Assessing language lateralisation using functional transcranial Doppler sonography A thesis submitted for the degree of Doctor of Philosophy UCL Heather Mary Payne Primary Supervisor: Mair´eadMacSweeney Secondary Supervisor: Bencie Woll I, Heather Payne confirm that the work presented in this the- sis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. 1 Acknowledgements I am extremely grateful to Mair´eadMacSweeney and Bencie Woll for their un- wavering support and guidance through these projects. Thank you Mair´ead for the extra chats, the 3pm chocolate fixes, and being an excellent role model. I am also extremely grateful to Nic Badcock for his guidance and for making my research visit to MacQuarie such an enjoyable and enriching experience. Thank you to the past and present Visual Communication Group for being wonderful mentors, collaborators, and friends. Thank you Mum and Dad for keeping me going and helping to pick me up in the trickier moments. Thank you Yotam - during the course of this work we met, married, and started our little family. You have helped me think about things in new ways and reminded me what is important. My baby Jesse, thank you for being such a fun and happy little soul while I finished this work. Finally, this thesis is dedicated to my best friend and sister, Emily, for helping me to remember `one day at a time'. 2 Abstract This thesis uses functional transcranial Doppler sonography (fTCD) to inves- tigate hemispheric asymmetries in brain activity during language processing. FTCD is a simple method that provides a measure of relative lateralisation. Given its portability and tolerance for movement, it allows physiological ac- tivity and behaviour to be measured simultaneously in understudied paedi- atric populations. The first half of the thesis describes three methodologically motivated studies with adults. The results indicated that the strength of lateralisation is affected by experimental manipulations of task and stimuli. A particularly influential factor was the intensity of phonological lexical search required. There was also an effect of stimulus pace, suggesting that difficulty or effort may also play a role in driving the strength of lateralisation. The second half of the thesis provides the main theoretical contributions to the literature in three developmental studies. The first found no evidence 1 of increases in the strength of lateralisation between the ages of 32 years 1 and 42 years. The second study found typical left-lateralisation during lan- guage production in a heterogeneous group of children born deaf. This study provides preliminary evidence that auditory input is not a contributory fac- tor to the development of language lateralisation. The final study used a paced picture naming task with children. Concordance was measured be- tween fTCD during this novel task and an established narrative task. The data also suggested that LIs measured by fTCD are most likely to relate to offline measures when the tasks share cognitive or linguistic demands. In summary, this thesis contributes to a growing body of research demon- strating that fTCD is a useful tool to investigate hemispheric lateralisation. It is of particular use with those populations for whom other neuroimag- ing modalities are not suitable. It is often these groups of participants who can offer unique insights into language processing and the underlying neural systems. Contents 1 Introduction 9 2 Theoretical background 12 2.1 Language lateralisation in adults . 12 2.1.1 Classical studies of language lateralisation . 12 2.1.2 Neuroimaging studies of language lateralisation . 15 2.1.3 Variability in language lateralisation . 22 2.2 Language lateralisation in children . 27 2.2.1 Neuroimaging studies of lateralisation in children . 27 2.2.2 The developmental trajectory of lateralisation . 30 2.3 Factors affecting the development of lateralisation . 33 2.3.1 Atypical hemispheric dominance in development . 33 2.3.2 The role of sensory input . 34 2.3.3 Deafness as a model system . 36 2.4 Chapter summary and research questions . 39 3 Methodological background 40 3.1 Transcranial Doppler sonography (TCD) . 40 3.1.1 Basic principles . 40 3.1.2 Visualisation of the TCD signal . 41 3.2 Functional TCD . 43 3.2.1 Physiological basis of the fTCD signal . 43 3.2.2 Experimental protocol . 44 3.2.3 Data analysis protocol . 45 3.3 Methodological issues to consider . 47 3.3.1 Reliability of fTCD for assessing language lateralisation 47 3.3.2 Limitations of fTCD . 48 4 Outline of the thesis 50 4.1 Research questions . 50 4.2 General procedure for Chapters 5 - 7 . 