The Texas Medical Center Library DigitalCommons@TMC The University of Texas MD Anderson Cancer Center UTHealth Graduate School of The University of Texas MD Anderson Cancer Biomedical Sciences Dissertations and Theses Center UTHealth Graduate School of (Open Access) Biomedical Sciences 5-2010 Eye Movement Measures of Cognitive Control in Children with Tourette Syndrome Cameron B. Jeter Follow this and additional works at: https://digitalcommons.library.tmc.edu/utgsbs_dissertations Part of the Cognitive Neuroscience Commons, Nervous System Diseases Commons, Other Psychiatry and Psychology Commons, and the Systems Neuroscience Commons Recommended Citation Jeter, Cameron B., "Eye Movement Measures of Cognitive Control in Children with Tourette Syndrome" (2010). The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access). 26. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/26 This Dissertation (PhD) is brought to you for free and open access by the The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at DigitalCommons@TMC. It has been accepted for inclusion in The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access) by an authorized administrator of DigitalCommons@TMC. For more information, please contact [email protected]. EYE MOVEMENT MEASURES OF COGNITIVE CONTROL IN CHILDREN WITH TOURETTE SYNDROME by Cameron Beth Jeter, B.A. APPROVED: _____________________________________ Anne B. Sereno, Ph.D., Supervisory Professor _____________________________________ Ian J. Butler, M.D. _____________________________________ Pramod K. Dash, Ph.D. _____________________________________ Jeffrey S. Morris, Ph.D. _____________________________________ M. Neal Waxham, Ph.D. APPROVED: _____________________________________ Dean, The University of Texas Graduate School of Biomedical Sciences at Houston i EYE MOVEMENT MEASURES OF COGNITIVE CONTROL IN CHILDREN WITH TOURETTE SYNDROME A DISSERTATION Presented to the Faculty of The University of Texas Health Science Center at Houston and The University of Texas M. D. Anderson Cancer Center Graduate School of Biomedical Sciences in Partial Fulfillment of the Requirements for the Degree of DOCTOR OF PHILOSOPHY by Cameron Beth Jeter, B.A. Houston, Texas May, 2010 i You are the Sovereign Holy One, LORD Worshipped, Magnified Honored, Adored. Intercessor, Advocate Counselor, Friend Faithful Emmanuel On whom I depend. “Whatever you do, work at it with all your heart, as working for the Lord, not for men.” Colossians 3:23 “Commit your works to the LORD, and your thoughts will be established.” Proverbs 16:3 iii Acknowledgements I have many, many people to thank for my success. Thank you, Dr. Sereno, my advisor, for teaching me not to strive for perfection, but to strive to persevere through the inevitable ups and downs of science. Thank you, Dr. Saumil Patel, for your unceasing and cheerful scientific help, advice, and friendship. Fernando Latunio, thank you for being my family away from home, serving as a prayer partner, intercessor, and confidant. Drs. Shelly Fontenot and Ashley Hood, thanks for going before me, always gladly showing me the ropes, and cheering me on to the finish. I couldn’t have remained sane without you girls. Thank you to my Supervisory Committee members – Dr. Dash, for investing in my scientific past (committees) and future (postdoc); Dr. Morris, for hours of explaining statistics in an uncannily clear way; Dr. Waxham, for being a voice of reason and reliable good advice. Thank you, Dr. Butler, for so agreeably collaborating with me on this project. You not only let me tag along in the clinic, but also welcomed me wholeheartedly. Thank you, Nia Ramirez and Edith Mendoza, for readily and capably adding my study to your nursing duties. Also, thanks to the fellows, residents, and medical students who took an interest in and aided my work. Of course, I extend great thanks to the Tourette Syndrome patients and their families who gave of themselves and their time to share their experiences with me and to participate in my study. Equal thanks goes to the children and families who served as control participants. I am indebted to my church family for your eager participation and help. Thank you, Barbara Chrisman, for giving first-hand advice about working with children generally and those with Tourette Syndrome specifically, and Mike Bonem for publicizing the call for help. Thank you, Michelle Reith, for your industrious typing on my behalf, working faster than I could have myself. Thank you, Dr. Landrum, for your genuine interest and support of my study, which extends far beyond an obligatory role in pastoral care. Thank you to my invaluable funding