuli in a transient fashion, with only a brief burst of activity at stimulus onset and offset (Schwartz,
1999). These time-course differences suggest that parvocellular and magnocellular neurons play different roles in processing temporal information. The magnocellular neurons that constitute the transient (magnocellular) pathway have large axons that transfer information quickly to cortical areas (with conduction velocities of approximately 4 m/s (Kolb, Ferandez & Neslon, 2009), therefore are more suited to carry information regarding the onset and offset of stimuli. They respond rapidly to changes in illumination, and can resolve high-temporal-frequency stimuli and moving or flickering stimuli. Magnocellular-biased binocular rivalry stimuli should therefore be moving or flickering. However, the smaller parvocellular neurons of the sustained parvocellular pathway transfer temporal information more slowly (at conduction velocities of approximately 2 m/s (Kolb et al., 2009), so are best suited to code low temporal frequencies and stationary, or near-stationary, stimuli
(Livingstone & Hubel, 1988). Thus, stationary binocular rivalry stimuli are most appropriate to stimulate parvocellular processing.
In terms of the colour of the binocular rivalry stimuli, parvocellular neurons display colour opponency while magnocellular neurons do not (Shapley, 1992). That is, stimuli of a particular wavelength may either stimulate or inhibit parvocellular neurons, thus these cells are thought to play a large role in colour perception
(Schwartz 1999; Shapley, 1990). In contrast, the majority of magnocellular neurons show little or no colour opponency. The magnocellular neurons’ responses to a
110 Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia
stimulus are the same regardless of the wavelength; these cells are monochromatic and do not contribute to wavelength-based discriminations (Schwartz, 1999).
However, a small portion of magnocellular cells have an inhibitory mechanism selective to long wavelength red light (Shapley, 1990; Wiesel & Hubel, 1990; Wiesel
& Hubel, 1966). Therefore, red light inhibits some magnocellular processing
(Shapley, 1990). Using red stimuli for the parvocellular binocular rivalry (BR) task and colourless (black and white) stimuli for the magnocellular BR task exploits this property and allows greater relative separation of the pathways.
Magnocellular and parvocellular cells are 'tuned' (i.e. respond best) to objects of particular sizes or with particular spatial frequency distributions. Parvocellular cells are small (often referred to as midget cells) with small receptive fields (a term that describes the spatial properties of retinal ganglion cells) (Kolb et al., 2009). The smaller diameter of the parvocellular neurons manifest higher spatial frequency resolution, allowing these cells to discriminate the fine detail of a stimulus, including coding for colour and spatial detail. Magnocellular cells (parasol cells) are large cells with broader dendritic fields and larger receptive fields, and are less responsive to spatial detail. These large cells operate when there is low luminance contrast; that is when there is only a small difference in the brightness of the image compared to its background (Skottun & Skoyles, 2007). Therefore, using stimuli of high spatial frequency for the parvocellular binocular rivalry task and low spatial frequency stimuli for the magnocellular binocular rivalry tasks are appropriate.
Parvocellular cells are generally receptive to colour, but not to fast movement, and are concerned with the spatial detail of objects. Contrastingly, magnocellular cells are ‘colour blind’, sensitive to movement at low luminance contrast but do not possess fine spatial discrimination (Shapley, 1992). The transient (or magnocellular)
Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia 111
visual pathway is considered to be concerned with the ‘Where is it?’ component of vision, while the sustained (or parvocellular) visual pathway is concerned with the
‘What is it?’ component (Livingstone & Hubel, 1988; Schwartz, 1999). The experiments described in this chapter use binocular rivalry stimuli with different characteristics to produce a relative processing bias toward either the magnocellular or parvocellular system, as described in Section 4.2.1.1.
4.1.2 Magnocellular and parvocellular pathways in binocular rivalry.
There is debate about the nature of the binocular rivalry process, particularly in terms of localisation. There are two widely-held arguments: ‘pattern rivalry’ and
‘eye rivalry’ (reviewed in Blake, 2001 and Tong, 2001). Proponents of ‘pattern rivalry’ theories suggest that binocular rivalry occurs with competition between the monocular neurons in the extra striate visual cortex V1 (Blake, 1989) or in the lateral geniculate nucleus (LGN) (Lehky, 1988). Supporters of an ‘eye rivalry’ theory assert binocular rivalry arises from competition between the cortical representations of each image in higher visual cortical areas (Leopold & Logothetis, 1996;
Logothetis & Schall, 1989; Sheinberg & Logothetis, 1997). The ‘eye rivalry’ theory proposes that binocular rivalry occurs within both lower- and higher-visual processing areas, and that binocular rivalry is a consequence of the actions of either the magnocellular (Livingstone & Hubel, 1987) or parvocellular visual pathways
(Carlson & He, 2000; He et al., 2005). This view suggests that binocular rivalry results from neuronal processes that occur at all stages of visual processing. This includes magnocellular and parvocellular cells in the monocular neurons of the
LGN, superior colliculi (Livingstone & Hubel, 1988) and V1, as well as higher processing areas in the cortex, such as the ventral and dorsal streams carrying information to parietal and temporal cortical areas (Wandell, 1995).
112 Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia
The findings of the few studies that have investigated magnocellular and parvocellular pathway contributions to binocular rivalry have not been consistent
(Blake, 2001). For example, Hollins and Hudnell (1980) speculated that rivalry was dependent on the transient or magnocellular pathway, as the spatial frequencies of patterns that resulted in the strongest rivalry percept were within the range usual for magnocellular processing. This notion was supported by Livingstone and Hubel
(1987) who found that stimuli with characteristics thought to be processed via the parvocellular pathway yielded fusion rather than rivalry. To further support the case for magnocellular involvement, rivalry occurs for competing stimuli presented at alternation rates that favour the magnocellular pathway (Blake & Boothroyd, 1985).
Furthermore, rivalry can occur between competing motion after-effects (Blake, et al.,
1998) which are generally thought to arise from magnocellular processing (Tootell et al., 1995). However, some studies using stimuli that strongly activate the magnocellular pathway have failed to generate rivalry (Liu et al., 1992; O’Shea &
Blake, 1986) or have (at best) yielded weak rivalry (Carlson & He, 2000).
Furthermore, the work of Kulikowski, (1992) and O’Shea (1996) demonstrated that stimuli that are processed primarily by the parvocellular pathway could yield clear, crisp rivalry, and stimuli with luminance contrasts above the saturation of magnocellular cells also produced crisp binocular rivalry (Alexander, 1951; Levelt,
1965, 1967). Flickering stimuli (Wade, 1975; Wolfe, 1983a; Wolfe, 1983b), and those that differ in the temporal characteristics of two stimuli, tend to fuse (O’Shea
& Blake, 1986) whereas colour conflict stimulates crisp binocular rivalry
(Kulikowski, 1992; Wade, 1975). This also suggests that parvocellular pathways are involved in binocular rivalry (He et al., 2005). The observation that motion information can be integrated at the same time as form rivalry (Andrews &
Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia 113
Blakemore, 1999; Carlson & He, 2000) and colour rivalry (Carney et al., 1987) has led to the hypothesis that both pathways are necessary for binocular rivalry (He et al., 2005).
This chapter is divided into two sections. The first measures binocular rivalry rates and dominance durations in participants with schizophrenia and healthy controls, using visual stimuli biased towards the magnocellular and parvocellular visual pathways. The second compares this binocular rivalry task with a visual backward-masking task, a task that has been used extensively to investigate magnocellular pathway abnormalities in participants with schizophrenia (Butler et al., 2003; Cadenhead et al., 1998; Green et al., 1994b; Green, Nuechterlein,
Breitmeyer & Mintz, 2005; Green, Nuechterlein, Breitmeyer & Mintz, 2006). A model of binocular rivalry is proposed based on the sustained-transient theory of visual backward masking.
4.2 Study 3, Experiment 1: Assessing Binocular Rivalry in Schizophrenia Using
Stimuli that Bias the Magnocellular and Parvocellular Visual Pathways
The aim of the first study was to measure binocular rivalry rates in participants with schizophrenia and healthy controls, using visual stimuli biased towards the magnocellular and parvocellular visual pathways. It was predicted that binocular rivalry rates in participants with schizophrenia would be slower than that of healthy controls, with the greatest abnormality observed using stimuli biased towards the magnocellular pathway, given that deficits in the magnocellular pathway are reported in schizophrenia (Breitmeyer & Ganz, 1976; Butler et al., 2003; Cadenhead et al.,
1998; Keri et al., 2000; Green et al., 1999; Green et al., 1994a, Green et al., 1994b;
Green et al., 2003; Schechter et al., 2003; Schechter et al., 2005; Schwartz et al.,
1988; Schwartz et al., 1999b, Slaghuis, 1998; Slaghuis, 2004).
114 Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia
4.2.1 Method.
4.2.1.1 Participants with schizophrenia.
Twenty individuals with schizophrenia, who participated in the study described in Chapter 3, were recruited to the study; however three were excluded due to insufficient contrast sensitivity to reliably perform the magnocellular BR task, leaving 17 remaining participants. Six participants met the schizophrenia sub-type classification of paranoid schizophrenia, with the remaining 11 categorised as undifferentiated schizophrenia sub-type (Structured Clinical Interview for the DSM-
IV). Six participants had positive symptoms of schizophrenia, nine had negative symptoms and two had equal positive and negative symptoms as assessed by the
PANSS (Kay et al., 1988). Fourteen participants were taking atypical anti-psychotic medication (four taking Olanzapine, three taking Risperidone, five taking Clozapine, one taking Quetiapine and one taking Amisulphride) and three were taking typical anti-psychotic medication. The CPZEs of their dosages ranged from 200-800 mg/day, with the average being 479.4 mg/day. All participants had normal vision and
6/6 visual acuity (corrected or uncorrected) in each eye, as assessed by Snellen visual acuity testing.
4.2.1.2 Control participants.
Twenty-five control participants were recruited to the study. Of the 25 control participants, 17 had participated in the study described in Chapter 2, and eight new participants were recruited. One male participant was excluded as he had insufficient contrast sensitivity to reliably perform the magnocellular BR task leaving 24 participants. All participants had normal vision and 6/6 visual acuity
(corrected or uncorrected) in each eye measured by Snellen visual acuity testing.
Participant characteristics are detailed in Table 4.1.
Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia 115
Table 4.1: Age, gender, eye dominance and NART score of participants with schizophrenia and controls
Controls Schizophrenia χ2 df p (n=24) (n=17) Age Mean (yrs) 38.4 36.5 Range 21-64 23-54 24.382 23 0.383 Gender Male 4 13 Female 20 4 14.664 1 <0.001 Eye Dominance R)eye 15 11 L)eye 9 6 0.021 1 0.575 NART Score Mean 116.4 113.7 Range 102-122 101-124 19.514 16 0.243
4.2.1.3 Binocular rivalry stimuli to bias the magnocellular and parvocellular
pathways.
The binocular rivalry stimuli were presented in the same manner as described in Chapter 2 (Section 2.2.2.1). The stimuli to bias task processing to the magnocellular pathway (herein referred as magnocellular BR stimulus) consisted of achromatic horizontal and vertical lines of low spatial frequency (1 cpd), at low luminance contrast (8%) moving at approximately 4 Hz presented in a circular aperture measuring 1.5 degrees of visual angle. The stimuli biasing the task to the parvocellular pathway (herein referred to as parvocellular BR stimulus) consisted of stationary red vertical and horizontal lines of high spatial frequency (10 cpd) and at high luminance contrast (90%). Red vertical and horizontal lines were chosen for the parvocellular BR tasks as it been demonstrated that red light or red backgrounds can suppress magnocellular neural function (Bedwell, Brown & Miller, 2003;
Breitmeyer & Williams, 1990; Breitmeyer & Breier, 1994; Edwards, Hogben, Clark
& Pratt, 1996; Pammer & Lovegrove, 2001; Skottun, 2004).
116 Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia
While every effort has been made to produce binocular rivalry stimuli that bias the magnocellular and parvocellular pathway, complete separation cannot be assured. It is difficult to produce a stimulus that biases only the parvocellular visual system as the two pathways overlap in their spatial frequency selectivity (Ellemberg,
Hammarrenger, Lepore, Roy & Guilemot, 2001). Although the sensitivity of magnocellular neurons is lower than parvocellular neurons at higher spatial frequency, allowing free eye movements which generate transients suggests that the magnocellular neurons may potentially respond to the stimuli presented in the parvocellular BR task.
4.2.1.4 Recording binocular rivalry.
Each participant completed three two-minute blocks of binocular rivalry using the magnocellular- and parvocellular-biased binocular rivalry stimuli described above. The methods for recording the binocular rivalry data were the same as described previously in Chapter 2 (see Section 2.4, procedure).
4.2.2 Statistical analyses.
A power analysis was performed to determine the minimum number of participants required to demonstrate a difference in binocular rivalry rates between the two groups. The findings from the studies presented in Chapters 2 and 3 were entered into the G*power3 program (Faul et al., 2007). It was estimated that a sample size of 14 in each group was required for a two-sided 5% significance level and power of 80 to demonstrate a difference in binocular rivalry rate in the magnocellular and parvocellular BR tasks in the two groups.
The effects of group, gender, age, education and NART score on binocular rivalry rate were determined by Kruksal-Wallis one-way non-parametric analyses of variance. Planned comparison Mann-Whitney U tests were performed to determine
Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia 117
the differences in binocular rivalry rate between participants with schizophrenia and controls in both the magnocellular and parvocellular BR tasks. Analyses of three factors unique to the schizophrenia group (diagnostic sub-group, dose of antipsychotic medication measured in CPZEs, and positive and negative symptoms of schizophrenia) were conducted, to more-fully examine influences on binocular rivalry rate in participants with schizophrenia. These contrasts utilised the Mann-
Whitney U test.
Dominance durations, i.e. the time between button pushes (time intervals spent viewing horizontal lines and vertical lines) were normalised for each participant (by dividing each time interval by the grand mean for each participant) and then each group was compared using the Smirnov test (Conover, 1971). The resulting distributions were considered significant at the p<0.05 level of significance where α is if T1 exceeds its 1 – α quantile. The 0.95 quantile of T1 is given by w0.95 ≈1.36√ m+n/ mn (Conover, 1971) (see previous chapter, Section 2.5.1 for details).
4.2.3 Results.
4.2.3.1 Binocular rivalry rate.
There was a significant between-group difference in binocular rivalry rate for both the magnocellular and parvocellular BR tasks (χ2 [1, 41] = 10.6-6, p = .001 in the magnocellular BR task and χ2 [1, 41] = 14.761, p < .001 in the parvocellular BR task). Gender also had an effect on binocular rivalry rate in both tasks, with males showing slower rates (magnocellular BR task gender χ2 [1, 41] = 4.486, p = .034 and parvocellular BR task χ2 [1, 40] = 9.775, p= .002). Age and NART score had no effect on binocular rivalry rate in either task (age; magnocellular BR task χ2 [1, 23] =
21.283, p = .564, parvocellular BR task χ2 [1, 23] = 23.383, p <.283, and NART;
118 Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia
magnocellular BR task χ2 [1, 15] = 17.557, p = .287, parvocellular BR task χ2 [1, 15]
= 17.206, p = .307).
In the magnocellular BR task, binocular rivalry rates were significantly slower in the group with schizophrenia (n = 17, mean rate 0.22Hz, SD= 0.11) compared to healthy controls (n = 24, mean rate 0.38Hz, SD=0.17, Z = -3.257, p< .001).
Participants with schizophrenia were on average 0.16 Hz slower than healthy participants (range group with schizophrenia 0.092-0.438 Hz; healthy 0.192-0.775
Hz) in the magnocellular BR task. Those with schizophrenia also recorded significantly slower binocular rivalry rates in the parvocellular BR task (n = 17, mean rate 0.24Hz, SD= 0.09) compared to controls (n = 24 mean rate 0.46Hz, SD=
0.22, Z = -3.842, p< .001). Participants with schizophrenia were 0.22 Hz slower than control participants on average (range for schizophrenia 0.125-0.392 Hz, healthy participants 0.217-1.050 Hz) in the parvocellular BR task. These data are presented in Figure 4.1.
Control participants recorded significantly faster binocular rivalry rates in the parvocellular, compared to the magnocellular BR task (n = 24), mean rate 0.457 Hz,
SD = 0.22 compared to 0.384 Hz, SD = 0.17 respectively (Z = -2.387, p =. 017).
This effect was not observed in the participants with schizophrenia, (n = 17) mean rate 0.237 Hz, SD = 0.088 compared to 0.224 Hz, SD = 0.113 respectively (Z = -
0.621, p =. 535).
Planned comparisons revealed that females recorded significantly faster binocular rivalry rates than males in both tasks. For the magnocellular BR task, the oscillation rate was 0.64 Hz for females (n =2 4, M = 0.636 Hz, SD = 0.178) and 0.25
Hz for males (n = 17, M = 0.253Hz, SD = 0.137; Z = -2.188, p = .034). For the parvocellular BR task the rate was 0.45 Hz in females (n = 24, M = 0.445 Hz, SD =
Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia 119
0.23) and 0.25 Hz in males (n = 17, M = 0.254 Hz, SD = 0.07; Z = -3.127, p = .002).
Females recorded significantly faster binocular rivalry rates in the magnocellular BR tasks than in parvocellular BR tasks (Z = -2.601, p = .009), however no differences were found in magnocellular verses parvocellular binocular rivalry rates in males (Z
= -0.388, p = .698). Females with schizophrenia (n = 4) recorded slower binocular rivalry rates in the parvocellular BR task (n = 4, M = 0.191 Hz, SD = 0.06) than healthy controls (n = 20, M = 0.495 Hz, SD = 0.217) (Z = -2.983, p < .001), but not in the magnocellular BR task (M = 0.249 Hz, SD = 0.175 compared with M =
0.249Hz, SD = 0.161, Z = -1.822, p = .068). The low participant numbers in some sub-groups warrant a cautious interpretation of these findings.
Schizophrenia (n=17) Healthy Control (n=24)
0.6
0.5 0.457 0.4 0.384 0.3
BR in Hz BR Rate 0.224 0.237 0.2 (button pushes/sec) (button
0.1
0 Magnocellular BR Task Parvocellular BR Task
Figure 4.1: Binocular rivalry rates recorded in participants with schizophrenia (black triangles) compared to healthy controls (black diamonds).
Diagnostic sub-group, medication dose and negative and positive symptoms of schizophrenia had no effect on binocular rivalry rates in either the magnocellular or parvocellular tasks in participants with schizophrenia (Mann-Whitney U tests).
Diagnostic sub-group (paranoid schizophrenia [n = 6] versus undifferentiated schizophrenia [n = 11] ); magnocellular BR task (Z = -0.453, p = .66) and
120 Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia
parvocellular BR task (Z = -0.605, p = .591), low (<425 mg, n = 8) versus high dose
(>425mg, n = 9) of anti-psychotic medication (quantified higher or lower than median dose in CPZEs; magnocellular BR task (Z = -1.398, p = .167) and parvocellular BR task (Z = -0.097, p = .963), and positive symptoms (n = 6) versus negative symptoms (n = 9); magnocellular BR task (Z = -1.003, p = .328) and parvocellular BR task (Z = -0.413, p = .689). Two participants had equal positive and negative scores, and were excluded from the analyses.
4.2.3.2 Dominance intervals.
One-way Smirnov tests revealed significant differences in the distribution of normalised dominance intervals of participants with schizophrenia compared with healthy controls in both the magnocellular BR task and the parvocellular BR task
(Table 4.2).
Table 4.2: Smirnov test results indicating differences in the distribution of dominance durations between participants with schizophrenia (n=17) and controls (n=24) for both magnocellular and parvocellular binocular rivalry (BR) tasks.
. Schizophrenia Control Critical Value - Smirnov Reject Ho? m n Smirnov Test T Reject if 1.36√ m+n/ mn T1>CV- (T1) ST Magnocellular 1551 3978 0.070515 0.115485 Yes BR Task
Parvocellular 1494 3342 0.07331 0.096773 Yes BR task
As can be seen in Table 4.2, there were significant differences in the distribution of dominance intervals produced in both the magnocellular and parvocellular BR tasks at the p < 0.05 level. The greatest differences in the distribution functions for both magnocellular and parvocellular BR tasks occurred at
Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia 121
the 0.5 second time interval, as seen in Figure 4.2. This reflects significantly more dominance intervals of 0.5 seconds in duration being recorded in participants with schizophrenia. It is notable that although participants with schizophrenia recorded more dominance durations of less than one second in the magnocellular BR task, they recorded fewer dominance durations from 1.5 to 4 seconds compared to those recorded in controls, resulting in a slightly flatter distribution (Figure 4.2a). A significant separation between any two points on each curve indicates a significant difference in mean normalised dominance durations. There are significant differences in the number of dominance durations recorded of 0.5 seconds for both the magnocellular and parvocellular BR tasks.
4.2.4 Discussion related to magnocellular and parvocellular tasks.
4.2.4.1 Binocular rivalry rates.
Binocular rivalry rates recorded by participants with schizophrenia were significantly slower for both the magnocellular and parvocellular BR tasks (p <
.001). Slower binocular rivalry rates (or increased mean dominance intervals) in participants with schizophrenia have been reported elsewhere (Fox, 1965; Frecska,
White et al., 2003; Sappenfield & Ripke, 1961; White et al., 2001; Wright et al.,
2003), suggesting a general finding of slower binocular rivalry rates in schizophrenia. These data suggest an overall visual abnormality in binocular rivalry consistent with the findings of backward masking, motion-defined letter tasks, smooth pursuit eye movement tracking tasks and VEPs (Breitmeyer & Ganz, 1976;
Butler et al., 2003; Cadenhead et al., 1998; Green et al., 1999; Green et al., 2003;
Green et al., 1994a, 1994b; Keri et al., 2000; Schechter et al., 2003; Schechter et al.,
2005; Schwartz, 1999a 1999b; Slaghuis, 1998; Slaghuis, 2004). In this study the greatest difference in binocular rivalry rates between participants with schizophrenia
122 Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia
and healthy controls was recorded in the parvocellular BR task, rather than the magnocellular BR task (difference in binocular rivalry rate of 0.22 Hz compared to
0.16 Hz).
Some authors have suggested that the parvocellular visual pathway is responsible for binocular rivalry (Carlson & He, 2000; He et al., 2005; O’Shea &
Williams, 1996), however one earlier study suggested the opposite (Livingstone &
Hubel, 1987). Therefore, it would be expected that stimuli that bias the binocular rivalry task to the parvocellular pathway would yield crisp alternations of opposing images, with few composite images, and thus a faster alternation rate. Conversely, stimuli that bias the binocular rivalry task to the magnocellular pathway would be expected to elicit more mixed images where the vertical and horizontal lines attempt to fuse into a stable percept, leading to longer inter-stimulus intervals and a slower binocular rivalry rate. It can be seen from Figure 4.1 that control participants recorded significantly faster binocular rivalry rates in the parvocellular BR task compared to the magnocellular BR task (magnocellular and parvocellular BR tasks respectively; M = 0.38 Hz, SD = 0.17 and M = 0.46 Hz, SD = 0.22, Wilcoxon signed ranks test Z = -2.387, p = .017), which is consistent with the binocular rivalry literature.
4.2.4.2 Dominance duration intervals.
There was a significant difference (p< .05) in the distribution of dominance durations recorded by participants with schizophrenia compared to healthy controls in both binocular rivalry conditions (Conover, 1971). Participants with schizophrenia recorded significantly more short dominance durations of less than one second (see Figures 4.2a and 4.2b), resulting in an overall statistical difference in the distribution of dominance durations between the two groups, and less dominance
Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia 123
durations between 1.5 to 4 seconds. This was reflected in a flatter dominance distribution curve. The short dominance durations recorded in participants with schizophrenia did not correlate with faster alternations of rivalling images (i.e. the binocular rivalry rate). In fact, participants with schizophrenia recorded significantly slower binocular rivalry rates in both binocular rivalry tasks compared to control participants. This is likely due to the greater number of dominance durations greater than 4 seconds recorded by participants with schizophrenia in each task. a.
Cumulative Frequency Normalised Dominance Durations - Magnocellular BR Task
1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 Cumulative Probability Cumulative 0.1 0.0 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6 6.5 7 7.5 8 8.5 9 Time in seconds Schizophrenia Controls b.
Cumulative Frequency Normalised Dominance Durations - Parvocellular BR Task
1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 Cumulative Probability 0.1 0.0 00.511.522.533.544.555.566.577.588.59 Time in Seconds . Schizophrenia Controls
Figure 4.2: Difference between the dominance durations of participants with schizophrenia (n=17) (black lines) and control participants (n=24) (grey lines) for (a) the magnocellular binocular rivalry (BR) task and (b) the parvocellular BR task.
124 Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia
These data are consistent with the idea that individuals with schizophrenia have abnormal processing in both the magnocellular and parvocellular visual pathways. If magnocellular processing is ‘overactive in individuals with schizophrenia, they would be likely to perceive more visual information arising from short bursts of activity of the magnocellular neurons, interrupting parvocellular processing further along the visual pathway. This would result in more frequent short dominance durations. Abnormalities in parvocellular processing may account for the abnormally long dominance durations in the schizophrenia group that act to slow the binocular rivalry rate.
