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Pupillary Light Reflex in Children with Autism Spectrum Disorders

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Pupillary Light Reflex in Children with Autism Spectrum Disorders PUPILLARY LIGHT REFLEX IN CHILDREN WITH AUTISM SPECTRUM DISORDERS _______________________________________________________ A Dissertation presented to the Faculty of the Graduate School at the University of Missouri‐Columbia _______________________________________________________ In Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy _______________________________________________________ by CHATHURI DALUWATTE Dr. Gang Yao, Dissertation Supervisor MAY 2013 The undersigned, appointed by the dean of the Graduate School, have examined the dissertation entitled PUPILLARY LIGHT REFLEX IN CHILDREN WITH AUTISM SPECTRUM DISORDERS presented by Chathuri Daluwatte, a candidate for the degree of Doctor of Philosophy, and hereby certify that, in their opinion, it is worthy of acceptance. Dr. Gang Yao, Department of Biological Engineering Dr. Judith H. Miles, Thompson Center for Autism & Neurodevelopmental Disorders Dr. Shawn Christ, Department of Psychological Sciences, Thompson Center for Autism & Neurodevelopmental Disorders Dr. Shinghua Ding, Department of Biological Engineering Dr. John Viator, Department of Biological Engineering To Ammi… ACKNOWLEDGEMENTS I wish to express my heartiest gratitude to Dr. Gang Yao, who has served as my advisor during the past four and half years. The inspiration he has been setting was a major driving force throughout my research and I will forever be grateful to Dr. Yao for the challenging way he improved my logical thinking, scientific methodology and professionalism. My deep appreciation is expressed to Dr. Judith H. Miles, for her warmest encouragements, insights and all the guidance throughout the research. She has been a great inspiration for me. I am grateful to Dr. Shawn Christ and Dr. David Beversdorf for their valuable contributions which tremendously improved the quality of this research. I would also like to express my gratitude for Jill Akers and Nicole Takahashi for their amazing job in recruiting and coordinating such a large number of research participants. Had it not been for them this research would not have been possible. I also want to express my warmest gratitude for Andrew Lofgreen and Nathan Berliner for their support in recruiting the large group of control participants and their help in image processing and data entry. I am also indebted to my dissertation committee members Dr. John Viator and Dr. Shinghua Ding for their valuable advice. I am deeply grateful to Dr. Xiaofei Fan who supported me during the early stage of the study to get a smooth start with the project. I am thankful for my colleagues in our research group, Dr. Chuanmao Fan, Randima Dinalankara and Ben Davis for the fruitful discussions and support and above all for their friendship. I would like to ii especially be thankful to Dr. Ali Shauib who generously helped me a lot during the testing stages of the research. I am deeply thankful to my best friend Awanthi Hewage, without whose support and unshaken friendship I would not have made it through graduate school. Ultimately, I am grateful for the love and support of my mother, who has been the source of strength in my life. I sincerely appreciate all her support and patience which is the sole reason for my success. iii TABLE OF CONTENTS ACKNOWLEDGEMENTS ................................................................................................ II LIST OF FIGURES .......................................................................................................... VI LIST OF TABLES .......................................................................................................... VIII LIST OF ACRONYMS ...................................................................................................... X ABSTRACT .................................................................................................................. XII Chapter Page 1 INTRODUCTION ..................................................................................................... 1 1.1 Pupillary Light Reflex ......................................................................................................................... 1 1.1.1 Introduction ............................................................................................................................. 1 1.1.2 Neurological Pathway of PLR ................................................................................................... 1 1.1.3 PLR Parameters ....................................................................................................................... 8 1.1.4 Applications of PLR ................................................................................................................ 10 1.2 Heart Rate Variability ...................................................................................................................... 12 1.2.1 Neurological Pathway ........................................................................................................... 13 1.2.2 HRV Parameters .................................................................................................................... 15 1.2.3 Physiological Correlations and Reproducibility ...................................................................... 23 1.2.4 Applications of HRV ............................................................................................................... 24 1.3 Summary of this Dissertation Study ................................................................................................ 25 2 INSTRUMENTATION ............................................................................................ 27 2.1 Binocular Pupilogram Recording System ........................................................................................ 27 2.2 Calibration ....................................................................................................................................... 28 2.3 Image Processing ............................................................................................................................ 30 2.4 Extracting PLR Parameters .............................................................................................................. 35 2.5 Conclusions ..................................................................................................................................... 39 3 SIMULTANEOUSLY MEASURED PUPILLARY LIGHT REFLEX AND HEART RATE VARIABILITY IN HEALTHY CHILDREN .................................................................... 41 3.1 Introduction .................................................................................................................................... 41 3.2 Methods .......................................................................................................................................... 43 3.2.1 Participants ............................................................................................................................ 43 3.2.2 Instrument ............................................................................................................................. 44 3.2.3 Test Procedure ....................................................................................................................... 44 3.2.4 Data Analysis ......................................................................................................................... 45 3.3 Results ............................................................................................................................................. 48 3.3.1 Pupillary Light Reflex ............................................................................................................. 48 3.3.2 Heart Rate Variability ............................................................................................................ 49 3.3.3 Interrelationship between PLR and HRV ................................................................................ 49 3.4 Discussion........................................................................................................................................ 53 3.5 Conclusion ....................................................................................................................................... 56 iv 4 AGE‐DEPENDENT PUPILLARY LIGHT REFLEX PARAMETERS IN CHILDREN ............. 57 4.1 Introduction .................................................................................................................................... 57 4.2 Methods .......................................................................................................................................... 60 4.2.1 Test Procedure ....................................................................................................................... 60 4.2.2 Data analysis ......................................................................................................................... 61 4.3 Results ............................................................................................................................................. 61 4.4 Discussion........................................................................................................................................ 64 4.5 Conclusion ....................................................................................................................................... 67 5 ATYPICAL PUPILLARY LIGHT REFLEX AND HEART RATE VARIABILITY IN CHILDREN WITH AUTISM SPECTRUM
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