sources. I am grateful for five years of NIH training grant support, both the “Training in Neuroscience” institutional grant and the Center for Clinical and Translational Sciences T32 training grant. Thank you is not enough to the ladies of the AC chapter of the Philanthropic Educational Organization (PEO). Beyond the generous financial support you provided me, you consistently applauded me as one of your own. Finally, thank you to my family. I do not take your support and love for granted. Thanks, Dad and Mom, for hours of advice over the phone. Ashley, thanks for the chats and cards. Sam, thanks for talking neuroscience with me. David, my love, thank you for years of patient, unselfish love and support. I couldn’t have done it without you. iv EYE MOVEMENT MEASURES OF COGNITIVE CONTROL IN CHILDREN WITH TOURETTE SYNDROME Publication No.___________ Cameron Beth Jeter, Ph.D. Supervisory Professor: Anne B. Sereno, Ph.D. Tourette Syndrome begins in childhood and is characterized by uncontrollable repetitive actions like neck craning or hopping and noises such as sniffing or chirping. Worst in early adolescence, these tics wax and wane in severity and occur in bouts unpredictably, often drawing unwanted attention from bystanders. Making matters worse, over half of children with Tourette Syndrome also suffer from comorbid, or concurrent, disorders such as attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). These disorders introduce anxious thoughts, impulsivity, inattention, and mood variability that further disrupt children with Tourette Syndrome from focusing and performing well at school and home. Thus, deficits in the cognitive control functions of response inhibition, response generation, and working memory have long been ascribed to Tourette Syndrome. Yet, without considering the effect of medication, age, and comorbidity, this is a premature attribution. This study used an infrared eye tracking camera and various computer tasks requiring eye movement responses to evaluate response inhibition, response generation, and working memory in Tourette Syndrome. This study, the first to control for medication, age, and comorbidity, enrolled 39 unmedicated children with Tourette Syndrome and 29 typically developing peers aged 10-16 years who completed reflexive and voluntary eye movement tasks and diagnostic rating scales to assess symptom severities of Tourette Syndrome, ADHD, and OCD. Children with Tourette Syndrome and comorbid ADHD and/or OCD, but not children with Tourette Syndrome only, took longer to respond and made more errors and distracted eye movements compared to typically- developing children, displaying cognitive control deficits. However, increasing symptom severities of Tourette Syndrome, ADHD, and OCD correlated with one another. Thus, cognitive control deficits were not specific to Tourette Syndrome patients with comorbid conditions, but rather increase with increasing tic severity, suggesting that a majority of Tourette Syndrome patients, regardless of a clinical diagnosis of ADHD and/or OCD, have symptoms of cognitive control deficits at some level. Therefore, clinicians should evaluate and counsel all families of children with Tourette Syndrome, with or without currently diagnosed ADHD and/or OCD, about the functional ramifications of comorbid symptoms and that they may wax and wane with tic severity. v Table of Contents 1. CHAPTER 1 1 INTRODUCTION 1 Diagnosis and Prevalence 2 Natural History 5 Comorbidities 6 Etiology and Genetics 9 Pathophysiology 10 2. CHAPTER 2 18 ORIENTING IN TS 18 Eye Movements 19 Value of Saccade Research 21 Model of Orienting in TS 23 Previous Eye Movement Studies in TS 24 Current Study 30 Research Plan Part 1: Classic Oculomotor Tasks 31 Research Plan Part 2: Novel Spatial N-back Tasks 32 Research Plan Part 3: Factor Analysis 35 3. CHAPTER 3 36 METHODS 36 Study Participants 37 Diagnostic Measures 38 General Procedure 39 Eye Movement Tasks 40 Behavioral Testing Procedure 50 Data Analysis 53 4. CHAPTER 4 54 RESULTS 54 Control and Tourette Syndrome Participants 55 Control and Tourette Syndrome Participants Divided by Comorbid Status 60 Part 1: Classic Oculomotor Tasks – Prosaccade and Antisaccade 63 Part 2: Novel Spatial N-back Tasks – 0-back and 1-back 68 Part 3: Factor Analysis – Eye Movement Variables and Rating Scale Totals/Subscales 75 vi 5. CHAPTER 5 83 DISCUSSION 83 Collective Results 84 ADHD and OCD in TS: Additional or Integral? 86 TS-only Patients: Tics, but No Cognitive Control Impairments? 88 TS-comorbid Patients: What Pathology Causes Cognitive Control Deficits? 90 Updated Model of Orienting in TS 92 Alternative Model 95 Future Directions 96