The method of binocular rivalry recording employed here requires that participants ignore mixed or composite images and only record the change in perception to the opposing image (that is, to record the change from a horizontal or mixed image to one that is exclusively vertical, or a vertical or mixed image to one that is exclusively horizontal). There are few stimuli that will produce perfect binocular rivalry alteration of opposing images. Generally all participants experiencing binocular rivalry perceive alternation of opposing images interspersed with periods of mixed or composite image (Burke et al., 1999; Liu et al., 1992;
Mueller & Blake, 1989). As this experiment presented opposing images to each eye in a continuous fashion, the parvocellular system had sufficient time to process the spatial and chromatic details of stimuli to produce fast, crisp binocular rivalry alternations. It has been posited that that one of the functions of the magnocellular pathway may be to gate parvocellular signals to the cortex (Shapley, 1992) (based on the observation that the detection of iso-luminant colour patterns is facilitated by luminance patterns (Switkes, Bradely & De Valois, 1988). It is possible that the magnocellular pathway simultaneously attempts to fuse the images into a single
Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia 125
percept based on the temporal and luminance properties of the images. Thus the resulting phenomenon is a period where a single stable image is perceived, followed by a period of mixed image before a change in perception of the alternative image.
Binocular integration and binocular rivalry have been demonstrated to coexist in the same spatial location in the visual pathways (Carlson & He, 2000). Carlson and He (2000) demonstrated that observers were able to perceive binocular rivalry with respect to the colour and shape of the opposing triangles, while integrating two temporal frequencies into a ‘slow flicker’ amplitude modulation (beat) using information from the suppressed stimulus. It is accepted that two flickering frequencies close together do not lead to binocular rivalry in participants with normal stereovision; rather a slow flicker amplitude modulation (beat) that corresponds to the difference between the primary frequencies is seen (Baitch & Levi, 1989; Karrer,
1967). These observations were explained by the authors as being the consequence of the independent processing of the different attributes in the magnocellular and parvocellular pathways. They posited that the parvocellular pathway, which preferentially processes information regarding colour and shape of the stimulus, leads to binocular rivalry. Carlson & He (2000) and He et al., (2005) suggest that because the magnocellular pathway was more likely responsible for processing flicker and temporal features of the stimulus that leads to fusion. Both of these phenomena could occur at the same time within the same visual location. It could be argued that the two visual pathways contribute to binocular rivalry, but are both necessary to process the opposing images presented in binocular rivalry tasks. It can be seen that participants with schizophrenia and controls were able to maintain crisp perceivable binocular rivalry in both stimulus conditions. Therefore, if both pathways contribute to the alternation of perceptual images seen in binocular rivalry
126 Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia
it may be the case that they occur between processes well beyond V1, and after the computations between stimuli attributes have occurred.
It is possible that significant differences in binocular rivalry rates recorded by participants with schizophrenia for both the magnocellular and parvocellular BR tasks demonstrate an abnormality in both pathways, as there is considerable interplay between the pathways. Although the pathways have been discussed as being quite distinct, they do interact higher in the visual pathway, in particular in V1 and V2 of the visual cortex (Shapley, 1990; Livingstone & Hubel, 1987). Schizophrenia researchers have suggested cognitive disability is related to parvocellular pathway functioning (Vidyasagar, 1999), while the magnocellular input may be vital for controlling sequential attention (Kessels, Postma & de Haan, 1999). Hyperactive magnocellular pathways have also been proposed as being responsible for some anomalous perceptual experiences, including abnormal intensity of environmental stimuli, feelings of being flooded and inundated and the inability to focus attention on relevant details (Keri & Bemedek, 2007).
4.2.4.3 Gender differences.
There is little published research reporting gender differences in binocular rivalry, with two studies reporting that females recorded faster binocular rivalry rates than males (Cogan, 1973; Goldstein & Cofoid, 1965). Data from developmental studies (Gwiazda, Bauer, & Held, 1989) indicate that female infants prefer to view a rivalrous stimulus (rather than a fusible stimulus) until a mean age of 9.9 weeks; this preference ceasing significantly earlier than in male infants (averaging 13.8 weeks).
Similarly, females showed evidence of stereopsis at an earlier age (9.1 weeks, compared with 12.1 weeks for males). No studies could be located where males were reported to have faster binocular rivalry rates than females. Miller et al., (2003)
Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia 127
found no overall gender effects in their sample of 18 participants with schizophrenia
(males n = 9, females n = 9). Gender effects in subjects with schizophrenia were not reported in Sappenfield and Ripke (1961), males n = 21, females n = 9, Fox (1965) males n = 10, females n = 5, and White et al., (2005) males n = 21, females n = 3.
The gender of 24 participants with schizophrenia tested in Frecska et al., (2003) was not specified. Although statistically significant, the gender differences found in the current study require replication, given the small number of female participants with schizophrenia included in the sample (n = 4).
It is possible that the gender-related differences in binocular rivalry observed here are due to hormonal changes associated with the menstrual cycle. The actions of oestrogen, progesterone, and androgen have been suggested to contribute to improved colour vision performance at ovulation (Giuffre, Di Rosa & Fiorino,
2007), increases in visual sensitivity during menstruation (Barris, Dawson & Theiss,
1980) and decreases in pattern reversal evoked potentials (Yilmaz, Erkin, Mavioglu
& Sungurtekin, 1998). Hormonal changes, and the use of oral contraceptives, have been linked to alterations in retinal function and sensitivity changes in some women
(Eisner, Burkes & Toomey, 2004), however these alterations are not the same for all visual pathways, and there were pronounced individual differences with individual’s visual adaptation capabilities varying substantially over periods of weeks (Eisner et al., 2004). The gender effect observed in the current study may be related to hormonal effects in the small number female participants included in the sample.
Future studies should control for menstrual cycle variations or use of the contraceptive pill.
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4.3 A Backward-Masking Task Utilising Stimuli that Bias the Magnocellular and
Parvocellular Visual Pathways
4.3.1 Introduction.
Based on a comprehensive review of published literature, no binocular rivalry studies were identified that used a similar method employing stimuli that bias the magnocellular and parvocellular visual pathways outlined in Experiment 1 (Section
4.2). Consequently, there are no normative data with which to compare the results presented in Section 4.2. The current study conducted to validate these results using another visual task that is widely accepted to reliably bias the magnocellular and parvocellular visual pathways, using a ‘within-subject design’.
4.3.1.1 Comparing binocular rivalry with other neurophysical tasks.
A search of the literature revealed that a variety of methods have been used to investigate magnocellular and parvocellular processing in schizophrenia. These include: contrast sensitivity tasks (Keri & Benedek, 2007; Slaguis, 1998), luminance- flicker sensitivity (Slaghuis & Bishop, 2001) luminance discrimination tasks
(Delord et al., 2006), random dot patterns and global motion tasks (Chapman, Hoag
& Giaschi, 2004), spatial alignment of dots and gratings and frequency-doubling
(Keri et al., 2004), smooth pursuit tracking where participants were asked to track dots moving a varying speeds (Schwartz et al., 1999b) and visual backward masking
(Bedwell & Orem, 2008; Birch, 1997; Butler et al., 2003; Buttner et al., 1999;
Cadenhead et al., 1998; Green et al., 1994b; Birch, 1997; Green et al., 2003; Green et al., 2005; Green et al., 2006; Holzman, 1987; Keri et al., 2000; Keri, Benedek et al.,
2001; Keri, Szendi et al., 2001; McClure, 2001; Slaghuis & Curran, 1999; Weiss,
Chapman, Strauss & Gilmore, 1992). There have also been a number of electrophysiological studies; VEPs (Butler et al., 2001; Butler et al., 2005; Butler et
Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia 129
al., 2007; Schechter et al., 2005), event related potentials (ERPs) (Butler et al., 2007;
Doniger et al., 2002), along with functional MRI (Martinez et al., 2008).
Visual backward-masking (VBM) tasks have been used most extensively, with many researchers reporting transient channel or magnocellular pathway abnormalities in participants with schizophrenia (Butler et al., 2003; Cadenhead et al., 1998; Green et al., 1994b; Green et al., 2005; Green et al., 2006). Some authors suggest both pathways are abnormal in participants with schizophrenia (Green et al.,
2003; Keri et al., 2000; Slaghuis & Curran, 1999), unaffected siblings (Birch, 1997;
Green et al., 2005), remitted patients (Butler et al., 2003; Buttner et al., 1999), and individuals prone to psychosis. Backward masking is thus a promising indicator of vulnerability to schizophrenia, with backward-masking abnormalities being suggested as a trait marker for the disease (Bedwell & Orem, 2008; Buttner et al.,
1999; Green et al., 1997; Holzman, 1987; Keri, Benedej et al., 2001; Keri, Szendi, et al., 2001; McClure, 2001).
There are a number of attributes of VBM that make this an attractive task to compare with binocular rivalry. Firstly, the stimulus characteristics of the task can be altered to bias the task for processing via the magnocellular or parvocellular pathways with the use of colour, luminance contrast, and movement in a similar way to binocular rivalry. The VBM task can be presented to participants using a computer and response keypad with minimal specialist training required for the researcher. Both binocular rivalry and visual backward masking involve suppression of one image and dominance of an alternative image (image presented to the left versus right eye in binocular rivalry, the target by the mask in VBM), and abnormal visual processing has been demonstrated in participants with schizophrenia.
130 Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia
4.3.1.2 Development of the visual backward masking task.
A VBM task was developed based on the task described in Cadenhead et al.,
(1998). Like Cadenhead et al, (1998) a location task for process bias via the magnocellular visual system (transient pathway) and an identification task for process bias via the parvocellular visual system (sustained pathway) was adopted.
Identification versus location VBM tasks along with centrally- or peripherally- located tasks have been used by others in VBM research (Koelebeck, Ohrmann,
Hetzel, Arolt & Suslow, 2005: Saccuzzo, Cadenhead & Braff, 1996). To further bias the location task to the magnocellular pathway, dark grey letters (chromaticity x= 0.2751, y= 0.3262, luminance 7.155 cd/m2) were presented at four spatial locations on a lighter grey background with a 6.9% luminance contrast (chromaticity x= 0.2756, y= 0.331, luminance 8.245 cd/m2). To further bias the task for the parvocellular (sustained) pathway red letters (chromaticity x= 0.2967, y= 0.5853, luminance 2.306 cd/m2) that were 30 pixels (or 8 mm high) were presented centrally on a green iso-luminant background (chromaticity x=0.5548, y=0.3883, luminance
2.306 cd/m2). Iso-luminance was determined by flashing a test patch of the red and green patches available on the computer at temporal frequencies of around 20 Hz the point at which the flicker cannot be detected. When green and red are of equal luminance, rather than perceiving flashes of green and red, a yellow sheen results
(this is a minimum flicker test) (Anstis & Cavanagh, 1983; Dobkins, Gunther &
Peterzell, 2000). The author and the programmer acted as participants in the preliminary testing during the development of the backward-masking tasks.
The target letters used in Cadenhead et al., (1998) were changed from A, V, W and Y to A, V, Y and T as the target letter W was spatially larger to the other three letters and was unable to be sufficiently masked. Cadenhead et al., (1998) used
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overlapping upper case Xs as the mask. Limitations in the software allowed for only a single letter or symbol to be used as the mask in our task, so overlapping Xs were not able to be achieved. A single upper-case letter X masked the V and the Y more effectively than it did the A or T, allowing for the A and T to be more readily identified in preliminary testing by both the author and programmer. Each letter and symbol on the computer keyboard was then trialled as the mask letter/symbol. This showed that the upper case S masked the target letters to the same degree and yielded more consistent results, with A, T, V and Y targets being identified with equal proficiency by the author and programmer.
The resulting VBM task was presented on a standard colour computer monitor in two conditions; an identification task to bias the parvocellular pathway (herein referred to as the parvocellular VBM task) and a location to bias the magnocellular pathway (herein referred to as the magnocellular VBM task). The target stimuli in each task consisted of one of four letters (A, T, V, or Y) presented either centrally in the parvocellular VBM task, or in one of four locations (up, down, left or right) in the magnocellular VBM task. The targets were presented at 2.1 degrees of visual angle from the fixation point (a small black +). The mask consisted of the letter S that was of equal size to the target letters, positioned so that it spatially overlapped the target stimuli, centrally in the parvocellular VBM task and in the all four possible locations in the magnocellular VBM task. In order to keep the VBM task as close to the binocular rivalry tasks as possible, the target letters and masks were presented for the same duration in each task. This differed from the tasks administered by
Cadenhead et al., (1998), who used an equal-strength target and mask in the identification task but increased the energy of the mask in the location task by presenting the mask for double the duration of the target. In the current study, the
132 Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia
duration of the target stimuli and the mask was 10 msecs. The mask was presented after each target letter (A, T, V, or Y) or in all locations (up, down, left or right) at four different inter-stimulus intervals (ISI); 27, 53, 107 and 213 msec (rounded up to the nearest frame during presentation). Letter/letter location and inter stimulus interval were counterbalanced over the duration of the task resulting in 64 trials of stimulus target followed by mask. In each trial a fixation point was presented on the screen (for 10 msec) following a short tone to indicate the onset of each trial.
4.3.1.3 The visual backward masking task procedure.
Written instructions were developed to ensure that each participant was given the same information (see Appendix 1 and 2).
A pilot test to trial the backward-masking task was undertaken. Five participants took part in the pilot test; all participants were female, aged between 27 and 40 years (average age 36.8 years). All were right handed and right-eye dominant
(as determined by a keyhole task), with 6/6 visual acuity.
Each participant completed 256 trials (representing four runs) of both the magnocellular VBM task and parvocellular VBM tasks. In the parvocellular VBM task the mask (S) was presented after each target letter (A, T, V, or Y) at four different inter-stimulus intervals; 27, 53, 107 and 213 msec. This allowed each target letter to be presented at each inter-stimulus interval on 16 occasions. Letters and inter-stimulus intervals were counterbalanced over the duration of the task.
Similarly, in the magnocellular VBM task the mask was presented after the target location (up, down, left or right) at four different inter-stimulus intervals; 27, 53, 107 and 213 msec, and counterbalanced over the duration of the task.
Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia 133
4.3.1.4 Results of preliminary testing.
In the magnocellular VBM task each participant identified the correct location of each target more than 80% of the time (see Table 4.3). Paired sample t-tests revealed no significant differences in the number of correct scores between the four target locations in the magnocellular VBM task (t > 0.05). However, in the parvocellular VBM task the letters A and V were correctly identified more than 80% of the time, while the letters T and V were more difficult to locate with correct scores of less than 80%. Paired t-tests revealed that there were significant differences in the number of correct scores when comparing A and T (t = 4.0 df = 4, p = .016) and A and Y (t = 3.64, df = 4, p = .022).
Although there was a significant difference in correct scores between the letter
A and the letters T and Y, it was decided not to change the target or the mask as preliminary testing identified these letters as the optimal letters to be used within programming limitations.
A significant practice effect was seen where each of the five participants were able to almost complete each task without error (reaching a ceiling for near-perfect scores) in the last 64 trials. A significant improvement in the scores was observed when comparing the first 64 trials with the last 64 trials in our group; 201 out of a possible 320 (5 x 64 trials) correct scores (62.5%) in the first 64 trials compared with
310 (96.87%) in the last. This practice effect reflects what is reported in the literature
(Maehara & Goryo, 2003; Wolford, Marchak & Hughes, 1988; Braffin Saccuzzo,
Ingram, McNeill & Langford, 1980). These five pilot participants were excluded from the later comparison between binocular rivalry and VBM tasks.
134 Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia
Table 4.3: Correct target letter identification by location and letter in a preliminary test of the magnocellular and parvocellular visual backward masking (VBM) task (n = 5).
Magnocellular VBM task Parvocellular VBM task
Location of Target Correctly identified Target Letter Correctly Identified
Down 85% A 93.75%
Left 87.5% T 73.75%
Right 86.25% V 86.25%
Up 81.25% Y 61.25%
Because the VBM tasks were designed to be at (or near) visual threshold, it was expected that nãive participants would not be able to achieve scores of 100% correct. A practice non-masking task was developed to ensure that participants had adequate contrast sensitivity to complete the task, and so that that each participant understood the task and could accurately identify the targets without introducing a practice effect. During the development of this task it was evident that the target letters used in the parvocellular VBM task were more easily identified than the letters of the magnocellular VBM task. In order to simplify the magnocellular VBM task to improve the consistency of results, the target letters could either be darkened to increase the luminance contrast or the letter size could be increased. The letter size was increased to 40 pixels, as this could be done without fear of reducing the bias toward the magnocellular visual pathway, as increasing the luminance contrast to more than 6.9% was more likely to reduce the desired pathway bias.
In the non-masking practice task, participants were asked to identify letters in the parvocellular VBM task and locate the letters briefly presented on the screen under the same stimulus conditions as those to be used in the final VBM task. That
Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia 135
is, red letters of 30 pixels on a green iso-luminant background for the parvocellular non-VBM task, and darker grey letters of 40 pixels presented on a lighter grey background in for the magnocellular non-VBM task. Each letter was presented on the screen for 10 msec. An 85% accuracy score was required for the participant to be considered sufficiently reliable and having adequate visual sensitivity to complete the VBM task.
4.4 Experiment 2: Comparing Visual Backward Masking and Binocular Rivalry
Tasks to Investigate Magnocellular and Parvocellular Processes.
The aim of Experiment 2 was to compare task performance of participants with schizophrenia and controls on the magnocellular and parvocellular BR tasks (using the same stimuli and binocular rivalry method as in Experiment 1) with the magnocellular and parvocellular VBM tasks (as described in Section 4.3.1.2).
4.4.1 Methods.
4.4.1.1 Schizophrenia participants.
Of the 17 participants with schizophrenia that participated in the magnocellular and parvocellular BR tasks, one participant was unable to complete the backward masking task due to an increase in psychotic symptoms associated with their illness, one participant was unable to achieve 85% correct responses in the non-masking task and one participant was unable to identify the letters in the parvocellular VBM task as he was red-green colour blind. This was later confirmed with Ishihara Test for
Colour Blindness (Birch, 1997). This resulted in 14 participants with schizophrenia.
Five participants met the schizophrenia sub-type classification of paranoid schizophrenia with the remaining nine categorised as undifferentiated schizophrenia sub-type. Four participants displayed positive symptoms of schizophrenia, eight negative symptoms and two had equal positive and negative symptoms as assessed
136 Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia
by the PANSS (Kay et al., 1988). Eleven participants were taking atypical anti- psychotic medication (two on Olanzapine, two taking Risperidone, five on Clozapine and one on Quetiapine) and three were taking typical anti-psychotic medication.
Their CPZE dosages ranged from 200-800 mg/day, with the average CPZE being
517.9 mg/day.
4.4.1.2 Healthy controls.
Of the 24 healthy control participants who participated in the magnocellular and parvocellular BR tasks, one participant was not available to complete the second task, and five participants were excluded as they took part in the development of the backward-masking task (this was necessary to eliminate any practice effect); 18 control participants took part in the study. The characteristics of participants are detailed in Table 4.4.
Table 4.4: Age, gender, eye dominance and NART score of controls and participants with schizophrenia.
Controls Schizophrenia χ2 df p (n=18) (n=14) Age Mean (yrs) 36.3 33.9 Range 21-58 23-50 21.029 14 0.278 Gender Male 4 10 Female 14 4 7.748 1 0.011 Eye Dominance R)eye 10 10 L)eye 4 8 0.847 1 0.292 NART Score Mean 116.7 104.5 Range 102-122 101-124 18.194 14 0.198
4.4.2.2 Binocular rivalry and visual backward masking stimuli. The method of collecting binocular rivalry data for this study was undertaken as previously described in Experiment 1 and the VBM task as described in Section
Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia 137
4.3.1.2 (see Appendix 1 and 2 for the written and verbal instructions given to each participant).
4.4.2 Statistical analyses.
Binocular rivalry rate (button pushes per second, Hz), binocular rivalry dominance intervals (the time from onset of perceiving one eye’s image to the onset of the opposing image (measured in msec), and VBM correct scores (number correct total and at each inter-stimulus-interval) were entered into a computerised statistical package (SPSS – Student Version 14) for analysis. Kolmogorov-Smirnov and
Shapiro-Wilks statistics for normality were calculated for both binocular rivalry and
VBM tasks.
Kruksal-Wallis one-way non-parametric ANOVAs were performed to determine the effect that group, gender, age, education and NART score had on binocular rivalry rate in the binocular rivalry tasks and number of correct VBM scores. Planned comparison Mann-Whitney U tests were performed to determine differences in binocular rivalry rate and visual backward masking scores between participants with schizophrenia and healthy controls in both the magnocellular and parvocellular tasks. Plotted normalised dominance intervals for the BR tasks were compared using a one-way Smirnov test.
4.4.3 Results.
4.4.3.1 Binocular rivalry rates.
As the binocular rivalry rate data were not normally distributed, Kruksal-
Wallis one-way non-parametric ANOVAs were performed. It was revealed that group had a significant main effect on binocular rivalry rate for both the magnocellular and parvocellular BR tasks; χ2 (1, 41) = 5.374, p<.02 magnocellular
BR task and χ2 (1, 41) = 7.498, p<.006 in the parvocellular BR task. Age and gender
138 Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia
had no effect on binocular rivalry rate in either task (age χ2 [18, 41] = 15.210, p=
.648 and χ2 [18, 41] = 19.656, p= .353; gender χ2 [1, 41] = 1.977, p =. 16 and χ2 [18,
41] = 0.925, p = .335 for magnocellular BR task and parvocellular BR tasks, respectively). The gender effect reported in Experiment 1 was not replicated here.
Six female healthy control participants and three male participants with schizophrenia were excluded from participating in the second experiment, which was likely to account for this.
Participants with schizophrenia recorded significantly slower binocular rivalry rates in both the magnocellular and the parvocellular BR tasks compared to controls
(see Figure 4.3). Mean binocular rivalry rate for the magnocellular task in the group with schizophrenia was 0.24 Hz (SD = 0.12) compared with 0.39 Hz (SD = 0.16) in healthy controls (Mann-Whitney U test, Z = -2.318, p < .02). In the parvocellular BR task, the mean binocular rivalry rate in the schizophrenia group was 0.24 Hz (SD =
0.09), compared to 0.44 Hz (SD = 0.24) in healthy controls (Mann-Whitney U test, Z
= -2.738, p < .005).
A significant difference in binocular rivalry rates for the magnocellular and parvocellular tasks was found in healthy participants (magnocellular mean rate 0.39
Hz, SD = 0.156, versus parvocellular 0.44Hz, SD = 0.24, Z = -1.47, p= .047).
Participants with schizophrenia showed no difference in binocular rivalry rates between the magnocellular and parvocellular BR tasks (mean rate 0.24 Hz, S =. 0.09 and mean rate 0.22 Hz, SD = 0.11 respectively, Z = -0.621, p= .535).
Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia 139
0.6
0.5 0.44 Key 0.4 0.39 Control (n=18) 0.3 Schizophrenia (n=14) BR rate rate in Hz BR 0.24 0.24 0.2 (button pushes/second) (button 0.1
0 Magnocellular BR Task Parvocellular BR Task
Figure 4.3: Mean binocular rivalry (BR) rates recorded in participants with schizophrenia (black triangles) compared to healthy controls (black diamonds).
Note: Error bars show standard errors of the mean.
Diagnostic sub-group, medication dose and negative and positive symptoms of schizophrenia had no effect on binocular rivalry rate for either the magnocellular or parvocellular tasks (Mann-Whitney U tests): diagnostic subgroup (paranoid schizophrenia [n = 5] versus undifferentiated schizophrenia [n = 9] magnocellular
BR task Z = -0.468, p= .699) and parvocellular BR task [Z = -1.470, p= .147]; low-
[<425 mg, n = 4] versus high-dose [>425 mg, n = 8] of anti-psychotic medication magnocellular BR task [Z = -0.142, p = .945] and parvocellular BR task [Z = -0.354, p = 9.733] and positive symptom [n = 4] versus negative symptom [n = 8] schizophrenia magnocellular BR task [Z = -0.595, p= .507] and parvocellular BR task [Z = -0.766, p = .461]). Two participants had equal positive and negative symptom scores, and were excluded from the analyses.
4.4.3.2 Dominance intervals.
One-way Smirnov tests revealed significant differences in the distribution of normalised dominance intervals in participants with schizophrenia compared with healthy controls in both the magnocellular and the parvocellular BR tasks.
140 Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia
Significant differences in the distributions of dominance intervals occurred in both the magnocellular and parvocellular BR tasks at the p < .05 level of significance (as
T1>CV-ST). See Table 4.5.
Table 4.5: Differences in the distribution of dominance durations between participants with schizophrenia and controls in magnocellular and parvocellular binocular rivalry (BR) tasks: Smirnov test outcomes of dominance duration distributions.
Schizophrenia Healthy Critical Value Smirnov Reject Ho? Participants Controls -Smirnov Test T Reject if m n 1.36√ m+n/ T1>CV-ST mn (T1) Magnocellular 1332 2592 0.045849 0.08552 Yes BR Task Parvocellular 1314 2991 0.045011 0.07690 Yes BR task
The greatest differences in distribution functions in both magnocellular and parvocellular BR tasks occurred at the 0.5 second time interval (see Figure 4.2).
