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Understanding Eye Movements and Attentional Mechanisms Is Key to Improving Amblyopia Treatment

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Understanding Eye Movements and Attentional Mechanisms Is Key to Improving Amblyopia Treatment Bridging the Gap: Understanding Eye Movements and Attentional Mechanisms is Key to Improving Amblyopia Treatment By Christina Grace Gambacorta A dissertation submitted in partial satisfaction of the requirements for the degree of Doctor of Philosophy in Vision Science in the Graduate Division of the University of California, Berkeley Committee in charge: Professor Dennis Levi, Chair Senior Scientist Suzanne McKee Professor Stanley Klein Professor Richard Ivry Summer 2017 Abstract Bridging the Gap: Understanding Eye Movements and Attentional Mechanisms is Key to Improving Amblyopia Treatment by Christina Grace Gambacorta Doctor of Philosophy in Vision Science University of California, Berkeley Professor Dennis Levi, Chair Amblyopia is a developmental visual disorder resulting in sensory, motor and attentional deficits, including delays in both saccadic and manual reaction time. It is unclear whether this delay is due to differences in sensory processing of the stimulus, or the processes required to dis-engage/shift/re-engage attention when moving the eye from fixation to a saccadic target. In the first experiment we compare asymptotic saccadic and manual reaction times between the two eyes, using equivalent stimulus strength to account for differences in sensory processing. In a follow-up study, we modulate RT by removing the fixation dot, which is thought to release spatial attention at the fovea, and reduces reaction time in normal observers. Finally, we discuss the implications for these findings on future amblyopic treatment, specifically dichoptic video game playing. Playing videogames may help engage the attentional network, leading to greater improvements than traditional treatment of patching the non- amblyopic eye. Further, when treatment involves both eyes, fixation stability may be improved during the therapeutic intervention, yielding a better outcome than just playing a video game with a patch over the non-amblyopic eye. 1 Dedication This thesis is dedicated to my grandfather, Rocco Gambacorta, who’s lifelong passion for learning had a large impact on me at an early age. I’d also like to thank Shmuel Link for his patience and healthy cooking, and my rabbit, waffles, who encouraged me to share treats during writing breaks. I’d like to acknowledge my advisor, Dennis Levi and committee members, in particular Suzanne McKee, who provided invaluable support during my time at Smith Kettlewell Eye Research institute. Finally, I’d also like to thank my fellow lab mates, colleagues, and research assistants at Berkeley and SKERI. i Contents 1 Introduction .......................................................................................................... 1 1.1 What is amblyopia? ...................................................................................... 1 1.2 Clinical significance ........................................................................................ 2 1.3 Vision as an active process ........................................................................... 2 1.4 Reaction times are longer when viewing with the amblyopic eye ................... 3 1.5 Pieron’s law .................................................................................................. 4 1.6 Aim 1 Overview ............................................................................................ 4 1.7 Fixation and foveal attention may be disrupted ............................................. 5 1.8 Introducing the gap ...................................................................................... 6 1.9 Aim 2 Overview ............................................................................................ 9 1.10 Improving amblyopia treatment ..................................................................... 9 1.11 Aim 3 Overview .......................................................................................... 11 1.12 Summary .................................................................................................... 12 2 Reaction Time in Amblyopia as a Function of Equivalent Contrast ................. 13 2.1 Introduction ................................................................................................. 13 2.1.1 Overview of the saccadic neural circuitry ........................................ 13 2.1.2 Saccadic timing and execution ....................................................... 15 2.1.3 Saccadic timing in depth ................................................................ 16 2.1.4 Modeling reaction time to visual stimuli ........................................... 19 2.1.5 Saccadic latency is increased in patients with amblyopia ................ 21 2.1.6 Hypotheses for Aim 1 ..................................................................... 23 2.2 Methods ..................................................................................................... 24 2.2.1 Procedure ..................................................................................... 24 2.2.2 Analysis ......................................................................................... 26 2.2.3 Study participants .......................................................................... 26 2.3 Results ....................................................................................................... 29 2.3.1 Saccadic reaction times ................................................................. 29 2.3.2 Manual reaction times ..................................................................... 31 ii 2.3.3 Variability in response times ........................................................... 34 2.3.4 Relationship between reaction time and sensitivity ......................... 36 2.3.5 Relationship between saccadic latency and manual reaction time .. 37 2.3.6 Parallel vs. intersecting Burr functions ............................................. 38 2.4 Discussion ................................................................................................... 39 3 Modulating Fixation Offset: The Gap Effect in Amblyopia ............................... 43 3.1 Introduction ................................................................................................. 43 3.1.1 Gap effect ...................................................................................... 43 3.1.2 Neurophysiology of the gap effect .................................................. 46 3.1.3 Temporal encoding hypothesis: large implications for perception .... 49 3.1.4 Measuring fixation stability in normal and patient populations .......... 50 3.1.5 Hypotheses for Aim 2 ..................................................................... 57 3.2 Methods ..................................................................................................... 58 3.2.1 Procedure ..................................................................................... 58 3.2.2 Analysis ......................................................................................... 58 3.2.3 Study participants .......................................................................... 59 3.3 Results ....................................................................................................... 60 3.3.1 Saccadic reaction times with a gap ............................................... 61 3.3.2 The gap does not eliminate the irreducible delay ............................. 62 3.3.3 Gap effect and visibility indices ...................................................... 63 3.4 Discussion ................................................................................................... 64 4 Dichoptic Video Games as a Treatment for Children with Amblyopia ............. 67 4.1 Introduction ................................................................................................. 67 4.1.1 Amblyopia treatment ...................................................................... 70 4.1.2 Study aims ..................................................................................... 89 4.2 Methods ..................................................................................................... 90 4.2.1 Study participants and ethics statement ........................................ 90 4.2.2 Study design overview .................................................................... 92 4.2.3 Study interventions ........................................................................ 93 iii 4.2.4 Dichoptic game mode ................................................................... 95 4.2.5 Monocular game mode .................................................................. 96 4.2.6 Visual function assessments .......................................................... 96 4.2.7 Data analysis ................................................................................. 97 4.3 Results ....................................................................................................... 98 4.3.1 Changes in clinical visual acuity ..................................................... 98 4.3.2 Changes in stereoacuity ............................................................... 100 4.3.3 Changes in contrast sensitivity ..................................................... 100 4.3.4 Changes in reading ability ............................................................ 101 4.3.5 Follow-up assessments ............................................................... 101 4.3.6 Dynamics of visual function change ............................................. 102 4.3.7 Changes in dependent variables
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