51 2 5 The effects of overt articulation and fluency type on lateral- isation 52 5.1 Introduction . 52 5.2 Method . 55 5.3 Results . 57 5.4 Discussion . 62 6 The effect of task demands on lateralisation 65 6.1 Introduction . 65 6.2 Experiment 1 . 68 6.2.1 Method . 68 6.2.2 Results . 72 6.2.3 Summary of Experiment 1 . 73 6.3 Experiment 2 . 74 6.3.1 Method . 74 6.3.2 Results . 76 6.3.3 Summary of Experiment 2 . 78 6.4 Discussion . 80 7 The effect of phonological demands on lateralisation 86 7.1 Introduction . 86 7.2 Method . 88 7.3 Results . 90 7.4 Discussion . 92 8 Summary of Chapters 5 - 7 95 9 The development of lateralisation in hearing children 97 9.1 Introduction . 97 9.2 Method . 100 9.3 Results . 103 9.4 Discussion . 111 10 Language lateralisation in children born deaf 116 10.1 Introduction . 116 10.2 Method . 119 10.3 Results . 123 10.4 Discussion . 128 11 Lateralisation of picture naming in hearing children 133 11.1 Introduction . 133 11.2 Methods . 136 3 11.3 Results . 138 11.4 Discussion . 142 12 General Discussion 147 12.1 Developmental factors which relate to left hemisphere lateral- isation for language . 147 12.1.1 Age . 148 12.1.2 Language exposure . 148 12.1.3 Language proficiency . 149 12.2 Analysis in future studies using fTCD . 153 12.2.1 Processing steps in the fTCD analysis pipeline . 153 12.2.2 Estimating fTCD reliability . 154 12.2.3 Calculation of LI . 156 12.3 Interpretation of fTCD data in future studies . 157 12.3.1 Strength or direction of lateralisation . 157 12.3.2 Importance of task related effects . 159 12.4 Conclusion . 160 13 Appendix 161 .1 Words pairs for Chapter 6 . 161 4 List of Figures 2.1 Physiological changes and the major neuroimaging methods. Adapted from Deppe et al. (2004) . 17 3.1 Screenshot of QL monitoring software. 42 3.2 Screenshot of QL monitoring software with m-mode window. 42 3.3 Vascular territories of the major cerebral arteries. 44 5.1 Scheme for trial timings of phonological and semantic fluency tasks. 57 5.2 LI scatterplots for each condition. The LIs for atypical indi- viduals in any of the four conditions are shape coded. Each shape consistently represents a participant across all conditions. 60 5.3 The relationship between number of words and laterality in- dices in covert (top panel) and overt (bottom panel) conditions 61 6.1 Stimuli for rhyme judgement (A) and line judgement (B) . 70 6.2 Scheme for trial timings in Experiment 1. 71 6.3 Scheme for trial timings in Experiment 2. 75 6.4 Relationship between LIs at different stimulus presentation speeds. Bars indicate standard errors. Positive LIs indicate left-lateralisation, negative LIs denote right-lateralisation. 77 6.5 Lateralisation Indices in rhyme and line tasks. Bars indicate standard errors. Positive LIs indicate left-lateralisation, neg- ative LIs denote right-lateralisation. 78 6.6 Average blood flow change during each condition . 79 6.7 The spread of LIs for individuals performing each of the tasks 80 7.1 Timing of trials for the Reading and Rhyming tasks . 89 7.2 Plot of individual LIs in each condition, Naming (referred to in text as Reading), and Rhyming. 91 7.3 Group averaged CBFV changes for the Reading task. 92 7.4 Group averaged CBFV changes for the Rhyming task . 92 5 7.5 Relationship between strength of LI and amount of trials con- taining an utterance. 93 9.1 Scheme of animation description task . 103 9.2 Group averaged changes in CBFV during Animation Descrip- tion at each time point. Shaded areas show the standard error at each sample point. 105 9.3 Distribution of LIs at each time point. 107 9.4 LIs with standard errors for each time point . 108 9.5 Strength of lateralisation and number of letters known at T2. 110 9.6 Reproducibility of LIs from Time 1 (x axes) to Time 2 (y axes) for each analysis type. 110 9.7 For illustrative purposes: calculating the LI from maximum differences versus whole period. 112 10.1 Group averaged changes in CBFV during Animation Descrip- tion. 125 10.2 CBFV changes for CI and non-CI subgroups . 127 10.3 Laterality Indices for all children. 131 11.1 Timings for each trial of the Animation Description and Picutre Naming tasks. 138 11.2 Group averaged changes in CBFV during Picture Naming and Animation Description tasks. Shaded areas indicate standard errors at each sample point. 141 11.3 Consistency between period and peak calculations for Anima- tion description. 142 11.4 Consistency between period and peak LI calculations for Pic- ture naming. 143 6 List of Tables 5.1 Mean number of words produced per trial in each condition . 58 5.2 Descriptives of Laterality Indices and number of participants categorized as left, right, or low lateralised . 59 6.1 Examples of rhyme judgement stimuli .