Thus participants with schizophrenia recorded significantly more dominance intervals of 0.5 seconds duration than healthy controls. Although participants with schizophrenia recorded more dominance durations of less than one second in the magnocellular BR task, they generally recorded few dominance durations from 1.5 to
5 seconds compared to control participants, resulting again in a slightly flatter distribution (Figure 4.4a).
4.4.3.3 Visual backward masking (VBM).
Kruksal-Wallis one-way non-parametric ANOVAs were performed on the correct scores for both VBM tasks. Group had a significant main effect on VBM scores in both the magnocellular and parvocellular VBM tasks (magnocellular VBM task: group χ2 [18, 41] = 6.677, p= .01; parvocellular VBM task: χ2 [18, 41] =
10.345, p < 0.001). Age and gender had no effect on binocular rate for either task
(Kruksal-Wallis χ2, p>0.05). Thus, participants with schizophrenia identified the
Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia 141
location of the target in the magnocellular VBM and the identity of the target in the parvocellular VBM task less frequently than controls at all inter-stimulus intervals
(however these differences only reached statistical significance [Mann-Whitney U test] for inter-stimulus intervals of 27, 53 and 107 msecs in the parvocellular VBM task). See Table 4.6 for results.
Table 4.6: Differences in correct identification of a target scores in magnocellular and parvocellular visual backward- masking (VBM) tasks between participants with schizophrenia and healthy controls at four inter-stimulus intervals (ISI)
Magnocellular VBM Task Controls Schizophrenia (n = 18) (n = 14) M SD M SD U Z p ISI 27msec 7.4 3.2 7.5 3.4 125.5 -0.190 .985 ISI 53msec 10.0 3.9 8.5 3.8 100.5 -0.973 .330 ISI 107msec 11.3 4.0 9.1 3.9 85.0 -1.565 .118 ISI 213msec 11.8 3.9 10.6 5.3 114.0 -0.460 .646 Parvocellular VBM Task Controls Schizophrenia (n = 18) (n = 14) M SD M SD U Z p ISI 27msec 9.7 2.3 7.4 2.7 64.0 -2.376 .018* ISI 53msec 11.6 2.3 8.6 3.3 61.0 -2.499 .012* ISI 107msec 12.7 2.8 9.9 4.3 70.0 -2.138 .032* ISI 213msec 12.5 2.4 12.2 3.6 122.0 -0.153 .878 ISI 27msec 9.7 2.3 7.4 2.7 64.0 -2.376 .018* Note: * indicates p < .05 significance
Mann Whitney U tests revealed no significant effect of medication dose or positive and negative symptom ratings in either the magnocellular or parvocellularVBM task (p < .05). However, a significant effect of schizophrenia sub-type (un-differentiated or paranoid schizophrenia) was found in the magnocellular VBM task at inter-stimulus intervals of 27 msec and 53 msec (Z = -
2.665, p = .007, and Z = -2.094, p = .042 respectively), with no effect observed in the parvocellular VBM task at these inter-stimulus intervals.
Dose level had a significant effect on VBM score for inter-stimulus intervals of
27 msec in the magnocellular VBM task (Z = -2.030, p= .042) and DSM-IV
142 Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia
diagnostic sub-group had a significant effect on VBM score for inter-stimulus intervals of 27 msec and 53 msec in the magnocellular VBM task (Z = -2.665, p =
.008 and Z = -2.094, p= .036 respectively). However, DSM-IV diagnostic sub-group
(paranoid schizophrenia versus undifferentiated schizophrenia as per DSM-IV classification) and medication dose had no effect on the remaining VBM scores.
Negative and positive symptoms of schizophrenia had no effect on VBM scores in the remaining inter-stimulus intervals in the magnocellular VBM task or at any inter- stimulus intervals in the parvocellular VBM task for participants with schizophrenia
(Mann-Whitney U tests) (See Table 4.5, Appendix C).
a.
1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3
Cumulative Probability 0.2 0.1 0.0 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6 6.5 7 7.5 8 8.5 9 Time in Seconds b. schizophrenia Control
1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3
Cumulative Probability Cumulative 0.2 0.1 0.0 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6 6.5 7 7.5 8 8.5 9 Time in Seconds
Schizophrenia Control
Figure 4.4: The dominance durations between participants with schizophrenia (n=14; black lines) compared to control participants (n=18; grey lines) for (A) magnocellular binocular rivalry (BR) task and (b) parvocellular BR task.
Note: A separation in location of any two time points on each curve indicates a significant difference in mean normalised dominance durations.
Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia 143
Mean correct responses were plotted against inter-stimulus interval for each task and these masking functions are presented in Figure 4.5.
16
14 12 10 8 6 Correct Responses 4 2 0 1 23 45 67 89 111 133 155 177 199 221 243 Inter-stimulus Intervals in msec a.
Control (n=18) Schizophrenia (n=14)
16 14 12 10 8 6 Correct Responses 4 2 0 1 23 45 67 89 111 133 155 177 199 221 243 Inter-stimulus Intervals in msec b.
Figure 4.5: Number of correct responses as a function of inter-stimulus interval in controls and participants with schizophrenia for (a) magnocellular visual backward- masking(VBM) and (b) parvocellular VBM tasks.
Note: Error bars show standard error.
144 Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia
4.4.3.4 Comparing binocular rivalry and visual backward masking results.
To be confident in the binocular rivalry data presented in Experiments 1 and 2 and validating the use of pathway-biased stimuli in binocular rivalry, it would be expected that magnocellular binocular rivalry and VBM, and parvocellular binocular rivalry and VBM tasks would be significantly associated. Correlation coefficients are presented in Table 4.7.
When VBM correct scores were compared with the binocular rivalry rates (in
Hz) it can be seen that participants with schizophrenia performed more poorly in both magnocellular and parvocellular tasks compared to the control participants, with the greatest differences recorded in the parvocellular tasks. Correlations between correct VBM scores and binocular rivalry rates were examined. Significant correlations were evident between parvocellular binocular rivalry rates in parvocellular VBM task scores at inter-stimulus intervals of 27, 53, 107 and 213 msec and between magnocellular binocular rivalry rates and parvocellular visual backward masking task scores at inter-stimulus intervals of 53, 107 and 213 msec in healthy control participants. Thus control participants with slower binocular rivalry rates, in both magnocellular and parvocellular BR tasks, performed more poorly on parvocellular VBM tasks than participants with faster binocular rivalry rates.
Participants with schizophrenia did not show any significant correlations between binocular rivalry rates and visual backward masking scores in either parvocellular or magnocellular tasks (with the exception of a near significant correlation of p= .053 at inter-stimulus interval 53 msec in parvocellular binocular rivalry and VBM tasks).
Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia 145
Table 4.7: Correlations between magnocellular and parvocellular binocular rivalry (BR) rates (in Hz) with magnocellular and parvocellular visual backward masking (VBM) correct scores (Spearman’s correlation coefficient rho).
Controls (n=18) Magnocellular BR task Parvocellular BR task (rate in Hz) (rate in Hz) r2 p r2 p Magnocellular VBM Task (correct scores) ISI 27msec 0.205 .414 0.301 .224 ISI 53msec 0.104 .680 0.269 .281 ISI 107msec 0.142 .575 0.283 .256 ISI 213msec 0.147 .560 0.066 .795 Parvocellular VBM task (correct scores) ISI 27msec 0.353 .151 0.474 .047* ISI 53msec 0.518 .028* 0.581 .011* ISI 107msec 0.501 .034* 0.484 .042* ISI 213msec 0.655 .003* 0.587 .010*
Schizophrenia (n=14) Magnocellular BR task Parvocellular BR task (rate in Hz) (rate in Hz) r2 p r2 p Magnocellular VBM Task (correct scores) ISI 27msec 0.016 .957 0.248 .392 ISI 53msec -0.039 .895 0.025 .934 ISI 107msec -0.243 .403 -0.208 .477 ISI 213msec -0.235 .418 -0.089 .763 Parvocellular VBM task (correct scores) ISI 27msec -0.161 .583 -0.443 .113 ISI 53msec -0.333 .244 -0.526 .053* ISI 107msec -0.226 .436 0.020 .946 ISI 213msec -0.129 .661 -0.154 .598 Note. * indicates p < .05 significance (two tailed).
With respect to the magnocellular VBM and binocular rivalry tasks, no correlations were evident in either healthy control participants or participants with schizophrenia when the magnocellular VBM task was compared with magnocellular and parvocellular BR tasks. It is also possible that methodological differences
146 Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia
between the tasks reduced correlations in the magnocellular tasks. For example, equal strength mask and stimuli were used in this study in the magnocellular VBM
(as previously discussed), and moving stimuli at low spatial frequency were used in the binocular rivalry task compared with stationary peripherally-located targets and mask in the VBM (chromaticity and luminance contrast were relatively matched between the tasks). An alternative interpretation of these data is that only the parvocellular pathway contributes to binocular rivalry, or that binocular rivalry rate reflects only the activity of the parvocellular visual pathway.
4.4.4 Discussion relating to visual backward masking.
Slower binocular rivalry rates were recorded in participants with schizophrenia compared with controls (see Figure 4.3), with the greatest difference being recorded in the parvocellular BR task, replicating the results found in Experiment 1. No significant differences in binocular rivalry rates were recorded in participants with schizophrenia between the magnocellular and parvocellular BR tasks (Z = -0.621, p=
.535), while control participants recorded significantly faster binocular rivalry rates in the parvocellular BR than the magnocellular BR task (Z = -1.47, p= .047).
Significant differences were found in the distribution of dominance durations between participants with schizophrenia and controls in both binocular rivalry conditions. Participants with schizophrenia recorded more dominance intervals of less than one second than controls and fewer dominance durations of 1.5 to 5 seconds duration. This was particularly evident in the magnocellular BR task on visual inspection of the dominance duration functions. Slower binocular rivalry rates in the group with schizophrenia taken together with a significant difference in the distribution of dominance durations, is suggestive of an abnormality in one of both of the visual pathways in schizophrenia. These data do not allow conclusions to be
Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia 147
drawn as to which pathway, or whether both pathways are contributing to abnormal binocular rivalry rates and dominance distributions in schizophrenia. A plausible explanation is that over-active magnocellular neurons distributed across the retina send rapid transient responses to visual stimuli during binocular rivalry (as evidenced by the increased number of short dominance durations), interrupting the sustained response of the parvocellular neural processing (Butler et al., 2003).
In participants with schizophrenia, increased numbers of short dominance durations do not correspond with faster binocular rivalry rates, thus an overall slower rate must be accounted for by some abnormally long dominance durations (more 1.5-
5 second dominance durations were recorded in the schizophrenia group). Slower binocular rivalry rates in participants with schizophrenia may reflect more “sluggish” or prolonged processing by parvocellular neurons in schizophrenia. The data presented here are suggestive of abnormalities in both the magnocellular and parvocellular pathways. Further investigation is needed to determine whether abnormalities is the two pathways is responsible for the atypical dominance durations and slower binocular rivalry rates in schizophrenia.
Participants with schizophrenia performed more poorly on VBM tasks than healthy participants, consistent with previous reports (Braff, Saccuzzo & Geyer,
1991; Green et al., 2003; Green et al., 1994b; Koelkebeck et al., 2005). Participants with schizophrenia generally identified the location of the target in the magnocellular
VBM task and the identity of the target in the parvocellular VBM task less frequently than healthy participant’s at all inter-stimulus intervals. Overall group differences in correct scores were observed in both the magnocellular and parvocellular VBM tasks; however the greatest difference in mean scores was recorded in the parvocellular VBM task (2.3 at inter-stimulus of 27 msec, 3 at 53
148 Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia
msec, and 2.6 at 107 msec). Statistical significant for inter-stimulus intervals of 27 msec (p= .018), 53 msec (p = .012) and 107 msecs (p= .032) in the parvocellular
VBM task (Table 4.4). The lack of effect in the magnocellular task may be due narrow range of ISI’s selected for this task. It is likely that greater difference in the magnocellular task would have been observed between participants with schizophrenia and controls at ISI’s of greater than 400 – 800 msec. Longer ISI’s are necessary for individuals with schizophrenia to escape the masking effects in VBM tasks (Schechter, et al., 2003). Future studies that incorporate VBM tasks biased to include a greater range of ISI’s are needed.
Abnormalities in VBM in schizophrenia have typically been attributed to magnocellular rather than parvocellular pathway processing (Cadenhead et al., 1998;
Green et al., 1994b, Koelkebeck et al., 2005; Schechter et al., 2003). Methodological differences may account for the different results reported here. To bias the magnocellular visual pathways, researchers have typically developed VBM tasks where the mask is of greater energy than the target. By increasing the presentation duration time (Cadenhead et al., 1998; Green et al., 2003), luminance contrast
(Schechter, et al., 2003) and spatial frequency (Butler, 2003; Butler et al., 2005;
Slaghuis & Curran, 1999) the mask is presented at greater energy than the target.
This is based on the observation that the contrast range over which transient
(magnocellular) neurons responds dynamically (give an increase in response to an increase in stimulation) is smaller than that of sustained (parvocellular) neurons, and that transient neurons saturate sooner than sustained neurons (Breitmeyer & Ganz,
1976). Thus, if a mask is presented at greater duration, at greater luminance contrast or spatial frequency to the target, the mask is considered to stimulate sustained rather than transient pathway processing, with the brief duration of the preceding target
Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia 149
stimulating transient pathway processing. Because the primary interest in this experiment was to develop a task that preferentially biased the transient and sustained pathways to compare with a binocular rivalry task, the mask and targets were of the same energy in terms of stimulus duration, luminance contrast and spatial frequency to match the stimulus characteristics of the binocular rivalry tasks.
The binocular rivalry stimuli only differed in terms of line orientation (vertical versus horizontal lines).
The lack of a medication effect on VBM performance observed here is consistent with other studies (Butler et al., 2003, Braff & Saccuzzo, 1992;
Cadenhead et al., 1998). However, the absence of a finding related to positive and negative symptoms of schizophrenia has not been reported previously, where VBM information processing deficits have been consistently reported in groups with more negative rather than positive or disorganised symptoms of schizophrenia (Butler et al., 2003; Cadenhead et al., 1997; Schechter et al., 2003; Slaghuis & Bakker, 1995;
Slaghuis & Curran, 1999). This may be due to the small sample size (four participants with positive symptoms compared to eight with negative symptoms) and the fact that this sample comprised a group of out-patient participants who did not have acute symptoms of illness at the time of testing.
4.5 General Discussion
The key to the sustained versus transient (or magnocellular versus parvocellular) explanations of visual masking is the difference in transmission time from the retina to the cortex of the two pathways (May, Grannis & Dunlap, 1988).
Breitmeyer and Ganz (1976) demonstrated that transient (magnocellular) channel neurons respond to the onset and offset of a stimulus 50-80 msecs before the sustained (parvocellular) channel neuron, with the response of the sustained channel
150 Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia
neuron dependent on the spatial frequency of the stimulus (although Laycock et al.,
(2008) suggests that the magnocellular advantage in humans is approximately 25 –
30 msecs). A stimulus of high spatial frequency has a long latency in response and lower response amplitude than one of lower spatial frequency. Breitmeyer and Ganz
(1976) explain the time course difference in responses of transient and sustained neurons in the retina, LGN and primary visual cortex in the following diagram.
Figure 4.6 demonstrates the time course differences between transient and sustained responses to a brief presentation of a stimulus.
Figure 4.6: The hypothesised time course of activation of transient and sustained channels after a brief presentation of a stimulus.
Note: In the sustained channels, the solid line indicates activity of the intermediate spatial frequency channels, the dashed line high spatial frequency channels and the dotted line very high spatial frequency channels.
In VBM tasks Breitmeyer & Ganz (1976) suggest that the time difference in response of the transient and sustained neurons in the retina and LGN account for the masking effects seen in VBM tasks. They suggest that transient neurons react rapidly to the onset of the target stimulus, to locate the stimulus and stimulate eye movements to secure the target in the visual scene. The slower responding sustained
Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia 151
neurons then processes the spatial and colour features of the stimulus to identify the stimulus. If a mask is presented a short time after the target the response from the transient channels may inhibit (or interrupt) the processing of the sustained channel, or if the sustained channel has partially responded, integrate with the response.
These authors presented a model of visual masking outlined in Figure 4.7.
T Target S
- + Mask
0 100 200 300 400 msec
Adapted from Breitmeyer, B. G. and L. Ganz (1976). "Implications of sustained and transient channels for theories of visual pattern masking, saccadic suppression, and information processing." Psychological Review 83(1): 1-36.
Figure 4.7: The time course of the transient and sustained channels when the target precedes the mask (backward masking).
T = transient channel, S = sustained channels. Arrows indicate the direction of the masking interaction. A minus sign indicates that the interaction is inhibitory, and a positive sign indicates that the interaction is one of sensory integration.
Contemporary schizophrenia researchers typically subscribe to one of two interpretations of the visual abnormalities attributed to transient channel or magnocellular pathway from this model. One suggests that the transient channel is over-active in schizophrenia and interrupts the processing of the parvocellular pathways, while the other suggests that the over-active transient channel affects the integration of images into stable precepts. Interruption has been demonstrated in
152 Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia
VBM tasks where the sustained channel sensitive to stimuli that is moderate-to-high spatial frequency and slow temporal frequency codes fine detail necessary for object recognition (the target) is interrupted by faster responding transient channel activity elicited by the mask (Cadenhead et al., 1998; Green et al., 1994a; Green et al.,
1994b; Rassovsky, Green, Nuechterlein, Breitmeyer & Mintz, 2004). This theory has been put forward to describe the visual and auditory hallucinations that are commonly seen in schizophrenia. The second theory suggests that the transient pathway is defective in schizophrenia, needing abnormally long periods of time between the presentation of images in order to recognise and code them. When images are seen in quick succession (with short inter-stimulus intervals) the information from both images is integrated or fused. Individuals with schizophrenia may therefore be creating ‘false’ or ‘incorrect’ visual images and be mis-interpreting visual information contributing to the paranoia and perceptual disturbances commonly experienced in this illness. Impairments in visual integration have been linked to increases in disorganised symptoms (Butler, Silverstein & Dakin, 2008;
Uhlhaas, Phillips & Siverstein, 2005; Uhlhaas, Phillips, Mitchell & Silverstein,
2006), poorer pre-morbid social functioning (Chen, Nakayama et al., 2003) and increased illness severity and chronicity (Silverstein et al., 2006). Deficits in integration have also been reported in first-episode participants (Javitt, 2009;
Uhlhaas et al., 2006) and deficits in the magnocellular system correlate significantly with global outcome and level of community functioning (Schechter et al., 2005).
Although it remains unresolved whether the VBM dysfunction in schizophrenia reflects the abnormality of sub-cortical transient channels or deficient cortical mechanisms (Keri et al., 2000), data from fMRI studies show that participants with schizophrenia have markedly lower activation to low spatial
Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia 153
frequency stimuli in regions of the occipital, parietal and temporal lobes (Martinez et al., 2008), suggesting cortical regions are involved, especially when the LGN is functioning normally. It is possible that the initial abnormality may occur earlier in the pathway. Deficits in early-stage visual processing predict higher cognitive deficits in schizophrenia (Butler et al., 2005) and may contribute to higher-order cognitive deficits in working memory, executive functioning and attention (Martinez et al., 2008).
4.5.1 A model of binocular rivalry based on visual backward masking theory.
According to the sustained-transient theory in VBM, if the mask and test stimuli are similar in orientation and spatial frequency, maximum masking will occur at stimulus onset synchrony. This prediction stems from the assumption that when the mask and target are similar, equal proportions of magnocellular and parvocellular cells are stimulated and masking effects derive from ‘within channel’ inhibition
(transient on transient and sustained on sustained) (May et al., 1988). Breitmeyer and Ganz (1976) postulated that transient neurons inhibited sustained ones via internuncial neurons at the LGN and cortex based on their response duration. See
Figure 4.8.
It is conceivable that binocular rivalry processing may occur in a similar way.
Visual information from the left and right eyes travels via monocular neurons and binocular neurons to the LGN and to the left and right visual cortex. Visual information is carried more rapidly to the cortex by monocular than binocular neurons, and both types contain magnocellular and parvocellular cells, with parvocellular neurons concentrated around the fovea while the density of magnocellular neurons increases with foveal eccentricity (Livingstone & Hubel,
1987).
154 Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia
Target
Sustained Sustained
Mask Internuncial Internuncial
Transient Transient Retina LGN Cortex
Adapted from Breitmeyer, B. G. and L. Ganz (1976). "Implications of sustained and transient channels for theories of visual pattern masking, saccadic suppression, and information processing." Psychological Review 83(1): 1-36.
Figure 4.8: Transient (magnocellular) neurons inhibit sustained ones via internuncial neurons at the lateral geniculate nucleus (LGN) and cortex. The impulse response by the internuncial neuron is inhibitory at the postsynaptic potential and integrates with the sustained neuron at either the LGN or cortex.
‘Inter-ocular grouping’ occurs during rivalry, where many small targets
scattered through the visual field can engage in synchronised alternation (Alais &
Blake, 1999). When patchwork rival figures are presented to each eye (for example,
grating patches of different orientation, or composite images of a monkey face and
text), observers are able to see two globally coherent figures (Kovacs et al., 1996;
Blake, 2001), indicating that rivalling zones are not independent and they may be
grouped by lateral connections between cortical hypercolumns (Alais & Blake,
1999).
When stimuli are continuous the image fades as the neurons in the visual
pathways saturate; this is known as Troxler effect (Levelt, 1968) or ‘Troxler fading’.
Troxler fading can either be disrupted by large voluntary or slight involuntary eye
movements or micro saccades (Martinez-Conde et al., 2006). Micro saccades cause
the eyes to shift slightly across the visual field, so that an image is never entirely
stable on the retina for any appreciable time. Burr, Ross and Murrone (1994)
Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia 155
suggest that during these micro saccades saccadic suppression occurs to create a stable continuous image so that humans perceive a single stable image. They suggest that this suppression is selective for patterns modulated in luminance at low spatial frequencies (magnocellular or transient pathways). Patterns of higher spatial frequency and equiluminant patterns (those stimulating parvocellular or sustained pathways) are not suppressed during saccades, but enhanced, setting up a situation of magnocellular suppression and parvocellular dominance in early in visual processing, possibly as early as the lateral geniculate nucleus. The disruption from micro saccades interrupts the Troxler fading (Martinez-Conde et al., 2006) and triggers dominance changes during binocular rivalry (Blake et al., 1990, 2003; Carter and Cavanagh, 2007; Alais et al., 2010).
This model suggests that the magnocellular pathway gates, (Javitt, Liederman,
Cienfuegos & Shelley, 1999) or acts as a ‘switch’, with its rapid response to local visual information turning off or interrupting cortical processing the parvocellular neurons in the cortex derived from parvocellular neurons located in corresponding retinal location in the opposite eye. The magnocellular neurons saturate quickly, before the slower parvocellular neuron responds, allowing the observer to ‘see’ the image being processed by the parvocellular pathway. This activity occurs over the entire retinotopic area with small patches of activity denoting each hypercolumn, which are connected together by lateral connections (Alais & Blake, 1999).
This revised model combines two prevailing models of binocular rivalry; that of pattern rivalry (where the conflicting stimuli presented to each eye compete for dominance from interactions between monocular and binocular neurons in the visual cortex, see (Blake, 2001) and the pathway model of binocular rivalry that suggests that binocular rivalry is related to the actions of the parvocellular, magnocellular
156 Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia
pathway processing, or both in the retina, LGN and cortex (Blake, 1991; He et al.,
2005).
In Experiments 1 and 2 control participants recorded significantly faster binocular rivalry rates using stimuli biased to the parvocellular pathway compared to a binocular rivalry task biased to the magnocellular pathway. This revised model predicts that in the parvocellular binocular rivalry condition, where the parvocellular visual pathway response is stronger than the magnocellular response, the image is able to be identified based on its colour and spatial information before the magnocellular response from the opposite eye interrupts processing; thus allowing crisp alternation between the left and right eye’s visual images. In the magnocellular-biased condition the magnocellular response is stronger so the interruption of the response from the opposing eye occurs quickly after the saturation of the first eye’s response so processing of the response of the parvocellular neurons occur after the saturation of the magnocellular neurons of both eyes, slowing down the binocular rivalry alternation rate.
No significant differences were found between rates in binocular rivalry tasks that biased the magnocellular and parvocellular pathways in participants with schizophrenia. It has been postulated that abnormal magnocellular pathways in participants with schizophrenia interrupt or abnormally integrate with the processing of parvocellular pathways (Green et al., 1994b; Green et al., 1994a; Green et al.,
2009; Keri et al., 2004). Over-active magnocellular pathways in the model would lead to a rapid response and saturation of magnocellular neurons which interrupt the parvocellular pathways’ response to the finer details of the image and the perception of the opposing image. This would shorten the dominance duration.
Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia 157
Figure 4.9: A revised model of binocular rivalry with rapid magnocellular response followed by the parvocellular response to continuous stimuli (vertical and horizontal lines) in the right and left eyes respectively at corresponding retinotopic areas.
