VISUAL REHABILITATION AND REORGANIZATION: CASE STUDIES OF CORTICAL PLASTICITY IN PATIENTS WITH AGE-RELATED MACULAR DEGENERATION A Dissertation Presented to The Academic Faculty by Keith Leonard Main In Partial Fulfillment of the Requirements for the Degree Doctorate of Philosophy in the School of Psychology Georgia Institute of Technology December 2010 Copyright © 2010 by Keith L. Main VISUAL REHABILITATION AND REORGANIZATION: CASE STUDIES OF CORTICAL PLASTICITY IN PATIENTS WITH AGE-RELATED MACULAR DEGENERATION Approved by: Dr. Eric H. Schumacher, Advisor Dr. Audrey Duarte School of Psychology School of Psychology Georgia Institute of Technology Georgia Institute of Technology Dr. Paul Corballis Dr. Susan A. Primo School of Psychology School of Medicine Georgia Institute of Technology Emory University Dr. Paul Verhaehgen School of Psychology Georgia Institute of Technology Date Approved: Sept 1st, 2010 To my mother and father, who’ve made all this possible. ACKNOWLEDGEMENTS I wish to thank Eric Schumacher for his support and guidance as my advisor. I owe Susan Primo a great debt for her kindness, expertise, and dedication to this project. Thanks to Donna Inkster and Jeff Horton. Your efforts were crucial to patient recruitment and data collection. I would also like to thank rest of my committee: Paul Corballis, Audrey Duarte, and Paul Verhaehgen. Your assistance has been invaluable and willingness to write recommendation letters seemingly inexhaustible! My lab mates deserve a special acknowledgement for tolerating my antics for five years. Hillary, Erin and Temi, thank you and best of luck to you in the wild world. Remember, you have a friend out there. Greg Corso and Jan Westbrook, I would have floundered in this program long ago if you hadn’t steered me through red tape. Thank you. Next to last, I cannot forget the biggest contributors of all. The patients that volunteered their time and entrusted their welfare to me deserve a special thanks. It was a pleasure to get to know you and be a part of your lives, if only for a short while. You gave me your time, patience, and cooperation. I hope I have done your investment justice. I hope we’re one step closer to understanding human potential in relation to MD. Thank you for helping me to become a scientist. Finally, my deepest gratitude goes to my family. Mom, Dad, Brian, and Elliot, I’m done! But it’s just the beginning. iv TABLE OF CONTENTS ACKNOWLEDGEMENTS.............................................................................................. IV TABLE OF CONTENTS................................................................................................... V LIST OF FIGURES .......................................................................................................... IX SUMMARY.....................................................................................................................XII CHAPTER 1: INTRODUCTION....................................................................................... 1 CHAPTER 2: MACULAR DEGENERATION ................................................................. 7 2.1 MD Classification ......................................................................................................... 9 2.2 Pathophysiology.......................................................................................................... 10 2.3 Functional Deficits...................................................................................................... 11 2.3.1 The Central Scotoma ........................................................................................... 11 2.3.2 Scotoma Measurement......................................................................................... 14 2.3.3 Behavioral Consequences.................................................................................... 16 2.4 Patient Adaptation....................................................................................................... 18 2.4.1 The Preferred Retinal Locus................................................................................ 18 2.4.2 Multiple PRLs and Binocular Vision................................................................... 19 2.4.3 Theories of PRL Development ............................................................................ 21 2.5 Low Vision Rehabilitation.......................................................................................... 23 CHAPTER 3: CORTICAL REORGANIZATION........................................................... 26 3.1 Mechanisms of Adult Plasticity.................................................................................. 26 3.1.1 Synaptic Plasticity................................................................................................ 27 3.1.2 Map Plasticity ...................................................................................................... 28 3.2 Reorganization from Deafferentation ......................................................................... 29 3.2.1 The Somatosensory and Auditory Cortices ......................................................... 30 v 3.2.2 Amputation and Phantom Limbs ......................................................................... 32 3.3 Reorganization from Training..................................................................................... 33 3.3.1 Sensory Discrimination in Animals..................................................................... 34 3.3.2 The Musician’s Brain........................................................................................... 35 3.4 Visual Reorganization................................................................................................. 37 3.4.1 The Visual Cortex................................................................................................ 37 3.4.2 Animal Models .................................................................................................... 39 3.4.3 The Process of Reorganization ............................................................................ 41 3.4.4 Blindness and Retinal Lesions............................................................................. 43 CHAPTER 4: MD AND REORGANIZATION............................................................... 46 CHAPTER 5: CURRENT STUDY .................................................................................. 55 5.1 Design ......................................................................................................................... 55 5.2 Behavioral Hypotheses ............................................................................................... 56 5.3 Neuroimaging Hypotheses.......................................................................................... 57 CHAPTER 6: METHOD .................................................................................................. 59 6.1 Patients........................................................................................................................ 59 6.2 Apparatus .................................................................................................................... 61 6.2.1 Behavioral Testing............................................................................................... 61 6.2.2 MP-1 Evaluation/Training ................................................................................... 61 6.2.3 Functional Neuroimaging .................................................................................... 62 6.3 General Procedure....................................................................................................... 63 6.3.1 Initial Evaluation.................................................................................................. 64 6.3.2 Behavioral Assessment ........................................................................................ 68 6.3.3 Neuroimaging Assessment .................................................................................. 81 6.3.4 Visual Rehabilitation ........................................................................................... 87 CHAPTER 7: DATA ANALYSIS ................................................................................... 92 vi CHAPTER 8: RESULTS.................................................................................................. 95 8.1 Evaluation Results ...................................................................................................... 95 8.1.1 Microperimetry .................................................................................................... 95 8.1.2 Fixation Analysis ................................................................................................. 99 8.1.3 PRL/nonPRL Determination.............................................................................. 101 8.2 Rehabilitation Results ............................................................................................... 103 8.2.1 Occupational Therapy........................................................................................ 103 8.2.2 Biofeedback ....................................................................................................... 104 8.3 Assessment Results................................................................................................... 107 8.3.1 Behavioral Tests ................................................................................................ 107 8.3.2 Functional Neuroimaging 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