Note: Arrows indicate if the masking interaction is interruption or integration. The bottom axis denotes the fluctuating images seen during binocular rivalry over time. Note that the duration of the image is not constant.
If the magnocellular neurons response by the opposite eye occurs as the parvocellular neurons saturate no interruption would occur, with integration lengthening the dominance duration thus slowing the rate. An interpretation of this would be that the magnocellular pathway is responsible for triggering the alternation of images seen in binocular rivalry by the action of the magnocellular afferent neurons in the LGN inhibiting parvocellular neurons in the cortex. It may be the action response of the parvocellular neurons in the cortex that determine the duration of the dominance duration of the image, and thus the rate. If the magnocellular pathway is overactive, cortical activity of the parvocellular pathway is disrupted, thus binocular rivalry rate slows. The higher number of shorter dominance durations recorded by participants with schizophrenia may reflect early magnocellular processing, while the abnormally long dominance durations seen in participants with
158 Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia
schizophrenia (and not healthy participants) may reflect abnormal parvocellular processing at the cortical level.
A limitation of the binocular rivalry task is that it relies on self-report reporting of perceptual alternation is effected by reaction time. It is not possible to be sure that the participant is accurately report what they perceive. Participants that experience quicker perceptual alternations during binocular rivalry may not have sufficient time to respond pressing a response key before the opposing image becomes dominant. In humans recognition of an object generally occurs prior 180 msec with a motor response intiated from 540-720 msec (Castelo-Branco, Neuenschwande & Singer,
1998). If a change in perceptual dominance occurs around 500 msec, it is possible that an individual with schizophrenia may not be able to register their perception of the image before the next alternation occurs. Measuring participant’s reaction times in future studies to ensure no confound related to reaction time (slower in schizophrenia) would be a useful methodological advance (Ngan & Liddle, 2000).
Furthermore, Braff and Saccuzzo (1985) note that information-processing deficits in individuals with schizophrenia occur at ISI’s between 60 msec and 500 msec in VBM tasks. Future VBM studies that include longer ISIs between target and mask, that reflect the temporal characteristics of perceptual alternations or dominance durations in binocular rivalry, may allow greater exploration of magnocellular and parvocellular processing in schizophrenia. VBM tasks that include greater ISI’s (of 400 – 800 msec) may revealed greater seperation between participants with schizophrenia and controls.
4.6 Conclusion
Participants with schizophrenia recorded slower binocular rivalry rates than healthy controls in two binocular rivalry tasks that were biased to processing via the
Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia 159
magnocellular and parvocellular pathways, with the greatest difference in binocular rivalry rates being observed in the parvocellular binocular rivalry task. Two backward-masking tasks were developed; a location task to access magnocellular processing, and an identification task to access parvocellular processing, to compare performance with the binocular rivalry tasks. Participants with schizophrenia performed more poorly in both the magnocellular and parvocellular backward masking conditions, with the greatest difference being in the parvocellular backward- masking task.
A revised model of binocular rivalry that combines pattern rivalry theory with a pathway theory was proposed to explain the results. However further investigation into this model of binocular rivalry are needed. Future studies that include binocular rivalry tasks that are biased toward the magnocellular and parvocellular visual pathways compared VBM studies that include longer ISIs between target and mask
(400-1200msec), that reflect the temporal characteristics of perceptual alternations or dominance durations in binocular rivalry, may allow greater exploration of magnocellular and parvocellular processing in schizophrenia.
160 Chapter 4: Binocular Rivalry and Backward-Masking Tasks Reveal Pathway-Specific Abnormalities in Schizophrenia
Chapter 5: Benton’s Judgment of Line Orientation - An Indicator of Visuospatial
Ability in Schizophrenia
5.1 The Right Hemisphere and Visuospatial Dysfunction
Pettigrew and Miller (1998) and Miller et al., (2003) suggested that binocular rivalry is the result of competition between the two cortical hemispheres that occurs by virtue of an ‘inter-hemispheric switching’ mechanism (see Chapter 3 for further discussion). This theory assumes that visual information originating from both eyes combines to form a stable percept within each hemisphere that competes for dominance over the other. Thus, if visual processing within one hemisphere was abnormal (or one hemisphere was damaged) binocular rivalry processing would be impaired. Right hemisphere processing abnormalities have been observed in individuals with schizophrenia during neuro-psychological testing, such as a lateralised lexical decision task (Endrass et al., 2002; Evans & Schwartz, 1997;
Gastaldo et al., 2002; Lieb et al., 1996; O’Donnell et al., 2002) a two-pulse temporal discrimination task (Schwartz, et al., 1984) backward masking tasks (Lieb et al.,
1996; Wynn, Light, Breitmeyer, Nuechterlein & Green, 2005). To determine whether the slow binocular rivalry rates observed in individuals with schizophrenia
(see Chapters 3 and 4) can be attributed to dysfunction in the cortical hemispheres, results for binocular rivalry were compared to task performance on the Benton’s
Judgment of Line Orientation (BJLO) task (Benton et al., 1978); the BJLO task is widely accepted to be processed within the right cortical hemisphere.
The BJLO task (Benton et al., 1978) has most frequently been used to test the presence of visuospatial abnormalities and right hemisphere dysfunction (Benton,
Hannay & Varney, 1975; Benton et al., 1978, Hamsher, Capruso & Benton, 1992;
Hannay, Varney & Benton, 1976; Treccani, Torri & Cubelli, 2005; Trahan, 1998).
Chapter 5: Benton’s Judgment of Line Orientation - An Indicator of Visuospatial Ability in Schizophrenia 161
Benton, Hannay and Varney (1975) observed that right-handed, right-brain-damaged individuals were poorer at line orientation tasks compared to their healthy counterparts, with left-brain-damaged individuals performing no differently to healthy controls. These data have been replicated in a number of studies and are supported by neurophysiological studies in both brain-diseased and healthy adults
(Hamsher et al., 1992; Isaacs, Edmonds, Chong, Lucas & Gadian, 2003; Finton,
Lucas, Graff-Radford & Uitti, 1998; Ng et al., 2001). Imaging studies (fMRI) reveal that performing judgments of line orientation activate the right ventral extrastriate cortex (Deutsch, Bourbon, Papanicolaou & Eisenberg, 1988; Hamsher et al., 1992;
Hannay et al., 1976; Isaacs et al., 2003; Ng et al., 2001; Tranel, Vianna, Manzel,
Damasio & Graowski, 2009) and increased blood flow in the right tempro-occipital region has been observed using blood-oxygen-level dependent BOLD fMRI
(Deutsch et al., 1988; Hannay et al., 1976; Finton et al., 1998). In contrast, one fMRI study reported robust bilateral cortical activation of equal strength in both right and left superior parietal lobes, suggesting that both hemispheres were involved
(Nurnberger et al., 2000). This was corroborated by lesion data. However, when these authors analysed wavelet data they observed an earlier and stronger high- frequency signal over the right parietal lobe (four times stronger than those recorded from the left), suggesting the right lobe has a ‘priming’ effect in visuospatial processing. More recently, Tranel et al., (2009) found defective performance on the
BJLO task to be associated with damage to the right posterior parietal region
(specifically, in the angular gyrus and posterior supramarginal gyrus) and occipitoparietal region (specifically, extending into the lateral superior occipital gyri). These findings, using detailed modern lesion analysis techniques, are consistent with the traditional proposed hemispheric underpinning of the BJLO (e.g.
162 Chapter 5: Benton’s Judgment of Line Orientation - An Indicator of Visuospatial Ability in Schizophrenia
Benton et al., 1994). Cortical processing observed by fMRI during the BJLO tends is hypothesised to reflect ‘dorsal stream’ processing systems, occurring within the posterior sector of the supramarginal gyrus, generally related to spatial functions.
Tranel et al., (2009) suggests the BJLO task is thus as an ‘occipitoparietal’ test, consistent with the dorsal ‘where’ visual processing stream. In summary, the BJLO provides an indication of right hemisphere cortical processing and is a relatively pure visuospatial task. A large body of evidence supports the right hemisphere being the
‘dominant’ or ‘preferred’ system for processing visuospatial information (Tranel et al., 2009). It is noteworthy that no parietal activation was observed (with fMRI) in a non-spatial visual perception task; the Facial Recognition Test (Benton & Van Allen,
1968), suggesting parietal lobe activation may be specific to visuospatial processing
(Nurnberger et al., 2000; Tranel,et al., 2009).
In this chapter, two experiments are described. The first being the development of a computer version of the BJLO and data collection tool; the second comparing BJLO performance in a group of individuals with schizophrenia compared to a group of healthy control participants.
5.2 The Benton’s Judgment of Line Orientation Task
As described, the BJLO is a relatively pure visuospatial task. It requires minimal motor involvement and has good validity and reliability (Benton, 1983;
Eden, Stein, Wood & Wood, 1996; Woodard et al., 1996). The BJLO is performed under free-space viewing conditions; it is easily administered and has no time restrictions (Benton, 1978; Benton, 1983). The task has a test retest reliability of r =
0.90 (Benton et al., 1978). Task performance has been associated with gender and age; with performance declining with increasing age and females on average, performing more poorly than males (Benton et al., 1978; Benton, 1983; Benton,
Chapter 5: Benton’s Judgment of Line Orientation - An Indicator of Visuospatial Ability in Schizophrenia 163
1994; Caparelli-Daquer, Oliveira- Souza & Filho, 2009). Population norms and adjustments for group comparisons have been established. See Benton (1983) and
Benton (1994).
The BJLO task comprises 30 different items. Presented in the lower portion of each item is a reference image comprising an array of lines numbered 1 through 11,
3.8 cm in length which are separated by an angle of 18 degrees arranged in a semi- circular fashion around an imaginary locus (Benton et al., 1978). Above each reference image a pair of stimulus black lines measuring 1.9 cm are drawn in a position that represents the proximal, middle or distal half of one of the reference lines appearing below. The task is to indicate (by number) the two lines in the reference array that have the same angle and the same location as the two stimulus lines (Figure 5.1 depicts an example of a test item).
5.2.1 Scoring the Benton’s Judgment of Line Orientation task.
5.2.1.1 Global score.
Performance on the BJLO is typically reported using global scores (a maximum possible score of 30) (Benton, 1983). Benton, Varney and Hamsher
(1978) demonstrated that individuals with lesions in the right hemisphere had lower global scores than those with lesions in the left hemisphere when using global scores.
Those with left hemisphere lesions showed a performance comparable to that of healthy participants. It is expected that individuals with schizophrenia would perform more poorly on the BJLO as visual abnormities observed in schizophrenia are generally associated with right hemisphere dysfunction (Endrass et al., 2002;
Frecska, Symer, White, Piscanu & Kulcsar, 2004; Lee et al., 2005; McCourt et al.,
2008; O’Donnell et al., 2002; Park, 1999; Wynn et al., 2005).
164 Chapter 5: Benton’s Judgment of Line Orientation - An Indicator of Visuospatial Ability in Schizophrenia
Figure 5.1: An item from the Benton’s Judgement of Line Orientation (BJLO) task.
Note: The participant is required to identify the two lines from the 11-line array below that match the slope and thus orientation of the two line segments presented above.
However, the published data relating to BJLO task performance in schizophrenia are inconsistent. Some studies report poorer BJLO performance in participants with schizophrenia than control participants (Blanchard & Neale, 1994; Halari, Mehrotra,
Sharma, Ng & Kumari, 2006; Harody et al., 2004; Lee et al., 2005), whereas others report similar performance (Fleming et al., 1997; Riley et al., 2000). In these studies schizophrenia data are reported as global scores out of 30 (Benton et al., 1978), with no further line- or error-type analysis reported. It is possible that a closer examination of judgment of line-orientation performance may reveal diminished performance associated with right hemisphere dysfunction, with more errors resulting from left hemi-space lines (lines 1-5) and more horizontal and vertical line errors.
Other clinical populations have successfully been separated from controls by analysing line errors or error types in situations where between-group differences
Chapter 5: Benton’s Judgment of Line Orientation - An Indicator of Visuospatial Ability in Schizophrenia 165
were not observed when comparing global BJLO scores alone (Finton et al., 1998;
Montse, Pere, Carne, Francesc & Eduardo, 2001; Ska, Poissant & Joanette, 1990).
Differences in Alzheimer’s disease (Finton et al., 1998; Ska et al., 1990), Parkinson’s disease (Montse et al., 2001) and alcohol-related disorders (Berman & Noble, 1995) have been identified using alternative methods to analyse BJLO data. Using alternative scoring systems, similar to those proposed by (Ska et al., 1990), may prove more informative than global scores analysis reported in the schizophrenia literature to date.
5.2.1.2 Error type.
Ska, Poissant and Yves (1990) devised a method of analysing BJLO data by error type (see Table 5.1 for a detailed description). Based on the assumption that line orientation is related to dysfunction of the right hemisphere, these authors suggested it would be reasonable to expect that the cortical decline in normal ageing would affect line orientation judgment task performance. They noted from previous studies that normal ageing was associated with a moderate-but-steady decline in line orientation performance (Eslinger & Benton, 1983; Eislinger, Damasio, Benton &
Van Allen, 1985). Ska, Poissant and Yves (1990) compared global BJLO scores in a group of patients with dementia (Alzheimer’s disease) n = 11 with 95 healthy volunteers divided into three groups according to age (55-64 years, 65-74 years and
75-84 years). Global BJLO scores revealed no significant differences between groups. However, the analysis according to error type (described in Table 5.1) separated those with dementia from normal aged individuals. Chi-square analyses revealed significant differences in QO2 (an oblique confused with another oblique different by two or three spacings of 18 degrees), QO4 (both oblique lines displaced without maintaining the initial spacing) V (a vertical error involving an incorrect
166 Chapter 5: Benton’s Judgment of Line Orientation - An Indicator of Visuospatial Ability in Schizophrenia
identification of the vertical line numbered 6), H (a horizontal error involving an incorrect identification of the horizontal lines numbered 1 or 11), IQOV (a combined oblique inter-quadrant and vertical error involving the incorrect answer in combination) and IQOH (a combined oblique inter-quadrant and horizontal error involving the incorrect answer in combination ) error scores for the two groups; no healthy control participants made errors in VH, IQOV and IQOH, whereas these were common errors for participants with dementia. Ska, Poissant and Yves (1990) concluded that when a V, H, IQOV or IQOH error occur, or more than two V, H, or
IQO1 occur in a participant without visual impairment, brain dysfunction may be suspected. These results have since been replicated in other studies (Finton et al.,
1998; Simard, van Reekum & Myran, 2003) and similar findings, using this type of analysis have been reported for Parkinson’s disease (Finton et al., 1998; Montse et al., 2001).
5.2.1.3 Individual line errors.
Berman and Noble analysed individual line errors (a possible score of 60) rather than BJLO item errors (a score of 30) (Berman & Noble, 1995). Correctly identifying both lines in each item provides a measure of ‘local’ rather than ‘global’ visual information processing. Berman and Noble (1995) in examining the Taq 1A polymorphism of the DRD2 receptor gene found that boys who were A1+ (A1/A1 and A1/A2 genotypes) made a higher proportion of errors on all lines compared to those carrying the A1- (A2/A2 genotype). Thus A1+ participants were more influenced by ‘local’ than ‘global’ details based on their total line error scores.
5.2.1.4 Hemi-space errors.
Berman and Noble (1995) also grouped lines according to hemi-space as a measure of laterality differences between the groups, (left, lines 1-5 compared with
Chapter 5: Benton’s Judgment of Line Orientation - An Indicator of Visuospatial Ability in Schizophrenia 167
right, lines 7-11). Hemi-space differences were then compared according to allele status. Generally A1+ participants made more errors for the lines presented in the right hemi-space than the left, with significant between-group differences observed for right hemi-space errors. In contrast Eden et al., (1996) analysed BJLO by using hemi-space in a study to distinguish children with reading disabilities from poor readers and normal readers. They found that children with reading disabilities performed more poorly on lines presented in the left hemi-space compared to normal and poor readers. Those with reading disabilities scanned the BJLO task from the opposite direction (left to right) to that of normal readers (right to left).
5.3 Pilot Testing the Computer Version of BJLO and Alternative Scoring Systems
A computer version of the BJLO was developed along with a method of collecting and scoring BJLO data that could easily be entered into a computer database for analysis (see Appendix D for an example). A computer version of the task was considered necessary for the current study as this allowed all visual data to be collected using the same medium, under standard conditions (stimuli presented on a computer screen under laboratory conditions). This allowed the researcher to be confident that all tasks were performed using similar methods to those used in the binocular rivalry and backward-masking tasks.
168 Chapter 5: Benton’s Judgment of Line Orientation - An Indicator of Visuospatial Ability in Schizophrenia
Table 5.1: Method of analysing Benton’s Line of Judgement Orientation (BJLO) results as per (Ska et al., 1990) QO1 An oblique confused with another oblique different by only one spacing of 18
degrees
QO2 An oblique confused with another oblique different by two or three spacings of 18
degrees
QO3 Both oblique lines displaced by one or two spacings in the same direction respecting
the initial spacing
QO4 Both oblique lines displaced without maintaining the initial spacing
V A vertical error involving an incorrect identification of the vertical line numbered 6
H A horizontal error involving an incorrect identification of the horizontal lines
numbered 1 or 11
VH A vertical and horizontal error involving the simultaneous incorrect identification of
the vertical and one horizontal line
IQO1 Intra-quadrant oblique errors involving the displacement of one line from quadrant to
another quadrant
IQOV Combined oblique inter-quadrant and vertical error involving the incorrect answer in
combination (V + IQO)
IQOH Combined oblique inter-quadrant and horizontal error involving the incorrect answer
in combination (H + IQO)
Chapter 5: Benton’s Judgment of Line Orientation - An Indicator of Visuospatial Ability in Schizophrenia 169
5.3.1 Method.
5.3.1.1 Participants.
To confirm that the computer version of the BJLO yielded the same error rates as a paper version, 14 right-handed healthy volunteers were recruited from available staff at Royal Brisbane Hospital. Seven males and seven females, ranging in age from 17 to 71 years (M = 41.6 years), who all had normal vision (two had spectacle- lens-corrected vision) were presented with both the paper version and the computer version of the task.
5.3.1.2 Procedure. The computer version of the BJLO task was presented on a personal computer monitor at a distance of one metre from the participant. The background luminance was 1.398 cd/m2 (measured by Topcon BM7 Luminance Colorimeter, Japan). The paper version, in booklet form, was placed on a table in front of the participant at a distance of approximately 40 cm (comfortable working distance for the participant).
The 30 items comprising the BJLO were presented in the original prescribed order for paper version of the test (1 through 30). However, the order of the items presented in the computer version was altered to reduce the practice effect. The order of BJLO tasks (paper or computer versions) was counterbalanced across the participants to prevent potential order effects (that is, seven participants performed the computer version first, and seven the paper version first). The task was performed under free space viewing conditions with no time limit set for task completion.
To limit potential practice effects, each participant completed five practice items prior to the commencement of the task. Participants were instructed to verbally identify each line by identifying the corresponding number in the reference diagram presented below. Verbal responses were recorded by the researcher onto a
170 Chapter 5: Benton’s Judgment of Line Orientation - An Indicator of Visuospatial Ability in Schizophrenia
data collection score sheet designed to enable BJLO data to be scored according the three alternative scoring systems, that of (Benton et al., 1978; Ska et al., 1990:
Berman & Noble, 1995). This data recording system eliminated unnecessary motor involvement or interruptions in concentration by the participant, providing the researcher confidence that the results were purely related to visuospatial processing.
5.3.2 Results of pilot test
No significant difference between total number of errors were made by each participant on the computer version of the BJLO task compared with the paper version (257 and 256 respectively; t [32] = 0.50, p = .960). All participants obtained global scores that were average or better (range 26-30), according to the scoring system adopted by Benton et al., (1978), on both the computer and paper versions of the BJLO.
All participants obtained normal error scores using the scoring system developed by Ska, Poissant and Yves (1990) and had error scores consistent with those found previously for healthy participants (Finton et al., 1998; Montse et al.,
2001; Ska et al., 1990). Participants made either QO1 errors (line confused with another oblique line different by only one spacing of 18 degrees) or QO3 errors
(where both oblique lines are displaced one or two spacings in the same direction of the initial spacing) which are not suggestive of a visuospatial abnormality (Ska, et al., 1990). Participants made an average of 2.21 (SD = 1.88) QO1 errors on the computer version of the BJLO compared with 1.64 (SD = 1.78) on the paper version
(t [26] = 0.467, p = .494) and 0.07 (SD = 0.267) QO3 errors on both the computer and paper versions (t [26] = 0.00, p = 1.000).
Total number of line errors (a possible of 60 per participant), line number on which these errors occurred (1 through 11), and hemi-space errors were not
Chapter 5: Benton’s Judgment of Line Orientation - An Indicator of Visuospatial Ability in Schizophrenia 171
statistically different between the computer and paper versions of the BJLO (p>.05).
All were within the range reported in control participants by Berman and Noble
(1995). A protocol incorporating all three systems of scoring (Appendix 4), a score sheet and analyses were adopted for the major study investigating performance in schizophrenia.
5.4 Study 4, Benton’s Judgment of Line Orientation in Participants with
Schizophrenia
Based on the neurophysiologic processes underlying BJLO (for example,
(Brown, 2009; Butler & Javitt, 2005; Cadenhead et al., 1998; Goodale et al., 1994;
Ng et al., 2001; Shapiro, Hillstrom & Husain, 2002) and results described in Chapter
4, it was predicted that participants with schizophrenia would demonstrate poorer performance on the BJLO task compared to control participants. In addition, it was predicted that performance for binocular rivalry magnocellular biased stimuli and
BJLO would be correlated.
5.4.1 Aims.
There were two aims of the study. The first aim was to compare performance on a computer version of the BJLO, with respect to global scores (maximum possible score 30), line segment scores (Benton et al., 1978), individual-line error scores, hemi-space error scores (Berman & Noble, 1995), and line-type scores (Ska et al.,
1990), as an indicator of visuospatial ability in participants with schizophrenia compared to healthy controls. The second aim was to compare BJLO scores with binocular rivalry rates recorded using stimuli biased to magnocellular and parvocellular visual pathways.
172 Chapter 5: Benton’s Judgment of Line Orientation - An Indicator of Visuospatial Ability in Schizophrenia
5.4.2 Method.
5.4.2.1 Participants with schizophrenia.
Twenty-five participants with schizophrenia were recruited to the study, 20 males and five females. Of the 25 participants 17 had participated in the study as presented in Chapter 4; a further 8 participants were recruited from the outpatient clinic at Royal Brisbane Hospital. All had a DSM-IV diagnosis of schizophrenia; 11 participants had a diagnosis of paranoid schizophrenia and 14 had undifferentiated schizophrenia. Eleven participants had positive symptoms of schizophrenia, 11 negative and three had equal positive and negative symptoms (as assessed by the
PANSS). All participants with schizophrenia were taking a single dose of anti- psychotic medication (four were taking Olanzapine, six Risperidone, seven
Clozapine, three Quetiapine and five were taking typical anti-psychotics); the mean dose in chlorpromazine equivalents (CPZE) was 512 mg (SD = 286 mg).
5.4.2.2 Healthy control participants.
A total of 26 healthy control participants took part in the study.
Characteristics of participants are detailed in Table 5.2.
5.4.2.3 Procedures. The BJLO computer-based task was performed as described in Section 5.4. All participants were näive to the BJLO task and received the same instructions to complete the task. Participants were asked to verbally report the position of two lines by indicating the number of each line with respect to a reference array of lines presented directly below (see Figure 5.1). The researcher recorded the responses on the score sheet (see Appendix D). All participants completed five practice items prior to the commencement of the BJLO task. The data from the practice items were discarded.
Chapter 5: Benton’s Judgment of Line Orientation - An Indicator of Visuospatial Ability in Schizophrenia 173
Table 5.2: Age, gender, eye dominance and NART score of participants with schizophrenia and Controls.
Controls Schizophrenia χ2 df p (n=26) (n=25) Age Mean (yrs) 35.9 35.6 Range 18-58 21-54 29.525 26 .288 Gender Male 8 20 Female 18 5 12.476 1 <.001 Eye Dominance R)eye 13 17 L)eye 13 8 1.705 1 .258 NART Score Mean 117.3 116.2 Range 102-124 96-125 26.118 20 .162
5.4.3 Statistical analyses.
A power analysis was performed to determine the minimum number of participants required to demonstrate a difference in BJLO performance scores between participants with schizophrenia and healthy control groups. Data reported in (Hardoy et al., 2004) were entered into the G*power3 program (Fual et al., 2007).
It was estimated that a sample size of approximately 11 in each group was required for a two-sided 5% significance level and power of 80 to demonstrate a difference in global BJLO performance scores in schizophrenia participants compared to healthy controls.
As BJLO data was normally distributed an analysis of variance (one-way
ANOVA) was conducted. One-way ANOVA with ‘group’ as the dependent variable, revealed significant differences between the groups with respect to gender
(F[1] = 16.213, p < .001); with greater males in the schizophrenia group. There were no differences between the groups with respect to age (F [40] = 0.014, p = .907),
NART score (F [38] = 2.244, p = .142) or eye dominance (F [1] =1.695, p = .199).
174 Chapter 5: Benton’s Judgment of Line Orientation - An Indicator of Visuospatial Ability in Schizophrenia
One-way ANOVAs with ‘group’ as the dependent variable and global scores and line error scores as independent variables (adjusted for gender as per Benton,
1983) were conducted to determine group differences between global scores (Benton et al., 1978), individual line error scores, left and right hemi-space error scores
(Berman & Noble, 1995), and line type scores (Ska et al., 1990). Pearson’s correlation coefficients were used to establish whether there was an association between BJLO performance scores and binocular rivalry rates using stimuli that biased the magnocellular and parvocellular pathways. The effect of DSM-IV diagnosis and medication dose in the schizophrenia group on global score, line error scores, line segment scores, and hemi-space errors was assessed. Due to the small number of participants in each of these schizophrenia sub-groups the Chi Square (χ2) statistic was used.
5.4.4 Results.
5.4.5.1 Global score analysis.
There was a significant between-group difference in BJLO correct global score
(out of a possible 30 points) (Benton, et al., 1978). Participants with schizophrenia had lower average correct global scores on the BJLO task (ANOVA) than control participants; M = 20.92 (SD = 5.6) compared with M = 25 (SD = 2.87) for participants with schizophrenia and healthy control participants respectively (F[(1,
49] = 10.764, p = .002). When scores were adjusted for gender (as per (Benton,
1983), the overall difference increased as there were more females in the control group; schizophrenia mean correct score was 21.48 (SD = 2.96) compared with 26.46
(SD = 2.96) for healthy control participants (F[1, 49] = 5.933, p < .001). As adjustment for gender favoured the control group, increasing the already large effect, further analyses regarding line and spatial errors were conducted using raw scores.
Chapter 5: Benton’s Judgment of Line Orientation - An Indicator of Visuospatial Ability in Schizophrenia 175
Unlike previously-reported data (Benton et al., 1978; Benton, 1994; Caparelli-
Daquer et al., 2009), age, gender, NART score and eye dominance had no effect on global BJLO scores; age F(26, 24) = 0.785, p = .727, gender F(1, 49) = 0.563, p
=.457, NART score F(20, 22) =1.602, p = .142, and eye dominance F( 1, 49) =
1.116, p = .296.
Medication dose, DSM-IV diagnosis and symptom ratings (PANSS) had no effect on BJLO global scores in the schizophrenia group; (F = 0.333, df = 13, p =
.968, F = 2.13, df = 13, p = .108, F = 0.776, df = 13, p = .670, respectively).
5.4.5.2 Error type analysis.
Significant between-group differences were observed for QO1 errors (F [1, 49]
= 6.515, p = .014) and (H) horizontal errors (F[1, 49] = 4.163, p = .047) (Ska et al.,
1990). Although no other error type reached significance, participants with schizophrenia generally made more QO2 and QO4 errors than controls (F[1, 49] =
3.232, p = .078, and F[1, 49] = 3.012, p = .089 respectively). Only participants with schizophrenia made V, H, 1QOV and 1QOH errors (as reported for participants with
Alzheimer’s disease (Ska et al., 1990) and Parkinson’s disease (Montse et al., 2001).
5.5.5.3 Line error analysis.
Analyses with respect to line errors, with a maximum score out of 60 (Berman and Noble, 1995), revealed significant group differences; schizophrenia M = 48.60,
SD = 8.91) correct responses, control participants M = 54.31, SD = 3.53, F(1, 49) =
9.183, p = .004. Analyses of individual lines revealed significant group differences in error scores for Line 2, F(1, 49) = 4.294, p = .044, Line 3, F(1, 49) = 11.746, p =
.001, Line 4, F(1, 49) = 7.043, p = .011, and Line 9, F(1, 49) = 5.582, p = .022. No errors were made for Lines 1 and 6 in either group.
176 Chapter 5: Benton’s Judgment of Line Orientation - An Indicator of Visuospatial Ability in Schizophrenia
5.5.5.4 Hemi-space analyses.
To explore possible laterality differences, separate line analyses of left hemi- space (Lines 1-5) and right hemi-space (Lines 7-11) (Berman & Noble, 1995) were undertaken. There were significant group differences in both left and right hemi- space error scores. Participants with schizophrenia had lower scores in both hemi- spaces; left hemi-space mean errors, schizophrenia M = 5.0, SD = 3.81, controls M =
2.12, SD = 1.56, F(1, 49) = 12.72, p = .001; right hemi-space errors, schizophrenia M
= 6.2, SD = 4.8, controls M = 3.54, SD = 2.6), F(1, 49) = 6.12, p = .017. Participants with schizophrenia made significantly more errors in the right hemi-space (M = 6.2,
SD = 4.8) compared to the left hemi-space (M = 5.0, SD = 3.8) t (24) = -2.502, p =
.02. See Tables 5.3 and 5.4 for a summary of the results.
5.5 Association between Benton’s Judgment of Line Orientation and binocular
rivalry
Significant negative correlations between binocular rivalry rate for the magnocellular biased stimulus condition and BJLO global scores (rho =-0.471, n =
17, p = .056), and line error scores (rho = -0.483, n = 17, p = .05) were observed in participants with schizophrenia (non-parametric correlations (spearman’s rank order
- rho) were used as binocular rivalry data was not normally distributed). However, no correlations between binocular rivalry rates elicited by parvocellular biased stimuli and global BJLO scores were observed in the group with schizophrenia. No correlations were found between binocular rivalry rates (magnocellular biased and parvocellular biased) and BJLO global scores and line error scores in control participants (see Table 5.4).
Chapter 5: Benton’s Judgment of Line Orientation - An Indicator of Visuospatial Ability in Schizophrenia 177
5.6. Global score
Based on the neurophysiological processes underlying BJLO (Brown, 2009:
Butler & Javitt, 2005; Cadenhead et al., 1998; Goodale et al., 1994; Ng et al., 2001;
Shapiro et al., 2002) and results described in Chapter 4, it was predicted that participants with schizophrenia would demonstrate poorer performance on the BJLO task compared to healthy participants. Consistent with these predictions, participants with schizophrenia had significantly lower BJLO global performance scores than participants without schizophrenia (Benton et al., 1978). These data are consistent with previous studies in participants with schizophrenia (Blancharf & Neale, 1994;
Halari et al., 2006; Hardoy et al., 2004; Lee et al., 2005: Silver & Goodman, 2008).
The significant differences in global BJLO performance between participants with schizophrenia and controls observed in this study are consistent with processing in the right (and possibly left) hemisphere involving the superior parietal lobes right temporo-occipital region (Benton et al., 1975; Benton et al., 1978; Deutschm et al.,
1988; Hamsher et al., 1992; Isaacs et al., 2003; Hannay et al., 1976; Treccani et al.,
2005; Trahan, 1998; Ng et al., 2001). Low BJLO scores (< 19) have been most- frequently associated with right hemisphere dysfunction (Benton et al., 1975; Benton et al., 1978; Deutsch et al., 1998; Hamsher et al., 1992; Hannay et al., 1976; Treccani et al., 2005; Trahan, 1998; Ng et al., 2001).
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Table 5.3: Benton’s Judgement of Line Orientation (BJLO) data for control participants and participants with schizophrenia: mean global scores (out of 30 and 60), line error scores and hemi-space errors for the BJLO task.
Controls Schizophrenia
(n = 26) (n = 25) ANOVA
M SD. M SD df F p
Benton (1978)
Global Score
(30) 25 2.87 20.92 5.63 1 10.76 .002*
Berman & Noble (1995).
Total line errors (60) 54.31 3.53 48.60 8.91 1 9.183 .004*
Line 1 0 0 0 0 1 - -
Line 2 0.23 0.43 0.84 1.43 1 4.294 .044*
Line 3 0.69 0.88 1.76 1.30 1 11.84 .001*
Line 4 0.88 0.99 1.68 1.14 1 7.043 .011*
Line 5 0.27 0.45 0.44 0.71 1 1.054 .310
Line 7 0.23 0.43 0.68 1.18 1 3.312 .075
Line 8 1.77 1.37 2.44 1.83 1 2.216 .143
Line 9 1 1.06 1.88 1.56 1 5.582 .022*
Line 10 0.58 1.14 1.12 1.64 1 1.899 .174
Line 11 0.08 0.27 0.28 0.68 1 1.999 .164
L Hemi-space
Lines 1 -5 2.12 1.56 5.00 3.81 1 12.72 .001*
R Hemi-space
Lines 7 - 11 3.54 2.6 6.20 4.80 1 6.12 .017*
Note: * Indicates p < .05 significance (two tailed).
Chapter 5: Benton’s Judgment of Line Orientation - An Indicator of Visuospatial Ability in Schizophrenia 179
Table 5.4: Benton’s Judgement of Line Orientation (BJLO) data for healthy control participants and participants with schizophrenia: error type in the BJLO task
Controls Schizophrenia (n = 26) (n = 25) ANOVA M SD. M SD df F p Ska et al., (1990). QO1 4.04 2.49 5.96 2.49 1 6.515 .014* QO2 0.23 0.81 0.80 1.38 1 3.232 .078 QO3 0.54 0.86 1.08 1.63 1 2.225 .142 QO4 0.12 0.37 0.68 1.63 1 3.012 .089 V 0 0 0.8 4.0 1 1.041 .313 H 0 0 0.20 0.50 1 4.163 .047* IQO1 0.04 0.19 0.32 1.41 1 1.023 .317 IQOV 0 0 0.08 0.40 1 1.041 .313 IQOH 0 0 0.08 0.40 1 1.041 .313 Note: * Indicates p < .05 significance (two tailed).
In addition, it was predicted that performance would be correlated for binocular rivalry magnocellular biased stimuli and BJLO. This association supports the notion that the dorsal stream influences the rate of alternation of perceptual images in binocular rivalry, thus supporting the notion of ‘bottom up’ visual processing (Butler et al., 2007). Although this is a simplistic view, as there is much interaction between the magnocellular and parvocellular pathways with the dorsal and ventral streams each receiving inputs from both pathways (Goodale & Milner, 1992; Shapley, 1990;
Shapiro et al., 2002), these data add to a large body of work that demonstrates functional and behavioural divisions for processing spatial relationships and object recognition (Brown, 2009; Butler & Javitt, 2005; Cadenhead et al., 1998; Goodale et al., 1994; Popken, Bunney, Potkin & Jones, 2000). Furthermore, characteristic visuospatial deficits in schizophrenia are largely attributed to the magnocellular or
180 Chapter 5: Benton’s Judgment of Line Orientation - An Indicator of Visuospatial Ability in Schizophrenia
dorsal stream (Cadenhead et al., 1998; Doinger et al., 2002; MClure, 2001; Schechter et al., 2003).
Table 5.5: Correlations between global Benton’s Judgement of Line Orientation (BJLO) scores and binocular rivalry (BR) rates for stimuli that bias the BR task for either the magnocellular or parvocellular visual pathways (spearman rank order).
BR rate - Magnocellular BR rate - Parvocellular
Stimuli Stimuli
rho p n rho p n
Control participants
Global scores (30) 0.183 .426 21 0.360 .109 21
Line error scores (60) 0.181 .432 21 0.411 .064 21
Schizophrenia Participants
Global scores (30) -0.502 .04* 17 -0.282 .257 17
Line error scores (60) -0.483 .05* 17 -0.312 .207 17
Note. * Indicates p < .05
The findings of other studies indicate that participants with schizophrenia have abnormalities in one (or both) of these visual pathways (Brown, 2009; Butler &
Javitt, 2005; Cadenhead et al., 1998; Doinger et al., 2002; Goodale et al., 1994;
McClure, 2001; Popken et al., 2000;Schechter et al., 2003) and one (or both) of the cerebral hemispheres (Endrass et al., 2002; Evans & Schwartz, 1997; Frecska, Symer et al., 2004; Gastaldo et al., 2002; Levander et al., 1985; McCourt et al., 2008; Narr,
Green, Capetillo-Cunliffe, Toga & Zaidel, 2003; O’Donnell et al., 2002; Park, 1999;
Schwartz et al., 1984; Wynn et al., 2005). Data presented in Chapter 4 of this thesis provides further evidence for this position.
Chapter 5: Benton’s Judgment of Line Orientation - An Indicator of Visuospatial Ability in Schizophrenia 181
5.7.1.1 Error type.
Significant between-group differences were observed for QO1 errors suggestive of poorer overall global processing in schizophrenia. Although no other error type reached significance, participants with schizophrenia generally made more
QO2 and QO4 errors than controls. A previous study noted that QO2 and QO4 errors distinguished participants with dementia from controls (Ska et al., 1990), thus some degeneration of cortical visual processing may occur in Schizophrenia. Only participants with schizophrenia made V, H, 1QOV and 1QOH errors, consistent with previous reports in Alzheimer’s disease (Simard et al., 2003; Ska et al., 1990) and
Parkinson’s disease (Montse et al., 2001). Ska et al., (1990) suggest that a participant without primary visual impairment may be suspected to have some brain dysfunction when type VH, 1QOV, or 1QOH errors occur, or more than two, type V,
H or 1QO1 errors occur. Two participants with schizophrenia made errors that would indicate some form of brain dysfunction consistent with the position made by
(Ska et al., 1990); one participant with schizophrenia made two H and two 1QOH errors, and another made two 1QOH errors and seven 1QO1 errors.
It is generally agreed that the visuospatial abnormalities elicited by the BJLO task observed in ageing populations, such as Alzheimer’s and Parkinson’s Disease, are related to dopamine depletion (Finton,et al., 1998; Montse et al., 2001; Ska et al.,
1990). Participants with Parkinson’s disease, a condition where reduced dopamine is neuropathological, are reliably separated from normal participants with the BJLO task. Schizophrenia is also considered to be a disease related to dopamine, with many authors suggesting schizophrenia to be a hyper-dopaminergic disorder
(Hirvonen et al., 2005; Seeman & Kapur, 2000). It would be reasonable to assume
182 Chapter 5: Benton’s Judgment of Line Orientation - An Indicator of Visuospatial Ability in Schizophrenia
that specific intra-quadrant errors on the BJLO task made by participants with schizophrenia were indicative of dopamine related visuospatial abnormalities.
5.7.1.2 Hemi-space.
Participants with schizophrenia made significantly more errors in each hemi- space than did healthy controls. These results are consistent with a large body of work indicating overall visual abnormalities in schizophrenia related to hemi-space presentation of visual data to stimulate the left and right visual hemispheres. Deficits in left and right hemispheric visual processing in schizophrenia have been noted in a variety of visual tasks associated with spatial perception and attention (O’Donnell et al., 2002), sustained attention (Evans & Schwartz, 1997) selective attention
(Holzman, 1987) working memory, (Park, 1999), and detecting visual information
(Schwartz et al., 1994).
Participants with schizophrenia in this sample made significantly more right hemi-space errors compared to left, however control participants also made more right than left hemi-space errors. Right hemi-space errors are generally processed by the left hemisphere, and this is opposite to the hemisphere thought to be typically most effected in schizophrenia. However, it should be noted that significant differences were found between the groups for Lines 2, 3 and 4, which are left hemi- space presentations and only one of right hemi-space presentation, Line 9. The results reported here support the notion that visuospatial information is processed within each cortical hemisphere. Tranel et al., (2009) make the point that although the BJLO is considered to be subjected to predominantly processing in the right hemisphere, fMRI and lesion studies also indicate some left hemisphere involvement. There is a large body of evidence to support the right hemisphere being the ‘dominant’ or ‘preferred’ system for processing visuospatial information.
Chapter 5: Benton’s Judgment of Line Orientation - An Indicator of Visuospatial Ability in Schizophrenia 183
5.7.2 Potential Impact of BJLO Performance
5.7.2.1 Age and gender.
The results recorded by controls were within previously established population norms (Benton, 1983). No age or gender effects were seen on global performance scores or individual line and line spacing errors in this study, although age and gender have been reported to impact on BJLO in previous studies (Collaer & Nelson,
2002; Montse et al., 2001; Woodard et al., 1998). Normative standards of performance for the BJLO for age and sex have been established by Benton and correcting global scores for age and gender increases these group differences further
(Benton, 1983). Interpreting BJLO performance data on the basis of age and gender is limited as age- and sex-matched samples were not used in this study.
5.7.2.2. Medication effects.
The type of anti-psychotic medication taken and anti-psychotic dose, based on
CPZEs had no effect on BJLO scores in participants with schizophrenia. These data are consistent with other studies reporting no medication effect on BJLO performance (Buchanan, Holstein & Breier, 1994; Halari et al., 2006; Riley et al.,
2000; Sweeney, Hass, Keilp & Long, 1991). Double-blind studies have also observed that BJLO performance was not different in participants with schizophrenia either after twelve weeks of treatment with Clozapine or Haloperidol, or after twelve months of treatment with Clozapine (Buchanan et al., 1994).
5.7.2.3 Schizophrenia sub-types and symptom ratings.
Schizophrenia sub-types (whether the participant had paranoid schizophrenia or undifferentiated schizophrenia) and symptomology (negative or positive schizophrenia measured by PANSS) had no effect on BJLO scores. This was expected as BJLO performance has been found not to be related to the symptoms of
184 Chapter 5: Benton’s Judgment of Line Orientation - An Indicator of Visuospatial Ability in Schizophrenia
schizophrenia (Buchanan et al., 1994; Riley et al., 2000). Furthermore, all the participants with schizophrenia in this cohort were relatively stable on current medication and living in community settings. Greater differences may have been seen in a more symptomatic cohort of participants.
5.7.2.4 Cognitive ability.
It may be that differences in BJLO performance scores are related to general cognitive decline in schizophrenia (Fleming et al., 1997; Halari et al., 2006; Lee et al., 2005; Trahan, 1998). It is unlikely that the differences in BJLO are attributed solely to cognitive ability as NART (a measure of pre-morbid cognitive functioning) scores were not found to be significantly different between the two groups in this sample (as found in the previous chapters).
5.7.3 Comparing Benton’s Judgment of Line Orientation with Binocular Rivalry
Significant negative correlations between binocular rivalry rate in the magnocellular stimulus condition and BJLO global scores were found only in participants with schizophrenia. This faster binocular rivalry rate in participants with schizophrenia was associated with fewer BJLO errors. In the previous three chapters, a slower binocular rivalry rate was demonstrated over a range of stimulus conditions in participants with schizophrenia, which has been interpreted as an abnormal binocular rivalry rate. Taking this together with the results of the current chapter suggest that this slower binocular rivalry rate is an indication of reduced visuospatial ability in schizophrenia largely attributable to magnocellular processing or functions of the dorsal visual pathway (Butler & Javitt, 2005; Doniger et al., 2002;
McClure, 2001; Schechter et al., 2003). In participants with schizophrenia, no significant correlations were evident between binocular rivalry rates elicited by parvocellular binocular rivalry stimuli, perhaps suggesting that ventral visual
Chapter 5: Benton’s Judgment of Line Orientation - An Indicator of Visuospatial Ability in Schizophrenia 185
processing was not a feature of binocular rivalry. However, this is unlikely as slow binocular rivalry rate and abnormal backward-masking performance were observed in schizophrenia when using stimuli that biased the parvocellular pathways in the previous chapter. Previous published studies (Brown, 2009; Butler & Javitt, 2005;
Cadenhead et al., 1998; Doniger et al., 2002; Goodale et al., 1994; McClure, 2001;
Popken et al., 2000; Schechter et al., 2003) also indicate that participants with schizophrenia have abnormalities in one (or both) of these visual pathways and one
(or both) of the cerebral hemispheres (Endrass et al., 2002; Evans & Schwartz, 1997;
Ferecska, Symer et al., 2004; Gastaldo et al., 2002; Levander et al., 1985; McCourt, et al., 2008; Narr et al., 2003; O’Donnell et al., 2002; Park, 1999; Schwartz et al.,
1984; Wynn et al., 2005).
5.7.4 Cortical Pathway and Hemispheric Models of Involvement
5.7.4.1 Dorsal and Ventral Pathways
No association was found between binocular rivalry rates for both the magnocellular or parvocellular biased tasks and BJLO global or hemi-space scores in control participants. To be confident that binocular rivalry rate was attributable to processing via the dorsal stream it would be expected that binocular rivalry rates elicited from magnocellular binocular rivalry stimuli would also correlate with BJLO global scores in these participants. This lack of correlation must therefore be interpreted cautiously. Although the ventral stream receives some magnocellular input, the magnocellular pathway provides the dominant initial input to the dorsal necessary for processing movement and spatial location information; the prominent feature of the dorsal stream (Brown, 2009). Moreover, it has been noted using brain mapping techniques that the normal adult dorsal stream in humans has additional intra- and inter-hemispheric connections (Loenneker et al., 2010). Dorsal fibres
186 Chapter 5: Benton’s Judgment of Line Orientation - An Indicator of Visuospatial Ability in Schizophrenia
penetrate into contralateral hemispheres via commissural structures and projection fibres that extend to the superior temporal gyrus and ventral association pathways, with intra-hemispheric connectivity being particularly strong in the dorsal stream of the right hemisphere (Loenneker et al., 2010). If binocular rivalry is subject to magnocellular or dorsal stream processes, it is conceivable that the slow binocular rivalry rate in schizophrenia may be related to the slow exchange of visuospatial information from one hemisphere to the other.
As stated previously, the BJLO is considered a task involving predominantly right cortical hemisphere processes. Performance on the BJLO in individuals with schizophrenia was poorer than in control participants, suggesting abnormal processing of the ‘Where is it?’ system, the magnocellular pathway/dorsal stream.
Although it is likely the parvocellular or ventral system is also involved in binocular rivalry. The results presented in Chapter 4 and in the current chapter suggest that the magnocellular or dorsal stream plays a prominent role in visuospatial processing in schizophrenia. Binocular rivalry may therefore be reliant on intact magnocellular or dorsal systems, with abnormalities slowing the alternation between opposing perceptual images.
5.7.4.2 The Cortical Hemispheres
Poorer performance on BJLO task was suggestive of impaired right hemisphere processing in schizophrenia. Individuals with schizophrenia also performed more poorly in binocular rivalry tasks. Rather than an ‘inter-hemispheric switch’ driving binocular rivalry (Funk & Pettigrew, 2003; Miller et al., 2000; Miller, 2001;
Pettigrew & Miller, 1998), it may be that interactions between magnocellular (or dorsal stream) and parvocellular (or ventral stream) processing spatial and temporal information from the rival stimuli within the hemisphere drive binocular rivalry.
Chapter 5: Benton’s Judgment of Line Orientation - An Indicator of Visuospatial Ability in Schizophrenia 187
Prefrontal cortical involvement is not necessary to generate binocular rivalry, suggesting this is a locally-driven process resolved ‘lower down’ in the visual pathway within each hemisphere (Calle-Inclan & Gallego, 2006). Interaction between the ventral and dorsal streams lower in the visual pathways would explain why binocular rivalry is able to occur in split-brain observers (O’Shea, Corballis,
2005b; O’Shea & Corballis, 2003).
5.6 Conclusion
A significant difference was measured between participants with schizophrenia and control participants in BJLO global scores (Benton et al., 1978; Berman &
Noble, 1995), individual line error scores, line segment scores (Berman & Noble,
1995), hemi-space error scores (Benton et al., 1978), and line type scores (Ska et al.,
1990). These data suggest overall abnormalities in visuospatial ability in participants with schizophrenia. Cognitive ability (measured by the NART), age, medication dose, DSM-IV diagnosis and symptom ratings (PANSS) had no effect on BJLO global scores, line error scores, line segment scores, and hemi-space errors in the schizophrenia group, suggesting that the abnormalities demonstrated are due to visuospatial processing in schizophrenia. Visuospatial processing is considered to be predominantly processed by structures within the right cortical hemispheres, involving the magnocellular or dorsal pathway systems. These results are consistent with previous studies in schizophrenia.
These results presented in this chapter, considered together with the results of the previous chapter, indicate that the binocular rivalry may be initiated by competition between the magnocellular and parvocellular pathways within (rather than between) each cortical hemisphere. If this is the case the mechanisms involved in binocular rivalry would be distributed throughout the visual hierarchy. Abnormal
188 Chapter 5: Benton’s Judgment of Line Orientation - An Indicator of Visuospatial Ability in Schizophrenia
binocular rivalry rate thus indicating processing and information transfer abnormalities at all levels of visual processing (i.e. involving occipital, parietal, temporal and frontal cortical structures). It is pertinent to investigate the role that neurotransmitters would have in these processes.
The neurotransmitter most frequently associated with schizophrenia is dopamine. Given that dopamine is also responsible for moderating many functions within the visual system, it is reasonable to expect that some of the visual abnormalities seen in schizophrenia, and perhaps binocular rivalry to be associated with dopamine. In the following chapter (Chapter 6), the role of dopamine in visual processing is examined.
Chapter 5: Benton’s Judgment of Line Orientation - An Indicator of Visuospatial Ability in Schizophrenia 189
Chapter 6: Taq1 allele of the DRD2 dopamine receptor gene, binocular rivalry, visual
backward masking and Benton’s Judgment of Line Orientation
6.1 Dopamine in Vision
It is well established that dopamine plays a role in human visual processing
(Brandies & Yehuda, 2008; Bodis-Wollner, 2009; Djamgoz, Hankins, Hirano &
Archer, 1997; Masson et al., 1993; Witovsky, 2004). Many patients with
Parkinson’s disease, a disorder of diminished dopamine function are demonstrated to have abnormal VEPs, and therapy with dopamine precursors has been shown to improve the evoked potentials (Bodis-Wollner, 1997). Conversely, drugs with dopamine-blocking properties delay the normal VEPs in sufferers of schizophrenia
(Bodis-Wollner, 1988). Using animal models (monkeys), when VEPs were measured pre- and post-administration of sulpiride (a dopamine D2 antagonist), the
P100 component of the VEP decreased, while the amplitude of the cognitive P300 component decreased (Antal, Keri & Bodis-Wollner, 1997). This suggests that D2 receptors play a major role in visuo-cognitive processes in dopamine-related conditions, such as Parkinson's disease and schizophrenia. The progressive loss of colour discrimination and contrast sensitivity in Parkinson’s disease (Crevits, 2003;
Diederich, Raman, Leurgans & Foetz, 2002; Zahodne & Fernandex, 2008) that occurs with depletion of dopamine receptors in the retina and visual pathways with age has also been suggested to be due in part to D2 depletion.
Animal models have provided evidence that density and frequency of D2 dopamine receptors found in the retina and primary visual pathway are similar to those in the primate striate cortex (Djamgoz et al., 1997; Schorderet & Nowak, 1990;
Witkovsky, 2004). Therefore, a better understanding of function of dopamine and
D2 receptors in the retina and striatum provides a unique opportunity to examine
Chapter 6: Taq1 allele of the DRD2 dopamine receptor gene, binocular rivalry, visual backward masking and Benton’s Judgment of Line Orientation 190
neurotransmitter involvement in visual neurocognitive processing along the visual pathways (Bodis-Wollner & Antal, 1995).
6.1.1 The A1 allele of the DRD2 receptor gene.
Given this interest in D2 receptors within the visual system, and that schizophrenia has been associated with abnormal D2 receptor density and functioning, it is plausible to examine visual processing according to genetic variations in D2 receptors. Dopamine receptor genes that have commonly been investigated in neuropsychiatric diseases, including schizophrenia, include DRD2,
DRD3 and DRD4 receptor genes and their polymorphisms (Talkowski, Bamme,
Hader & Nimgaonkar, 2007; Ohara, 1996). The TaqI A of dopamine D2 receptor
(DRD2) gene is a commonly investigated gene in schizophrenia (Behravan,
Hemayatkar, Toufani, & Abdollahian, 2008), with data available relating to functional interactions of the gene (Matsumoto et al., 2005: Mihara et al., 2003), making it a promising genetic variant to explore. The TaqI A of dopamine D2 receptor (DRD2) gene has been mapped to an adjacent kinase gene and is also sometimes referred to as ANKK1.
Carriers of TaqI A of dopamine D2 receptor (DRD2) gene (A1+ individuals with A1/A1 or A1/A2 genotypes) typically have a lowered DRD2 density and diminished function of DRD2 in the striatum, (Kondo et al., 2003; Mihara, Kondo et al., 2000; Nobel, 2000). The human dopamine D2 receptor gene (DRD2) has been posited as a candidate gene for neuro-psychiatric disease (Finckh et al., 1996; Noble,
2000; Noble, 2003). This has been associated with Tourette's syndrome, post- traumatic stress disorder (PTSD) and certain symptoms associated with affective disorders and schizophrenia, Parkinson's disease and iatrogenically-induced movement disorders (Noble, 2000). It is hypothesised that the DRD2 is a
Chapter 6: Taq1 allele of the DRD2 dopamine receptor gene, binocular rivalry, visual backward masking and Benton’s Judgment of Line Orientation 191
reinforcement or reward gene, as variants of the DRD2 gene have been associated with addictive disorders, including alcoholism (Blum et al., 1991; Blum et al., 1993), cocaine, nicotine and opioid dependence (Laruelle, Gelenter & Innis, 1998; Noble,
2003; Young, Lawford, Nutting & Noble, 2004) and obesity (Noble, 2003).
The A1 allele of the DRD2 gene has been found in post-mortem studies to be over represented in patients with schizophrenia (Noble, 2000; Noble, 2003).
However association studies in schizophrenia generally show no relationship
(Behravan, Hemayatkar, Toufani & Adbollahian, 2008; Suzuki, Kondo et al., 2000;
Parsons et al., 2007; Ohara et al., 1996; Kishida et al., 2003), suggesting the A1 allele acts as a modifying gene in schizophrenia rather than being of primary aetiological significance (Comings et al., 1991).
A1+ individuals generally have more symptoms of schizophrenia (Ohara et al.,
1996; Sanjuan et al., 2004) and are at greater risk of significant adverse effects
(Alenius et al., 2008; Kaiser, Tremblay, Klufmoller, Roots & Brookmoller, 2002).
They tend to suffer more extra-pyramidal symptoms (Guzey, Scordo, Spina,
Landsem & Spigset, 2007; Mihara, Suzuki et al., 2000, Kaiser et al., 2002;
Hedenmalm, Guzey, Dahl, Yue & Spigset, 2006; Young, Lawford et al., 2004), and are more at risk of tardive dyskinesia (Chen, Wei, Koong & Hsiao, 1997), polydipsia
(Matsumoto, et al., 2005) and neuroleptic malignant syndrome (Mihara et al., 2003;
Suzuki et al., 2001). These findings have been confirmed in most studies. Mihara et al., (2000) found that A1+ female patients were at greater risk of developing neuroleptic-induced hyperprolactinemia, and had increased serum prolactin when treated with bromocriptine (a dopamine agonist) (Mihara, Kondo et al., 2000; Mihara et al., 2001).
192Chapter 6: Taq1 allele of the DRD2 dopamine receptor gene, binocular rivalry, visual backward masking and Benton’s Judgment of Line Orientation
Although A1+ individuals with schizophrenia tend to experience more adverse effects, the general consensus is they also tend to have more favourable responses to medication (Schargetter, 2004). A1+ individuals show greater improvement in total
Brief Psychiatric Rating Scale (BPRS) scores and in positive symptoms with anti- psychotic treatment (Suzuki, Mihara et al., 2000). A1+ individuals are also more likely to benefit from anti-psychotics with weaker dopamine D2 receptor antagonistic properties (Alenius et al., 2008).
Investigations into the effect of anti-psychotic medications in schizophrenia in the presence of the A1 allele indicate that this polymorphism may modify the efficiency of DRD2 antagonism of the drugs in the central nervous system (Suzuki,
Mihar, et al., 2000). Higher serum prolactin levels, as an indicator or dopamine D2 receptor blockade (Cotes et al., 1977; Gruen, 1978; Seeman, 2002), have been found in A1+ carriers with schizophrenia receiving anti-psychotic medications compared to those without. Furthermore, A1 + individuals were over-represented in those with hyperprolactinemia (Young, et al., 2004).
In disorders associated with depleted dopamine, for example Parkinson’s disease, the Taq1 A polymorphism has been investigated (Bartres-Faz et al., 2007;
Oliveri et al., 2000). Researchers investigating this gene in Parkinson’s disease propose that the genetic variation in the DRD2 gene influences the risk of developing
Parkinson’s disease, and therefore is a susceptibility locus for Parkinson’s disease
(Oliveri et al., 2000; Grevle et al., 2000), rather than a modifying gene. However, imaging (fMRI) studies have revealed that larger networks of bilateral cerebral areas, including cerebellar and pre-motor regions, are involved in complex sequential motor tasks in A1+ individuals with Parkinson’s disease than A1- individuals, regardless of medication treatment (Bartres-Faz et al., 2007). This is more suggestive of a trait-
Chapter 6: Taq1 allele of the DRD2 dopamine receptor gene, binocular rivalry, visual backward masking and Benton’s Judgment of Line Orientation 193
like feature, rather than a modifying effect of the allele. Furthermore, the presence of the A1 allele had no significant impact on the efficacy of Pramipexole in treating patients with Parkinson’s disease (Liu et al., 2009), again suggesting a trait-like feature. In other memory-impaired older adults, for example those with Alzheimer’s disease, the A1- Status has been associated with diminished cognitive performance and increased atrophy in the striatum (Bartres-Faz et al., 2002). However, while the
A1 allele of the DRD2 receptor gene may be a trait marker for Parkinson’s disease, a larger amount of evidence suggests that this gene acts as a modifying gene in schizophrenia.
6.1.2 The A1 allele of the DRD2 receptor in vision.
The A1 allele may have a moderating effect on visuospatial processing in schizophrenia. Berman and Noble (1995) reported significantly-reduced visuospatial performance in children with the A1 allele of the D2 dopamine receptor (DRD2) gene. A1 + boys made more errors than A1- boys (Berman & Noble, 1995; Berman
& Noble, 1997), whereas A1- boys showed latency in the P300 wave of VEPs
(Berman et al., 2006). Girls with the A1+ status have demonstrated poorer visuospatial functioning than that of boys with the A1+ status (Berman et al., 2003).
Because no statistically significant association between the A1 allele and IQ has been demonstrated (Petrill et al., 1997), these authors suggest that the DRD2 receptor gene association is specific to visuospatial performance and independent of general cognitive ability.
The Taq 1A polymrphism of the DRD2 dopamine receptor gene therefore provides a putative model to investigate whether the differences in binocular rivalry rate and poorer performance on VBM and BJLO tasks in the group of schizophrenia subjects, compared with healthy controls.
194Chapter 6: Taq1 allele of the DRD2 dopamine receptor gene, binocular rivalry, visual backward masking and Benton’s Judgment of Line Orientation
6.2 Aims
The primary aim of this study was to determine whether DRD2 Taq 1A status was associated with binocular rivalry, backward masking and BJLO tasks performance. The second aim is to determine whether A1+ (A1A1 and A1A2 genotype) participants with schizophrenia performed more poorly on binocular rivalry, backward masking and the BJLO tasks than those participants with schizophrenia with A1- (A2A2 genotype) status.
6.3 Method
6.3.1 DNA collection and extraction.
Participants were asked to provide 2 mls of saliva for DNA extraction. Saliva samples were collected using an Oragene.DNA® (DNA Genotek, Ontario, Canada) collection tube. Collection tubes were stored at room temperature until the DNA was extracted as per the manufacturer’s instructions.
Genomic DNA was extracted employing standard techniques and used as a template for determination of Taq1 A DRD2 alleles by the polymerase chain reaction
(Grandy, Zhang & Civelli, 1993). A Perkin Elmer GeneAmp 9600 Thermocycler was used in the amplification of DNA. Approximately 500 mg of amplified DNA was digested with five units of Taq1 restriction enzyme (New England Biolabs) at
65oC overnight. The resulting products were separated by electrophoresis in a 2.5% agarose gel containing ethidium bromide and visualized under ultraviolet light. The
Taq1 A DRD2 alleles were identified as described in Lawford, et al., (2005). Three genotypes were obtained. The A1A2 genotype was revealed by three fragments: 310,
180 and 130 base pairs (bp), the A2A2 genotype was shown by two fragments: 180 and 130 bp and the A1A1 genotype was revealed by the uncleaved 310 bp fragment.
Chapter 6: Taq1 allele of the DRD2 dopamine receptor gene, binocular rivalry, visual backward masking and Benton’s Judgment of Line Orientation 195
As noted, A1+ allele participants have either A1A1 or A1A2 genotypes whereas the
A1- participants have only the A2A2 genotype.
6.3.2 Participants.
Thirty-three control participants were recruited to participate in the study (20 participated in the study described in Chapter 2, of these 14 participated in the study described in Chapter 3, with a further six participants recruited specifically for the current study). Seven further participants were recruited to the current study from the study detailed in Chapter 4. Of these, 29 provided a saliva sample and four declined to provide a sample. One participant’s DNA sample had degenerated (due to a compromised seal on the collection tube) so their DNA was unable to be amplified.
Twenty-five participants with schizophrenia were recruited to the study.
Twenty participants completed the study described in Chapter 3, of these 17 provided a sample of salvia for DNA extraction and three refused. A further five participants were recruited to the studies detailed in Chapters 4 and 5, however only one additional saliva sample was obtained; the four remaining participants did not consent to DNA extraction.
Genotype and allelic information were available for 46 participants (18 with schizophrenia and 28 controls). DNA data were not available for seven participants with schizophrenia and five healthy subjects. The participants who did not provide
DNA did not differ to the larger group with respect to age, gender, dominant eye or
NART scores (Mann-Whitey U, p > .05).
196Chapter 6: Taq1 allele of the DRD2 dopamine receptor gene, binocular rivalry, visual backward masking and Benton’s Judgment of Line Orientation
6.3.2.1 Control participants who participated in the binocular rivalry tasks in
Study 1.
Of the 20 control participants who participated in Study One (Chapter 2) 16 were genotyped for the presence of the A1 allele of the DRD2 receptor gene; five were identified as A1+ and 11 as A1-. Of the five who were identified as A1+, all were female, three were right-eye dominant, two left-eye dominant, and had an average age of 42.4 years (range 22-60 years) and an average NART score of 116.8
(range 114-122). Of the 11 as classified as A1-, four were male, seven female, seven were right-eye dominant, four left-eye dominant with an average age of 39.3 years
(range 22-64 years), and average NART score of 116.1 (range 108-121). There were no significant group differences in gender (U = 58, Z = -1.508, p =.132), eye dominance (U = 49, Z = -1.891, p = .059), age (U = 78.5, Z=-0.79, p = .937) or
NART score (U = 56, Z = -0.260, p = .795).
6.3.2.2 Participants with schizophrenia and healthy controls who participated
in binocular rivalry, Studies 2 and 3 and the Necker Cube task in Study 2
(Chapters 3 and 4).
Of the 24 genotyped control participants who participated in the binocular rivalry tasks described in Chapters 3 and 4, seven were A1+ and seventeen A1-; the average age 39.8 years (range 18-64 years) with an average NART score of 116.9
(range 105-122).
Of the 17 genotyped participants with schizophrenia, five were A1+ and twelve
A1-; the average age 34.76 years (range 23-51years) with an average NART score of
111.6 (range 101-121). See Table 6.1 for the breakdown of age, gender, eye dominance and mean NART score according to Allele status.
Chapter 6: Taq1 allele of the DRD2 dopamine receptor gene, binocular rivalry, visual backward masking and Benton’s Judgment of Line Orientation 197
6.3.2.3 Participants with schizophrenia and healthy controls who participated
in visual backward masking tasks in Study 3 (Chapter 4).
Of the genotyped control participants who participated in the VBM tasks Four were classified as A1+ and ten A1-; the average age 36.4 years (range 21-58) and an average NART score was 113.5 (range 104-121).
Of the genotyped participants with schizophrenia who participated in the VBM tasks, four were A1+ and eight were A1-; the average age 33.9 years (range 23-50 years) with an average NART score of 111.6 (range 101-121). See Table 6.1 for the breakdown of age, gender, eye dominance and mean NART score according to
Allele status.
6.3.2.4 Participants with schizophrenia and healthy controls who participated
in Benton’s Judgment of Line Orientation in Study 4 (Chapter 5).
Of the 20 healthy participants genotyped, eight were A1+ and twelve were
A1-; the average age 35.9 years (range 18-58 years) with an average NART score of
116.4 (range 102-124).
Of the 18 genotyped participants with schizophrenia who participated in the
BJLO, six were A1+ and twelve A1- ; the average age 34.2 years (range 21-51 years) with an average NART score of 111.9 (range 96-124). See Table 6.1 for the breakdown of age, gender, eye dominance and mean NART score according to
Allele status.
198Chapter 6: Taq1 allele of the DRD2 dopamine receptor gene, binocular rivalry, visual backward masking and Benton’s Judgment of Line Orientation
Table 6.1: Demographic characteristics of participants genotyped for the presence of the Taq1 A DRD2 alleles receptor for studies 2, 3 and 4.
Study 2 Study 3 Study 4 A1+ A1- A1+ A1- A1+ A1- Controls (n=7) (n=17) (n=4) (n=10) (n=8) (n=12) Age (mean yrs) 38.5 39.8 33.6 37.8 38.4 38.7 Male 0 5 0 4 1 6 Female 7 12 4 6 7 6 L)eye dominant 4 6 3 2 7 4 R)eye dominant 3 11 1 8 1 8 NART (mean) 116.7 116.9 116.8 117.6 117.7 118.2
A1+ A1- A1+ A1- A1+ A1- Schizophrenia (n=5) (n=12) (n=4) (n=8) (n=6) (n=12) Age (mean yrs) 29.7 36.9 31 36.3 29.7 35.3 Male 2 9 3 6 3 10 Female 3 3 1 2 3 2 L)eye dominant 2 5 2 5 2 5 R)eye dominant 3 7 2 3 4 7 NART (mean) 110.7 114.8 111.8 114.4 110.7 112.3 CPZE (mg) 425 540 410 555.6 425 583.3
6.4 Results
6.4.1 Binocular rivalry results.
6.4.1.1 Binocular rivalry in control participants in 16 stimulus Conditions from
Study 1.
There were no differences in binocular rivalry rates recorded by A1+ control participants (n = 5) and A1- control participants (n = 11) over the 16 stimulus conditions in Study 1 described in Chapter 2 (Mann-Whitney U, p > .05). See Table
6.2 for results.
Chapter 6: Taq1 allele of the DRD2 dopamine receptor gene, binocular rivalry, visual backward masking and Benton’s Judgment of Line Orientation 199
Furthermore, allelic status did not account for differences in the range of binocular rivalry scores observed in Table 2.1 in Chapter 2. A1+ participants’ binocular rivalry rates ranged from 0.15 to 0.89 Hz, whereas those with A1- status ranged from 0.23 to 1.0 Hz (Mann-Whitney U = 22.0, Z=-. 623, p=.583). The median binocular rivalry rates for A1+ participants were 0.478 Hz, compared with
A1- median binocular rivalry rates of 0.453 Hz (Mann-Whitney U = 25.0, Z = -. 283, p = .827).
6.4.1.2 Binocular rivalry rates in low- and high-strength, magnocellular and
parvocellular biased binocular rivalry tasks and the Necker cube.
There were no group differences in binocular rivalry rates recorded in A1+ (n =
13) and A1- (n = 28) participants (Mann-Whitney U, p > .05). When participants with schizophrenia were considered separately from control participants, those who were A1+ (n = 6) generally recorded slower binocular rivalry rates than A1- (n = 11) participants, and there a statistical trend in the magnocellular biased binocular rivalry task (Z = -1.764, p = .078). However, no other statistical differences were observed in any other binocular rivalry stimulus. No differences in binocular rivalry rates were observed between A1+ (n = 7) and A1- (n = 17) healthy participants (Mann-
Whitney U, p > .05). See Table 6.3 for results.
6.4.2 Backward masking results.
No differences between allelic groups were evident in the backward masking scores in either participants with schizophrenia (A1+ n = 4, A1- n = 8) or control participants (A1+ n = 4, A1- n = 10). See Table 6.4 and 6.5 for results.
6.4.3 Benton’s Judgment of Line Orientation Task results.
Subjects with schizophrenia in this sample who had A1+ (n = 6) status performed more poorly on the BJLO than those who were A1- (n = 12); M = 45.17,
200Chapter 6: Taq1 allele of the DRD2 dopamine receptor gene, binocular rivalry, visual backward masking and Benton’s Judgment of Line Orientation
SD = 8.7 correct compared to M = 47.1 SD = 8.7, respectively. Analysis of individual lines revealed that A1+ participants with schizophrenia made more errors on Line 10 (M = 2.0, SD= 1.7 compared to M = 1.0, SD= 2.0; χ2 [1, 18] =13.95, p =
.016) than those with A1- status. A1- participants with schizophrenia made more errors on Lines 3, 4, 8 and 9, but these differences failed to reach significance.
Table 6.2: Binocular rivalry rates recorded by A1+ healthy participants (n = 5) compared A1- healthy participants (n = 11) over the 16 stimulus conditions.
Healthy Controls
A1+ Allele (n=5) A1- Allele (n=11)
Median Range Median Range U Z p
L4AS 0.300 0.634 0.283 0.325 24 -0.397 .743 L4AM 0.350 0.841 0.400 0.516 21 -0.737 .510 L4CS 0.250 0.567 0.280 0.391 24 -0.397 .743 L4CM 0.400 1.009 0.408 0.498 26 -0.170 .913 L8AS 0.192 0.583 0.375 0.842 18 -1.077 .320 L8AM 0.275 0.700 0.500 0.558 23 -0.510 .661 L8CS 0.283 0.584 0.200 0.808 26 -0.170 .913 L8CM 0.233 0.775 0.317 0.633 27 -0.057 1.000 H4AS 0.333 0.734 0.467 0.800 22 -0.623 .583 H4AM 0.467 0.850 0.492 0.683 26 -0.170 .913 H4CS 0.530 0.608 0.400 0.866 26 -0.170 .913 H4CM 0.542 0.783 0.558 0.766 27 -0.057 1.000 H8AS 0.408 0.733 0.525 1.107 27.5 0.000 1.000 H8AM 0.483 0.925 0.583 0.927 22.5 -0.567 .583 H8CS 0.475 0.725 0.496 0.783 22 -0.624 .583 H8CM 0.458 0.833 0.575 0.858 26 -0.170 .913 Stimuli Legend: L low luminance, H high luminance, 4 spatial frequency of 4 c/d, 8 spatial frequency of 8 c/d, A achromatic white/black gratings, C coloured red/black gratings, S stationary 0c/s and M moving at 4 c/s.
Chapter 6: Taq1 allele of the DRD2 dopamine receptor gene, binocular rivalry, visual backward masking and Benton’s Judgment of Line Orientation 201
Table 6.3: Binocular rivalry rates recorded by A1+ and A1- participants using binocular rivalry tasks with high and low strength stimuli, magnocellular and parvocellular biased stimuli and the Necker Cube
Schizophrenia
A1+ Allele A1- Allele
(n = 6 ) (n = 11 )
Median Range Median Range U Z p
High Strength
BR task 0.300 0.092 0.304 0.25 8.5 -1.524 .132
Low Strength
BR task 0.217 0.092 0.263 0.425 24.5 -0.856 .404
Magno BR task 0.242 0.059 0.288 0.25 15.5 -1.764 .078#
Parvo BR Task 0.120 0.028 0.200 0.308 30.5 -0.252 .808
Necker Cube 0.217 0.187 0.367 0.275 23 -0.472 .689
Controls
A1+ Allele A1- Allele
(n = 7) (n = 17)
Median Range Median Range U Z p
High Strength
BR task 0.530 0.608 0.508 0.725 26 -0.170 .913
Low Strength
BR task 0.425 0.880 0.575 0.858 57.5 -0.127 .901
Magno BR task 0.458 0.875 0.492 0.916 54.5 -0.318 .757
Parvo BR Task 0.267 0.583 0.369 0.542 48 -0.731 .494
Necker Cube 0.288 0.284 0.258 0.300 37 -0.176 .898
Note. # indicates p <.1 significance (trend)
202Chapter 6: Taq1 allele of the DRD2 dopamine receptor gene, binocular rivalry, visual backward masking and Benton’s Judgment of Line Orientation
Table 6.4: Correct scores in backward masking tasks that bias magnocellular and parvocellular visual pathways at 4 inter-stimulus intervals (ISI) recorded by A1+ and A1- participants with schizophrenia
A1+ Allele (n=4) A1- Allele (n=8)
Median Range MedianRange U Z p
Magnocellular VBM Task
ISI 27msec 8 8 7.5 12 8.5 -1.299 .194
ISI 53msec 8 9 7 11 10.5 -0.954 .340
ISI 107msec 9.5 11 6.5 11 11.5 -0.767 .443
ISI 213msec 13 15 10.5 14 13.5 -0.429 .668
Parvocellular VBM Task
ISI 27msec 6.5 2 7 8 11 -0.860 .390
ISI 53msec 9 7 8.5 10 15 -0.171 .864
ISI 107msec 12 8 10 14 12.5 -0.600 .549
ISI 213msec 13 9 12.5 10 14 -0.342 .732
In the control group, there were no differences in the error scores for Lines 1,
5, 6, 7 and 11 (Figure 5.2 b). Line error scores failed to reach statistical significance in this group (see Appendix 5 for results). When total line error scores for all participants (those with schizophrenia and healthy controls) were combined the significant difference detected in line 10 between the alleles was preserved (M =1.1,
SD = 1.4 compared to M = 0.5, SD = 1.4; χ2 [1, 5] =14.583, p = .012). No other significant differences were found.
Berman et al., (2003) observed a gender effect where girls carrying the A1+ allele had lower visuospatial functioning than that of boys with the A1+ allele.
Gender differences were not accounted for in the present study. In Berman’s study
Chapter 6: Taq1 allele of the DRD2 dopamine receptor gene, binocular rivalry, visual backward masking and Benton’s Judgment of Line Orientation 203
the group of participants with schizophrenia comprised 15 males and three females, and the control group comprised seven males and 13 females.
6.5 Discussion
In the samples reported here the proportion of A1+ to A1- participants with schizophrenia were similar to those of control participants. Previous research has reported that the A1+ status is over represented in patients with schizophrenia based on post mortem studies (Noble, 2000; Noble, 2003). Equally, a lack of association between the Taq1A allele of the DRD2 receptor and schizophrenia has been reported in previous studies (Behravan et al., 2008; Kishuda et al,. 2003; Ohara et al., 1996;
Parson et al., 2007; Suzuki, Kondo et al., 2000). This lack of association suggests that differences noted in performance on binocular rivalry, backward masking and
BJLO tasks may not be associated with the presence A1 allele of the DRD2 gene in schizophrenia per se.
It has been reported that A1+ individuals generally have more symptoms of schizophrenia (Ohara et al., 1996; Sanjuan et al., 2004) than those with A1- Status and are at greater risk of significant side effects (Alenius et al., 2008; Kaiser et al.,
2002) and tend to have more favourable responses to medication that block D2 receptors (Scharfetter, 2004; Suzuki, Mihara et al., 2000). Those with schizophrenia with A1+ status receiving anti-psychotic medication, which is considered to be an index of dopamine D2 receptor blockade (Cotes et al., 1977; Gruen, 1978; Seeman,
2002), also have higher serum prolactin levels, than those with A1- status.
204Chapter 6: Taq1 allele of the DRD2 dopamine receptor gene, binocular rivalry, visual backward masking and Benton’s Judgment of Line Orientation
Table 6.5: Correct scores in backward masking tasks that bias magnocellular and parvocellular visual pathways at 4 inter-stimulus intervals (ISI) recorded by A1+ and A1- control participants
A1+ Allele (n=4) A1- Allele (n=10)
Median Range Median Range U Z p
Magnocellular VBM Task
ISI 27msec 9 6 8 11 14.5 -0.784 .433
ISI 53msec 13.5 8 8.5 11 11 -1.287 .198
ISI 107msec 14.5 8 12 11 15.5 -0.645 .519
ISI 213msec 14.5 8 13.5 9 15.5 -0.648 .517
Parvocellular VBM Task
ISI 27msec 10.5 5 10.5 5 18.5 -0.219 .826
ISI 53msec 13.5 6 11 5 9 -1.578 .114
ISI 107msec 13.5 3 13 9 20 0.000 1.000
ISI 213msec 13 4 12 8 11 -1.290 .197
Studies in individuals with schizophrenia that utilise spatial, temporal, and contrast sensitivities known to be mediated by dopamine and dopamine receptors, indicate that dopamine-related abnormalities originating in the primary visual pathway contribute to abnormalities detected at higher levels of visual processing in schizophrenia (Chen, Levy et al., 2003; Harris et al., 1990; Keri, Antal et al., 2002;
Keri, Janka et al., 2002; Masson et al., 1993; Schwartz et al., 1988; Schwartz 1990;
Shermata & Chen, 2004; Slaghuis, 1998; Slaghuis & Curran, 1999).
Chapter 6: Taq1 allele of the DRD2 dopamine receptor gene, binocular rivalry, visual backward masking and Benton’s Judgment of Line Orientation 205
Schizophrenia by Allele
4
3 * 2
BJLO Line Errors BJLO Line 1
0 L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11
A1+ (n=6) A1- (n=12) a.
Healthy Controls by Allele
4
3
2
1 BJLO Line Errors Line BJLO
0 L1 L2 L3 L4 L5 L6 L7 L8 L9 L10 L11
A1+ (n=8) A1- (n=12) b.
Figure 6.1: Benton’s Judgement of Line Orientation (BJLO) line error scores according to the presence of the A1 allele in subjects with (a) schizophrenia and (b) healthy controls.
Note: * p < .05. Error bars indicate standard error.
Animal models suggest that density and frequency of D2 dopamine receptors found in the retina and primary visual pathway are similar to those in the primate striate cortex (Djamgoz et al., 1997; Schorderet & Nowak, 1990; Witkovsky, 2004) and the genetic expression of D2 receptors in the retina reflects that of the striatum
206Chapter 6: Taq1 allele of the DRD2 dopamine receptor gene, binocular rivalry, visual backward masking and Benton’s Judgment of Line Orientation
(Stormann, Gdula, Weiner & Brann, 1990). Lower densities of D2 receptors in the retina and primary visual pathway in A1+ individuals are likely to affect temporal and luminance contrast discrimination and visuospatial processing in these individuals. Although greater concentrations of exogenous dopamine may be present in the visual pathway and striatum of individuals with schizophrenia, dopamine binding will be diminished in those who carry the A1 allele due to the lower density of D2 dopamine receptors, compared to their A1- counterparts. In the current study a trend was noted in binocular rivalry rates between A1+ and A1- participants with schizophrenia using stimuli that biased the magnocellular visual pathway. Although no other statistical differences were observed between the two groups on other binocular rivalry tasks or backward masking task, it may be speculated that this effect is related to the action of dopamine on the magnocellular or dorsal pathway, which may play a role in binocular rivalry. Replication in a larger sample may provide better insights.
The density and function of D2 receptor sites in the striatum provide the rationale for including studying this particular dopamine related gene. A1+ status has been associated with diminished dopaminergic activity in the central nervous system, as evidenced by prolonged P300 associated latency, (Noble et al., 1994), reduced visuospatial function (Berman & Noble, 1995) and reduced glucose metabolism in the brain (Noble, 1998). Thus the Taq 1A polymorphism of the
DRD2 gene may provide a useful tool to investigate dopaminergic involvement in visual processing and binocular rivalry.
Visuospatial abnormalities have previously been associated with the A1+ status
Berman & Noble, (1995), Berman & Noble, (1997), and Berman et al., (1996) found that A1+ boys made more errors than A1- boys on all eleven of the lines of the BJLO
Chapter 6: Taq1 allele of the DRD2 dopamine receptor gene, binocular rivalry, visual backward masking and Benton’s Judgment of Line Orientation 207
task, with the effect being largest on the right in most presentations. Analysis of individual lines in the current study revealed A1+ participants with schizophrenia made fewer errors on lines 3, 4, 8 and 9 than their A1- counterparts and that A1+ participants with schizophrenia made more errors on Line 10 (χ2[1, 18] =13.95, p =
.016) than those with A1- status. However, it is impossible to tell if this difference in
Line 10 of the BJLO is artefact or a real effect. The data are difficult to interpret due to the small sample size, as there are no prior comparative studies in schizophrenia where visuospatial ability is investigated in relation to line errors.
The sample size in the current study was calculated on previous data to determine if a difference in BJLO performance existed between subjects with schizophrenia versus healthy controls, rather than between the alleles. Replication in a larger sample is necessary. Future studies investigating visuospatial ability and binocular rivalry that include analyses of an array of dopamine-related genes in a larger sample may provide insights into these mechanisms.
208Chapter 6: Taq1 allele of the DRD2 dopamine receptor gene, binocular rivalry, visual backward masking and Benton’s Judgment of Line Orientation
Chapter 7: Overview, General Discussion and Conclusions
7.1 Overview and General Discussion
Binocular rivalry provides a unique opportunity to investigate visual awareness and specific elements of visual processing in schizophrenia. Theoretical models of binocular rivalry were examined in participants with schizophrenia and healthy controls using a ‘within-subject between-groups’ design. The apparatus and method of collecting binocular rivalry data (Miller et al., 2003) was able to be manipulated so that specific stimulus characteristics (luminance contrast, spatial frequency, colour, movement and stimulus strength) could be investigated.
7.1.1 Exploring binocular rivalry rate.
The first study explored the effect of stimulus characteristics on binocular rivalry data in a group of healthy participants using a 2x2x2x2 repeated measures
‘within-subject’ design. Each participant completed 16 binocular rivalry tasks, to investigate the effect that increasing luminance contrast, spatial frequency, colour and movement had on binocular rivalry rate and dominance durations. Luminance contrast and movement had a significant effect on binocular rivalry rate in this group, however large individual variations in binocular rivalry rates were observed. When participants were sorted into fast and slow alternators according to mean binocular rivalry rates across the 16 stimulus conditions, fast alternators demonstrated a greater increase in binocular rivalry rate as stimulus strength increased. These data provided general support for an oscillation model.
Slow binocular rivalry rates were observed in participants with schizophrenia using high- and low-strength binocular rivalry stimuli, extending the work of
Pettigrew and Miller (1998) and Miller et al., (2003). These results challenge the assertion that slow binocular rivalry is a trait maker for bipolar disorder (Pettigrew &
Chapter 7: Overview, General Discussion and Conclusions 209
Miller 1998; Miller et al., 2003). It may be that slow binocular rivalry rate reflects visual processing abnormalities associated with cognitive deficits in mental illness.
Significantly slower binocular rivalry rates were also observed in participants with schizophrenia compared with healthy controls in binocular rivalry stimulus conditions that biased the magnocellular and parvocellular visual pathways (p < .02 and p < .006 in the magnocellular and parvocellular binocular rivalry tasks, respectively). These results were validated against VBM tasks widely accepted to test magnocellular and parvocellular pathway processing, and to consistently separate individuals with schizophrenia from healthy participants. Significant differences in VBM performance between the groups were observed (magnocellular
VBM task p = .01; and parvocellular VBM task p < .001), with participants with schizophrenia performing more poorly on both tasks.
The suggestion that binocular rivalry is related to competition between the two cortical hemispheres was also investigated. Participants with schizophrenia performed more poorly on the BJLO task, a relatively pure visuospatial task that is processed predominately within the right cortical hemisphere, compared to healthy controls (global score, p = .002), indicating theoretical abnormal right cortical hemisphere processing. When these results were compared with binocular rivalry rates, BJLO global scores correlated with binocular rivalry rates recorded by participants with schizophrenia in the magnocellular biased condition.
7.1.2 Dominance durations.
Normalised dominance durations (time periods between button pushes, measured in milliseconds, expressed as fractions of their means), have been demonstrated to approximate a gamma-density function (Carter & Pettigrew, 2003;
Logothetis et al., 1996; Miller et al., 2003). When histograms of the normalised
Chapter 7: Overview, General Discussion and Conclusions 210
dominance durations were drawn for each task, typical right-skewed distributions resulted. However, few were able to be fitted to a gamma-density function using
Kolmogorov-Smirnov goodness-of-fit tests, making these data difficult to interpret.
As an alternative to fitting dominance durations to a theoretical gamma-density function, the distribution of dominance durations between groups were compared statistically using the Smirnov test statistic. Differences in cumulative dominance distributions for schizophrenia participants and healthy control participants (m and n respectively) were compared. Critical values, determined by w0.95 ≈1.36√ m+n/ mn
(CV-T for S), were compared to the Smirnov T (the greatest distance in values along the distribution) across all test conditions. This allowed a direct comparison to between groups in each task.
There were no differences in the cumulative dominance durations recorded by participants with schizophrenia in the low- and high-strength binocular rivalry tasks when compared to those of healthy participants. However, significant differences were observed between the groups in the tasks that used stimuli to bias magnocellular and parvocellular visual pathways. Participants with schizophrenia recorded more 0.5-second dominance durations in both conditions, but less dominance durations of 1.5 to 4 seconds compared to those recorded in control participants in the magnocellular binocular rivalry task. This increased number of shorter dominance durations recorded by participants with schizophrenia may be interpreted as reflecting abnormal magnocellular processing early in the visual pathway, while the abnormally-long dominance durations seen in participants with schizophrenia (and not healthy participants) may reflect abnormal parvocellular processing at the cortical level.
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7.2 Neurotransmission and Binocular Rivalry: Does Dopamine Have a Role?
Investigating binocular rivalry, VBM and visuospatial ability in schizophrenia, a disease associated with abnormal dopaminergic function (Hirvonen et al., 2005;
Seeman & Kapur, 2000), provides the opportunity to explore the potential role of dopamine in human subjects. Animal models provide evidence that density and frequency of D2 dopamine receptors found in the retina and primary visual pathway are similar to those in the primate striate cortex, and that D2 receptors play a major role in visuo-cognitive processes in dopamine-related conditions such as schizophrenia (Djamgoz et al., 1997; Schorderet & Nowak, 1990; Witkovsky, 2004).
General support for the notion that dopamine plays a role in binocular rivalry was provided as participants with schizophrenia consistently recorded slower binocular rivalry rates than healthy participants. Additionally, higher doses of anti- psychotic medication had an effect on binocular rivalry rates in response to higher- strength stimuli. Slow binocular rivalry rates may indicate increased dopamine release within the striatum or visual pathways. This effect may be direct or due to the stimulatory effect of serotonin on dopamine release.
It was theorised that that a genetic variation in the density and distribution of
D2 receptors in the retina and cortex (the presence of the A1 allele of the Taq 1A
DRD2 receptor gene) may account for some of the individual variation in performance in visual tasks reported here. It was hypothesised that A1+ individuals would perform more poorly on binocular rivalry, backward masking and the BJLO tasks than those with A1- status.
A trend was noted in binocular rivalry rates between A1+ and A1- participants with schizophrenia using stimuli that biased the magnocellular visual pathway (p =
.78). However, no other statistical differences were observed between the two
Chapter 7: Overview, General Discussion and Conclusions 212
groups on binocular rivalry tasks or backward-masking tasks were noted in either the group with schizophrenia or the control group. The BJLO task revealed that A1+ participants with schizophrenia made significantly more errors for line 10 than those without, but made fewer errors on lines 3, 4, 8 and 9 than their A1- counterparts.
These data are difficult to interpret and replication in larger groups is necessary.
Future studies investigating several alleles may provide more fruitful data.
7.3 Combining Theories to Produce a New Model of Binocular Rivalry
Studies have demonstrated that transient (magnocellular) channel neurons respond to the onset and offset of a stimulus 50-80 msecs before the sustained
(parvocellular) channel neuron, with the response of the sustained channel neuron dependent on the spatial frequency of the stimulus (Breitmeyer & Ganz, 1976). In the VBM paradigm it is thought that magnocellular neurons inhibit parvocellular neurons via internuncial neurons at the LGN and cortex based on their response duration. Thus, when a mask stimulus follows a target stimulus the magnocellular neurons carrying information regarding the mask interrupt the sustained parvocellular response elicited from the target stimulus at the LGN cortical junction.
Breitmeyer & Ganz, (1976) presented a model of visual masking outlined in (recall
Figure 4.7 from Chapter 4).
Chapter 7: Overview, General Discussion and Conclusions 213
T Target S
- + Mask
0 100 200 300 400 msec
Adapted from Breitmeyer, B. G. and L. Ganz (1976). "Implications of sustained and transient channels for theories of visual pattern masking, saccadic suppression, and information processing." Psychological Review 83(1): 1-36.
Figure 4.7; The time course of the transient and sustained channels when the target precedes the mask (backward masking).
Key: T = transient channel, S = sustained channels. Arrows indicate the direction of the masking interaction. A minus sign indicates that the interaction is inhibitory, and a positive sign indicates that the interaction is one of sensory integration.
According to the sustained-transient theory in VBM, if the mask and test stimuli are similar in orientation and spatial frequency, maximum masking will occur at stimulus onset synchrony. This prediction arises from the assumption that, when the mask and target are similar, equal proportions of magnocellular and parvocellular cells are stimulated and masking effects derived from ‘within channel’ inhibition; transient on transient and sustained on sustained (May et al., 1988). Breitmeyer &
Ganz (1976) postulated that transient neurons inhibited sustained neurons via internuncial neurons at the LGN and cortex based on their response duration.
Applied to binocular rivalry, it could be that the magnocellular pathway is responsible for triggering the alternation of images seen in binocular rivalry. Visual information is carried more rapidly to the cortex by monocular than binocular neurons, and both types contain magnocellular and parvocellular cells, with parvocellular neurons concentrated around the fovea, while the density of
Chapter 7: Overview, General Discussion and Conclusions 214
magnocellular neurons increases with foveal eccentricity (Livingstone & Hubel,
1987). Thus, during binocular rivalry monocular magnocellular channel neurons from one eye reach the LGN, inhibit binocular neurons carrying information from both eyes at the LGN and thus interrupt parvocellular neuronal processing in the cortex. Thus, it is the action response of the parvocellular neurons in the cortex that determine the dominance duration of the image, and thus the rate (recall Figure 4.9 from Chapter 4 below).
Figure 4.9A model of binocular rivalry with rapid magnocellular response followed by the parvocellular response to continuous stimuli (vertical and horizontal lines) in the right and left eyes respectively at corresponding retinotopic areas.
Note: Arrows indicate if the masking interaction is interruption or integration. The bottom axis denotes the fluctuating images seen during binocular rivalry over time. Note that the duration of the image is not constant.
This revised model combines the two prevailing models of binocular rivalry; the pattern rivalry model and the pathway model. The pattern model suggests binocular rivalry occurs where the conflicting stimuli presented to each eye compete
Chapter 7: Overview, General Discussion and Conclusions 215
for dominance from interactions between monocular and binocular neurons in the visual cortex (see Blake, 2001). The pathway model suggests that binocular rivalry is related to the actions of the parvocellular, magnocellular pathway processing, or both in the retina, LGN and cortex (He et al., 2005; Carlson & He, 2000; Blake et al.,
1991). This model suggests that the magnocellular pathway gates (Javitt, et al., 1999) or acts as a ‘switch’, with its rapid response to local visual information ‘turning off’ or interrupting cortical processing the parvocellular neurons in the cortex derived from parvocellular neurons located in corresponding retinal location in the opposite eye.
7.4 Slower Binocular Rivalry and Visual Processing in Schizophrenia
The use of binocular rivalry enables questions regarding perceptual selection and unconscious processing to be addressed experimentally (Carmel, Arcaro,
Kastners & Hasson, 2010). Binocular rivalry is a task that provides an objective behavioural measure of the temporal characteristics of neural processes within the visual system. The binocular rivalry stimuli can be manipulated to access specific aspects of the visual system known to be abnormal in schizophrenia. Previous studies have identified that individuals with schizophrenia have deficits when processing low-luminance, temporally-modulated stimuli and abnormal processing in the magnocellular pathway (Green et al., 2009). Using binocular rivalry to examine visual processes in schizophrenia can be achieved by exploiting visual anomalies known to exist in schizophrenia. Here, it has been demonstrated that individuals with schizophrenia consistently record slow rates binocular rivalry alternations. Slow binocular rivalry in schizophrenia may indicate slow processing of visual information at a number of stages along the visual pathways that may contribute to
Chapter 7: Overview, General Discussion and Conclusions 216
higher-order cognitive deficits in working memory, executive functioning and attention (Martinez et al., 2008).
Investigating binocular rivalry in schizophrenia using stimuli to bias the magnocellular and parvocellular visual pathways adds to a large body of research undertaken in schizophrenia. Using tasks that selectively bias the parvocellular and magnocellular systems to study schizophrenia is an approach that has been endorsed by the CNTRICS (Green et al., 2009). Applying the above model to the schizophrenia binocular rivalry data provided in this study indicates that the perceptual abnormalities associated with schizophrenia are likely to be due to abnormalities in parvocellular and magnocellular pathway processing, or in the retina, LGN and cortex. An over-active magnocellular pathway, with its rapid response to local visual information from the retina to the LGN, interrupts or gates cortical processing of the parvocellular neurons in the cortex. Individuals with schizophrenia may therefore be creating ‘false’ or ‘incorrect’ visual images and be misinterpreting visual information contributing to paranoia and perceptual disturbances commonly experienced in this illness. Binocular rivalry may be able to provide new insights into the neural mechanisms involved in mental illness.
7.5 Limitations
It is not possible to be completely confident in the magnocellular and parvocellular binocular rivalry tasks access the magnocellular and parvocellular visual pathways. Although every effort was made to use stimulus parameters that biased either the magnocellular or parvocellular pathway, it is acknowledged that there is considerable overlap in the pathways (Ellemberg, Hammarrenger, Lepore,
Roy & Guilemot, 2001). The sensitivity of magnocellular neurons is lower than parvocellular neurons at higher spatial frequency. Allowing free eye movements that
Chapter 7: Overview, General Discussion and Conclusions 217
generate transients during binocular rivalry tasks introduces the possibility of a response by magnocellular neurons in the parvocellular BR task. There is much debate in the current literature regarding the degree of separation that can be achieved by manipulating stimulus parameters (see Skottun & Skoyles, 2011).
Kuo, Schmid and Atchison (2011) suggest that the degree to which a low contrast location task such as the Magnocellular VBM task used in this study creates bias toward magnocellular processing is unclear. Lesions studies indicate damage to the parvocellular system in the parvocellular layer of the LGN result greater contrast sensitivity losses than leisions in the magnocellular layer (Skutton & Skoyles, 2011).
However it should be noted that although both pathways may be activated, manipulations of the lumiance and spatial contrast vary the relative balance of the activation to effectively bias either the magnocellular or parvocellular proccessing.
The resolution and refresh rates of the computer presentation screen also limited the extent that luminance contrast and temporal frequency could be altered in the binocular rivalry tasks, and luminance and ISI could be altered in the backward masking task. This was an issue particularly for the magnocellular binocular rivalry task and the magnocellular backward masking tasks. To be confident that adequate separation between parvocellular and magnocellular pathways was achieved a more sophisticated presentation monitor would need to be employed. Due to the financial constraints of the project the available computer monitor was adopted as it adequately biased the magnocellular and parvocellular pathways to allow sufficient investigation of the pathways.
Reporting of perceptual alternation by pressing keys on a computer key pad during the binocular rivalry task relies on the participant accurately reporting changes in perception. It has been observed that in humans recognition of an object
Chapter 7: Overview, General Discussion and Conclusions 218
generally occurs around 180msec with motor responses intiated from 540-720msec
(Castelo-Branco, Neuenschwander & Singer, 1998). It is possible that participants who experience quicker perceptual alternations during binocular rivalry may not have sufficient time to respond pressing a response key before the opposing image becomes dominant. It possible that the slow binocular rivlary rate observed in particpants with schizophrenia reflects slower reaction time rather than slower alternation rate. This is unlikely, as particpants verbal reports during practice sessions matched their key repsonses. However future studies may eliminate this uncertainity by employing a task that assesses how well each participant responds to known stimuli. For example Carter et al., (2007) employed ‘rivalry pre-test catch trials’, where a ‘movie’ of perceptual alternations was played to assess accuracy of responses and response time for each individual before they commenced the binocular rivalry task.
All tasks used in this study required participants to attend to the task and some level of concentration. However ‘attention’ was not controlled for in this study.
Deficits related to attention have been reported in individuals with schizophrenia
(Saccuzzo et al., 1996). It is possible that attention impacted on the performance in
VBM and BJLO tasks, and to a lesser degree the binocular rivalry tasks (which are thought by many to be a perceptual task, or a pre-attentive task). Although every effort to was made to ensure that participants attended to each task, and recorded reliable data, the addition of a test to measure attention (for example the Span of
Attention Task, Kay & Sing, 1974), may have improved the study. Future studies should control for attention.
Participants with schizophrenia were not well matched to controls with respect to age and gender. An age effect was noted with respect to luminance contrast in
Chapter 7: Overview, General Discussion and Conclusions 219
binocular rivalry in controls the second chapter. The effect that age has on luminance contrast is well established in the vision literature, so the results reported in Chapter 2 were not unexpected. Although age was not strictly controlled, and some effects noted, this was minimised by only a small variation in mean ages between the two groups.
With respect to gender, males out-numbered females in the group of participants with schizophrenia while in the control group females’ out- numbered males. Although no gender differences noted in binocular rivalry rates in the first two studies; it was noted in Chapter 4 that female controls recorded faster binocular rivalry rates than males in both magnocellular and parvocellular tasks. This is consistent with a small number of reports that that indicate females record faster binocular rivalry rates than males (Cogan, 1973; Goldstein & Cofoid, 1965). No studies report males record faster binocular rivalry rates. However, it was noted in
Chapter 4 that females with schizophrenia recorded slower binocular rivalry rates than their male counterparts on the binocular rivalry task that biased the magnocellular pathway, but no differently to males on the parvocellular biased task.
This effect has not been previous reported.
It is possible that the gender-related differences in binocular rivalry observed here are due to hormonal changes associated with the menstrual cycle. Hormonal changes, and the use of oral contraceptives, have been linked to alterations in retinal function and sensitivity changes in some women (Eisner et al., 2004). The actions of oestrogen and progesterone may contribute to improved colour vision performance at ovulation (Giuffre et al., 2007), increases in visual sensitivity during menstruation
(Barris et al., 1980) and decreases in pattern reversal evoked potentials (Yilmaz et al., 1998). Hormonal alterations are not the same for all visual pathways, and
Chapter 7: Overview, General Discussion and Conclusions 220
pronounced individual differences with individual’s visual adaptation capabilities vary substantially over periods of weeks (Eisner et al., 2004). If the binocular rivalry task is sensitive to these changes future studies should match participants with respect to gender and in female participants control for menstrual cycle variations or use of the contraceptive pill when luminance contrast and colour are measured.
It is important to note, that the gender effect noted in the first study reported in
Chapter 4 was not replicated in the second study in Chapter 4 where binocular rivalry rates reported from rivalry tasks that biased the magnocellular and parvocellular pathway were compared with magnocellular and parvocellular biased VBM. The gender effect reported in the first may therefore be an artefact.
It is possible that the slower rate observed in participants with schizophrenia may be related to medication. All participants with schizophrenia were relatively symptom free at the time of testing largely due to the fact they were receiving adequate doses of antipsychotic medication to treat their symptoms. In Chapter 3, a medication effect was observed in the high-strength binocular rivalry task.
Participants taking lower doses of anti-psychotic medications recorded faster binocular rivalry rates. However no difference was observed in the low strength condition. No medication effects were observed in either the magnocellular and parvocellular binocular rivalry task reported in Chapter 4. Similarly there was no medication effect on BJLO scores in participants with schizophrenia in Chapter 5.
These results are consistent with other studies reporting no medication effect on
BJLO performance (Buchanan et al., 1994; Halari et al., 1994; Riley et al., 2000).
In this study, participants with schizophrenia were taking a variety antipsychotic medication. To enable comparisons doses of antipsychotic medication were converted to chlorpromazine equivalents (CPZE) and then categorised into high
Chapter 7: Overview, General Discussion and Conclusions 221
and low by median split. Although the conversion of antipsychotic doses into
CPZE’s is generally accepted and widely practiced in schizophrenia research
(Centorrino et al., 2002; Hargreaves et al., 1987; Humberstonse et al., 2004; Owen et al., 2002; Woods, 2003), it is acknowledged that these comparisons may be inaccurate. Many newer antipsychotic medications have been compared in comparative clinic trials with haloperidol and then converted to CPZE’s; 2mg
Haloperidol being comparative to 100mg Chlorpromazine (Wood, 2003).
The effect that dopamine and dopamine antagonists (antipsychotic medications) on binocular rivalry is currently unknown. The observed effect of other neurotransmitters suggests that dopamine has an effect on binocular rivalry.
Serotoninergic 5HT1A and 5HT2A agonist have been observed to decreases binocular rivalry rate in a dose-dependent manner, (Carter et al., 2005; Frecska
White, et al., 2003) while Gamma-aminobutyric acid (GABA), is thought to be involved in binocular rivalry, via suppression of dLGN inter-neurons (Bickford, et al., 2008). Agents such as ethanol (Donnelly & Miller, 1995), sodium amytal and caffeine have been observed to influence binocular rivalry rate in control participants providing some suggestive evidence of a dopamine effect. The results presented in this study are also suggestive of a dopamine effect. However due to the explorative nature of this study and the many logistical and ethical issues surrounding the collection of data from un-medicated participants with schizophrenia, a thorough investigation of the role of dopamine and the effect of specific antipsychotics on binocular rivalry was beyond the scope of this study. These issues require further investigation in future studies.
Chapter 7: Overview, General Discussion and Conclusions 222
7.6 Implications for Future Research
Although classical binocular rivalry does not appear sensitive enough to separate individuals with schizophrenia from controls, it may be appropriate to include a binocular rivalry task that biases the magnocellular and parvocellular pathways in a battery of tests to aid the early detection of psychosis and schizophrenia. Despite many years of research into schizophrenia, no single causative factor has been determined. It is conceivable that schizophrenia is not a disease that affects specific cortical areas or neural pathways, but a disease associated with the integration of a number of neural processes, particularly the integration of perceptual information into higher-order cognitions. Gains in future research may be made by incorporating binocular rivalry methodologies with fMRI and VEP technologies to investigate how visual information is integrated along the visual pathway. A study utilising binocular rivalry and fMRI or VEPs may be particularly useful to target the transfer of information in the thalamus, which is often considered the transfer station of all cortical information.
Carefully designed binocular rivalry tasks combined with a battery of cognitive tasks may provide unexplored insights into the visual aspects to cognitive processing.
Although cognitive deficits in schizophrenia are relatively stable over time (Gold,
2004), they are relatively independent of the symptomatic manifestations of the illness (Gold, 2004; Heinrichs & Zakzanis, 1998). Future studies that compare perceptual alternation rates during periods of illness (when a participant display marked psychotic symptoms) with symptoms free periods may provide some insights into the cognitive decline associated with schizophrenia.
The binocular rivalry task provides a unique opportunity to investigate visual awareness in schizophrenia as manipulations can be made to the stimulus
Chapter 7: Overview, General Discussion and Conclusions 223
characteristics to investigate specific components of the visual system without the participant being aware. Adjustments to stimulus parameters in this study were observed to effected binocular rivalry rate and dominance durations in participants with schizophrenia and controls. It was noted that stimuli that biased the magnocellular pathway slowed the binocular rivalry rate in controls to a greater extent than in participants with schizophrenia. These data provide a platform on which to base further research that are consistent with the recommendations from the third meeting of the CNTRICS (Green et al., 2009).
Manipulations to the binocular rivalry task may also allow research to be undertaken into neurotransmitter involvement in schizophrenia and other mental illnesses. Testing samples of subjects with a variety of mental illnesses on and off antipsychotic medications may advance what is known about neurotransmitter involvement in binocular rivalry and visual information processing. There have been many advances made in vision research utilising studies in Parkinson’s disease in to explore the role of dopamine in retinal functioning, spatial and luminance contrast
(Bodis-Wollner, 2003; Harris et al., 1992; Haug, Trenkwalder, Arden & Paulus,
1994). Including participants with Parkinson’s disease both on and off dopamine agonist medication may therefore provide valuable insights into binocular rivalry.
Furthermore, investigating the role of dopamine along with other neurotransmitters such as GABA and glutamate in vision by including a binocular rivalry tasks may provide new methods of investigating neurotransmitter involvement and the effect of medication in visual processing in schizophrenia and other mental illnesses.
In this study a single allele for the DRD2 receptor gene was utilised to investigate large individual and group differences in binocular rivalry rates observed in this study and poorer performance on visuospatial tasks in this study in
Chapter 7: Overview, General Discussion and Conclusions 224
participants with schizophrenia compared to controls. Although the results did not provided conclusive evidence that the Taq1A dopamine gene for the DRD2 receptor accounted for differences in visual processing, the role of dopamine was implicated.
Future studies that incorporate imagining studies with genetic studies may integrate the basic biology with the disease mechanisms associated with schizophrenia.
Gene’s related to prefrontal brain functions associated with working memory and executive function implicate genetic variation in dopaminergic systems. Genetic variations in the dopaminergic system for example Catechol-O-methyl tranferase
(COMT) and downstream signalling molecules such as V-akt murine thymoma viral oncogene homologue 1 (AKT1) repeatedly associated with schizophrenia (Mathur,
Law, Megson, Shaw & Wei, 2010; Tan, Callicott &Weinberger, 2009) may prove useful sites for future binocular rivalry studies. Studies that include analyses of an array of genes in a larger sample of healthy participants and participants with schizophrenia may enable researchers to investigate aspects of visual processing currently not investigated in the literature.
7.7 Conclusion
The research contributes empirical data and adds to what is known about binocular rivalry in schizophrenia. Consistently slower binocular rivalry rates were observed in participants with schizophrenia, indicating abnormally-slow visual processing in this group. These data support previous studies reporting visual processing abnormalities in schizophrenia and suggest that a slow binocular rivalry rate is not a feature specific to bipolar disorder, but may be a feature of psychosis in general.
Although the mechanisms of binocular rivalry remain unexplained, this research provides a platform on which to base future studies. Binocular rivalry like
Chapter 7: Overview, General Discussion and Conclusions 225
psychosis is an internal perceptual phenomenon experienced by the individual. The only outward sign that the phenomena is occurring is the verbal or other report of person’s visual experience. An objective behavioural measure of internal perceptions allows the locus of awareness, perceptual selection and unconscious processing (Carmel, Arcaro, Kastners & Hasson, 2010) to be investigated in schizophrenia. Carefully designed binocular rivalry tasks combined with a battery of cognitive tasks may provide unexplored insights into the visual aspects to cognitive processing in schizophrenia.
The contributions of the magnocellular or dorsal pathways and parvocellular or ventral pathways to binocular rivalry, and therefore to perceptual awareness, provide a rich area of research. Slow binocular rivalry rates, recorded by participants with schizophrenia when the stimuli biased the magnocellular and parvocellular visual pathways, correlated with poorer performance on VBM tasks effective in separating those with schizophrenia from controls. These data supported an alternative model of binocular rivalry based on VBM theory. This alternative model suggests that the magnocellular (or dorsal system) initiates perceptual awareness of an image and the parvocellular (or ventral system) maintains the perception of the image, making it available to higher cortical processing occurring within the cortical hemispheres.
Thus abnormalities in both the magnocellular and parvocellular pathways contribute to perceptual disturbances that ultimately contribute to the cognitive dysfunction associated with schizophrenia. Combining binocular rivalry tasks that bias magnocellular and parvocellular pathways with fMRI or VEPs methodologies in future research in schizophrenia may further advance what is currently known about the fluctuating course and cognitive decline associated with the disorder.
Chapter 7: Overview, General Discussion and Conclusions 226
Although this research was limited in terms of age and gender matching the use of a within-subject between-group design provides some confidence in the results not currently available in the literature. The results reported in the current study raise a number of interesting questions that can be investigated in future studies. As discussed, the group of participants with schizophrenia in this study was limited to an out patient population with a relatively narrow range of presenting psychotic symptoms, who all receiving therapeutic doses of antipsychotic medications. Future studies that expand to sample population to include individuals with a number a greater range of symptom profiles that include deficits associated with spatial memory and executive functioning may allow further investigation into cognitive processing in schizophrenia and other mental illnesses. The effect of the illness and long term use of antipsychotic medication is yet to be determined in binocular rivalry. Testing participants with schizophrenia using binocular rivalry tasks during periods of illness and remission both on and off antipsychotic medication may unlock some of the complex issues related to dopamine functioning within the visual system provide some insights into the fluctuating course of the disorder.
Chapter 7: Overview, General Discussion and Conclusions 227
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APPENDICES
Appendix A: Backward Masking Task Instructions for Parvocellular VBM Task
For this task you are asked to identify which of four target letters, a capital A, T, V or Y, appears in the centre of the screen by pushing the corresponding letters on a computer keyboard. Each letter is presented for a very short time and is followed by a mask or a distracting letter, the letter S, which makes the task more difficult.
You will first see a green screen on the computer monitor. You will then hear a short beep and a cross will appear at the centre of the screen.
+
This cross represents where the red target letters will appear. You are asked to look at the cross until the red target letter is presented on the screen. The target letter will be either capital A, T, V or Y.
A
A very short time after the target letter appears a mask letter appears. This is the letter S. This letter S should be ignored.
S
The next screen is the response screen. This screen asks you to ‘Select A T V Y’.
Select A T V Y
Appendices
When this appears on the screen you are asked to record which letter (A T V or Y) appeared before the S, by pushing the corresponding letter on the computer keyboard. If you are unsure you are asked to guess. The task is designed so that most people get some wrong.
Once you have selected your response on the computer keyboard, a blank green screen will appear and then the process is repeated.
First you will hear a beep, then the cross will appear in the centre of the screen, then the target letter (A T V Y) will appear in the centre of the screen followed by the mask (the letter S) in the same location and then the screen that asks you to select your response appears. The process is repeated for 64 trials.
Appendices 297
Appendix B: Backward Masking Task Instructions for Magnocellular Visual Backward Masking (VBM) Task
For this task a letter (A, T, V or Y) can appear in one of four locations, up, down, left or right. You are asked to record where you think the letters appear on the screen by pushing the arrow keys on a computer keyboard. Each letter is presented for a very short time and is followed by a mask, which consists of the letter S presented in all four possible locations which makes the task more difficult.
You will first see a grey screen on the computer monitor. You will then hear a short beep and a cross will appear at the centre of the screen.
+
This cross marks the centre of the screen. You are asked to look at the cross until the grey target letters either to the right or to the left, or up or down of the centre of the screen. The target letter will be either capital A, T, V or Y.
A
A very short time after the target letter appears a mask appears, which consists of four letter S’s appearing in all four possible locations. These four S’s should be ignored.
S
SS
S
The next screen is the response screen. This screen has four arrows on it representing the four possible positions of the target letter.
Appendices
When this appears on the screen you are asked to record where the target letter appeared, by pushing the arrow keys on the computer keyboard. If you are unsure you are asked to guess. The task is designed so that most people get some wrong.
Once you have selected your response on the computer keyboard, a blank grey screen will appear and the process is repeated for 64 trials.
First you will hear a beep, then the cross will appear in the centre of the screen, then the target letter (A T V Y) will appear in one of four locations on the screen (up, down, left or right) followed by the mask (the four letter S’s, one in each of the four possible locations) and then the screen that asks you to select your response appears. Once you have responded by pushing the arrow keys the process is repeated.
Appendices 299
Appendix C: Effect of Schizophrenia Characteristics on Visual Backward Masking (VBM) Tasks
Table A: Dose level had a significant effect on visual backward masking performance at 27msec inter-stimulus interval, and DSM-IV diagnosis had significant effects at 27 and 53 msec Dose levels (CPZE) Magnocellular VBM Task <425mg CPZE >425mg CPZE (n=4) (n=10) M SD M SD U Z p ISI 27msec 4.5 3.42 8.7 2.63 6 -2.030 .042* ISI 53msec 6.3 5.19 9.4 2.95 9 -1.577 .115 ISI 107msec 6.8 3.59 10.0 3.74 9 -1.559 .119 ISI 213msec 7.3 7.09 12.0 4.14 11 -1.283 .200 Parvocellular VBM Task <425mg CPZE >425mg CPZE (n=4) (n=10) M SD M SD U Z p ISI 27msec 8.3 2.63 7.1 2.73 15 -0.713 .476 ISI 53msec 7.0 4.24 9.2 2.94 15 -0.716 .474 ISI 107msec 8.0 5.94 10.6 3.53 14 -0.855 .392 ISI 213msec 11.0 5.77 12.7 2.58 19 -0.143 .887
DSM-IV diagnosis – SCID Magnocellular VBM Task Undifferentiat Paranoid ed (n=5) (n=9) M SD M SD U Z p ISI 27msec 10.4 2.61 5.9 2.62 3 -2.665 .008* ISI 53msec 11.4 3.65 6.9 2.93 7 -2.094 .036* ISI 107msec 11.0 4.00 8.0 3.57 11.5 -1.470 .142 ISI 213msec 13.8 2.59 8.9 5.75 10.5 -1.612 .107
Parvocellular VBM Task Undifferentiat Paranoid ed (n=5) (n=9) M SD M SD U Z p ISI 27msec 7.8 4.15 7.2 1.64 22 -0.067 .946 ISI 53msec 9.0 3.61 8.3 3.39 21.5 -0.135 .893 ISI 107msec 10.8 4.09 9.3 4.53 17 -0.739 .460 ISI 213msec 13.8 1.64 11.3 4.15 16 -0.874 .382
Appendices
Positive versus Negative Symptoms of Schizophrenia (PANSS) Magnocellular VBM Task Positive Negative (n=4) (n=8) M SD M SD U Z p ISI 27msec 8.5 1.73 7.5 4.24 12 -0.706 .480 ISI 53msec 8.8 2.87 9.1 4.42 14.5 -0.257 .797 ISI 107msec 8.0 3.56 10.0 4.41 12.5 -0.595 .552 ISI 213msec 10.5 4.12 10.6 6.72 13 -0.516 .606 Parvocellular VBM Task Positive Negative (n=4) (n=8) M SD M SD U Z p ISI 27msec 8.3 3.40 6.6 2.45 11 -0.858 .391 ISI 53msec 10.8 2.75 7.1 3.40 7.5 -1.456 .145 ISI 107msec 11.3 0.96 9.0 5.61 15 -0.171 .864 ISI 213msec 12.0 2.94 11.9 4.26 14 -0.342 .732
Appendices 301
Appendix D: Score Sheet - Benton’s Judgment of Line Orientation (BJLO) Date ………………………. Participant Type of Line Error - Ska et al (1990) Benton (1978) Line 1 Line 2 Correct? Line 1 Line 2 Figure 1 Y N V H HV N R 6 11 Figure 2 Y N H QO QO1 QO2 IQOH R R 9 11 Figure 3 Y N QO1 QO2 QO3 QO4 IQO L R 4 7 Figure 4 Y N H QO QO1 QO2 IQOH L R 1 7 Figure 5 Y N H QO QO1 QO2 IQOH L R 5 11 Figure 6 Y N QO1 QO2 QO3 QO4 IQO IQO L R 2 8 Figure 7 Y N H QO QO1 QO2 IQOH L L 1 3 Figure 8 Y N QO1 QO2 QO3 QO4 IQO IQO L R 5 8 Figure 9 Y N QO1 QO2 QO3 QO4 IQO IQO L R 3 10 Figure 10 Y N H QO QO1 QO2 IQOH R R 7 11 Figure 11 Y N V Q0 QO1 QO2 IQOV L N 3 6 Figure 12 Y N QO1 QO2 QO3 QO4 IQO IQO L R 4 10 Figure 13 Y N V Q0 QO1 QO2 IQOV N R 6 8 Figure 14 Y N Q0 QO1 QO2 QO3 QO4 R R 8 10 Figure 15 Y N QO1 QO2 QO3 QO4 IQO IQO L R 2 9 Figure 16 Y N QO1 QO2 QO3 QO4 IQO IQO L R 3 8 Figure 17 Y N Q0 QO1 QO2 QO3 QO4 L L 4 5 Figure 18 Y N H QO QO1 QO2 IQOH L L 1 5 Figure 19 Y N V Q0 QO1 QO2 IQOV N R 6 10 Figure 20 Y N H QO QO1 QO2 IQOH L R 2 11 Figure 21 Y N H QO QO1 QO2 IQOH L R 1 10 Figure 22 Y N Q0 QO1 QO2 QO3 QO4 L L 2 5 Figure 23 Y N V H HV L N 1 6 Figure 24 Y N QO1 QO2 QO3 QO4 IQO IQO L R 2 7 Figure 25 Y N Q0 QO1 QO2 QO3 QO4 L R 4 9 Figure 26 Y N QO1 QO2 QO3 QO4 IQO IQO L R 7 10 Figure 27 Y N V Q0 QO1 QO2 IQOV L N 4 6 Figure 28 Y N Q0 QO1 QO2 QO3 QO4 R R 8 9 Figure 29 Y N Q0 QO1 QO2 QO3 QO4 L L 2 3 Figure 30 Y N Q0 QO1 QO2 QO3 QO4 R R 8 9
Appendices
Ska (1990) Scores Berman and Noble (1995) Scores QO Line Error Score /60 Line1 QO1 Left Hemi-space Line2 QO2 Right Hemi-space Line3 QO3 Line4 QO4 Benton (1978) Line5 V Global Score /30 Line6 H Line7 VH Line8 IQO Line9 IQOV Line10 IQOH Line11 Legend QO Intraqadrant oblique error - an error between lines from the same quadrant. QO1 An oblique confused with another oblique different by only one spacing of 18 degrees QO2 An oblique confused with another oblique different by two or three spacings of 18 degrees QO3 Both Oblique lines displaced by one or two spacings in the same direction respecting the initial spacing QO4 Both oblique lines displaced without maintaining the initial spacing V A vertical error involving an incorrect identification of the vertical line numbered 6 H A horizontal error involving an incorrect identification of the horizontal lines numbered 1 or 11 VH A vertical and horizontal error involving the simultaneous incorrect identification of the vertical and one horizontal line IQO Intraquadrant oblique errors involving the displacement of one line from quadrant to another quadrant IQOV Combined oblique interquadrant and vertical error involving the incorrect answer in combination (V + IQO) IQOH Combined oblique interquadrant and horizontal error involving the incorrect answer in combination (H + IQO) L Left hemi-space error R Right hemi-space error N Neutral position F Spatial error that relates to line closest to centre of object (proximal errors) M spatial error that relates to line in the middle of object B Spatial error that relates to line furthest from centre of object (distal errors)
Note * Participants scores are entered into the second and third columns (Line1 and Line 2). If the answer is incorrect this indicated by circling N in the third column. The researcher then indicates what type of error with respect to spacing by circling one of the error types in the 4th column (type of line error). Whether error occurred in the left or right hemi-space and the line numbers are indicated by circling the appropriate answers in the remaining columns. The number of circled responses collated in the table at the bottom of the score sheet.
Appendices 303
Appendix E. Benton Judgment of Line Orientation (BJLO) Performance Scores in Participants with Schizophrenia and Healthy Controls by A1 Allele of the DRD2 Receptor Gene.
Schizophrenia A1 (n=6) A2 (n=12) M SD M SD χ2 p Benton (30) 19.0 7.9 19.7 4.9 15 .182 Berman (60) 45.2 11.9 47.1 8.7 18 .158 Left hemifield 6.5 6.1 5.7 2.9 15 .059 Right hemifield 8.2 5.7 6.9 4.9 12.375 .336 Line1 0.7 1.6 0.0 0.0 2.118 .146 Line 2 1.2 1.6 1.0 1.7 3.15 .533 Line 3 1.7 1.9 1.9 1.3 3.15 .533 Line 4 1.7 1.4 2.2 0.9 6.171 .187 Line 5 0.8 1.2 0.5 0.5 2.25 .325 Line 6 0.2 0.4 0.2 0.6 2.531 .282 Line 7 1.7 1.6 0.5 1.0 3.886 .422 Line 8 2.3 1.5 3.1 2.2 6 .423 Line 9 2.0 1.7 2.2 1.6 8.625 .125 Line 10 2.0 1.7 1.0 2.0 13.95 .016* Line 11 0.7 1.2 0.3 0.5 2.163 .339 QO1 5.5 3.4 7.2 2.4 12.75 .174 QO2 1.0 1.3 0.8 1.5 2.932 .569 QO3 2.0 2.4 1.1 1.4 5.571 .35 QO4 1.5 1.5 0.7 2.0 8.25 .083 V 0.0 0.0 0.0 0.0 0 H 0.5 0.8 0.2 0.4 2.143 .343 VH 0.0 0.0 0.0 0.0 0 IQO 0.2 0.4 0.6 2.0 2.531 .282 IQOV 0.0 0.0 0.2 0.6 0.529 .467 IQOH 0.3 0.8 0.0 0.0 2.118 .146
Appendices
Controls A1 (n=8) A2 (n=12) M SD M SD χ2 p Benton (30) 25.8 2.2 24.8 2.7 4.722 .787 Berman (60) 55.6 2.1 54.0 3.2 12.708 .176 Left hemifield 1.8 1.2 2.8 1.7 7.778 .169 Right hemifield 2.8 1.5 3.3 2.3 3.681 .72 Line 1 0.0 0.0 0.0 0.0 Line 2 0.1 0.4 0.3 0.5 1.111 .292 Line 3 0.8 0.9 0.7 0.8 0.278 .87 Line 4 0.6 0.7 1.4 1.1 3.274 .351 Line 5 0.3 0.5 0.3 0.5 0 1 Line 6 0.0 0.0 0.0 0.0 Line 7 0.3 0.5 0.3 0.5 0 1 Line 8 1.1 1.4 2.1 1.4 6.954 .224 Line 9 0.8 0.7 0.9 0.9 1.711 .425 Line 10 0.4 0.5 0.1 0.3 2.552 .11 Line 11 0.1 0.4 0.1 0.3 0.093 .761 QO1 3.6 2.8 4.3 2.5 13.056 .11 QO2 0.5 1.4 0.0 0.0 1.579 .209 QO3 0.1 0.4 0.6 0.8 2.292 .318 QO4 0.0 0.0 0.2 0.4 1.481 .224 V 0.0 0.0 0.0 0.0 H 0.0 0.0 0.0 0.0 VH 0.0 0.0 0.0 0.0 IQO 0.0 0.0 0.1 0.3 0.702 .402 IQOV 0.0 0.0 0.0 0.0 IQOH 0.0 0.0 0.0 0.0
Appendices 305
All Subjects A1 (n=14) A2 (n=24) M SD M SD χ2 p Benton (30) 22.9 6.2 22.3 4.7 15.939 .386 Berman (60) 51.1 9.2 50.5 7.3 28.686 .071 Left hemifield 3.8 4.6 4.2 2.8 15.652 .11 Right hemifield 5.1 4.6 5.1 4.2 8.705 .795 Line 1 0.3 1.1 0.0 0.0 1.761 .185 Line 2 0.6 1.2 0.7 1.3 3.906 .419 Line 3 1.1 1.4 1.3 1.2 2.276 .685 Line 4 1.1 1.1 1.8 1.1 5 .287 Line 5 0.5 0.9 0.4 0.5 1.925 .382 Line 6 0.1 0.3 0.1 0.4 2.306 .316 Line 7 0.9 1.3 0.4 0.8 2.533 .639 Line 8 1.6 1.5 2.6 1.8 4.429 .619 Line 9 1.3 1.3 1.5 1.4 5.149 .398 Line 10 1.1 1.4 0.5 1.4 14.583 .012* Line 11 0.4 0.8 0.2 0.4 1.771 .413 QO1 4.4 3.1 5.8 2.8 22.385 .022* QO2 0.7 1.3 0.4 1.1 4.553 .505 QO3 0.9 1.8 0.4 1.4 6.873 .23 QO4 0.6 1.2 0.0 0.0 6.126 .19 V 0.0 0.0 0.0 0.0 H 0.2 0.6 0.1 0.3 1.765 .414 VH 0.0 0.0 0.0 0.0 IQO 0.1 0.3 0.3 1.4 0.734 .693 IQOV 0.0 0.0 0.1 0.4 0.599 .439 IQOH 0.1 0.5 0.0 0.0 1.761 .185
Appendices