Studies of Somatosensory and Pain Neural Circuits with High Field
Total Page：16
File Type：pdf, Size：1020Kb
STUDIES OF SOMATOSENSORY AND PAIN NEURAL CIRCUITS WITH HIGH FIELD FUNCTIONAL MRI By Elizabeth Ann Stringer Dissertation Submitted to the Faculty of the Graduate School of Vanderbilt University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY in Neuroscience December, 2010 Nashville, Tennessee Approved: Professor Stephen Bruehl Professor Li Min Chen Professor John C. Gore Professor Jon Kaas Professor Ronald Wiley For my grandfather, John Charles Katz ii ACKNOWLEDGMENTS This research would not have been possible without the financial support of the National Institutes of Health through grants awarded to my advisor, Dr. John C. Gore. Most significantly the EB000461 grant has supported my research on the 7-T MR scanner for the last three years, and the T32 EB003817 predoctoral training grant supported two years of my research. I must acknowledge and thank my advisor Dr. Gore for taking a chance on me when I was a first year graduate student. He provided the finances that allowed me to acquire data whenever I needed to, procure new equipment, travel to conferences, and the list goes on. My research could not have been accomplished without the Vanderbilt University Institute of Imaging Science’s (VUIIS) 7-T scanner and the group of interdisciplinary scientists that keep it operational for human research. None of this would have been possible without Dr. Gore’s vision. I thank my committee members for encouraging me in my research. Their genuine interest in my projects has served as wonderful motivation. Dr. Li Min Chen has been a co-advisor to me and has taught me a great deal about sensory systems and manuscript writing, and her guidance has been critical to my development as a scientist. Dr. Ronald Wiley, my committee chair, has let me participate in his lab meetings and taught me to appreciate the complexity of the pain system, of which previously I had had only a superficial understanding. My other committee members, Dr. Stephen Bruehl and Dr. Jon Kaas, have each met with me on multiple occasions to assess my data, answer questions, and offer positive outlooks on the future. Although not on my committee, Dr. Robert Friedman has given me his unwavering support and has taught me so much about science from electronics to physiology. Much of the data was acquired with Dr. Friedman’s help, and he developed iii the electronics we used in our studies. He has been a true mentor to me and I thank him for all his time and efforts. I thank the many members of the VUIIS that have helped me along the way. Specifically Dr.’s Christopher Gatenby, Baxter Rogers, Allen Newton, and Robert Barry have all been integral in data acquisition, analysis, and interpretation. The VUIIS MR technologists have all helped with screening subjects and getting subjects into the scanner for data acquisition. Nancy Hagans is our administrator extraordinaire and has assisted me in many things over the last six years. My family and friends have been so supportive of me during my graduate school experience, and I never would have made it through without them. My cousin Christina Rodriguez was the best roommate I could ask for and did her best to get me to balance the work with some fun. My cousin Christina Stringer has been my dissertation writing partner and without her support I’m not sure I would have had the motivation to “put pen to paper.” My sister and best friend, Marie Yeagle, my brother-in-law, Jeremy Yeagle, my grandparents, Nancy and John Katz, and my parents, Pete and Bella Stringer, have been the most encouraging cheerleading section. They have made this document possible by persuading me not to give up time and time again. And last but not least, I thank Trey House for his unconditional love. iv TABLE OF CONTENTS Page DEDICATION ..................................................................................................................ii ACKNOWLEDGMENTS.................................................................................................iii LIST OF FIGURES........................................................................................................vii Chapter I. INTRODUCTION .........................................................................................................1 Primary Somatosensory Cortex........................................................................1 Somatic Sensation.............................................................................................3 Pain.....................................................................................................................6 Neuroimaging...................................................................................................10 Specific Aims ...................................................................................................22 References .......................................................................................................22 II. DIFFERENTITATION OF SOMATOSENSORY CORTICES BY HIGH-RESOLUTION FMRI AT 7 T.............................................................................................................27 Abstract ............................................................................................................27 Introduction......................................................................................................28 Methods............................................................................................................31 Results..............................................................................................................36 Discussion........................................................................................................44 Conclusion .......................................................................................................49 References .......................................................................................................50 III. DISTICTIVE CORTICAL RESPONSES TO TACTION IN SUBREGIONS OF PRIMARY SOMATOSENSORY CORTEX. ..............................................................55 Abstract ............................................................................................................55 Introduction......................................................................................................56 Methods............................................................................................................58 Results..............................................................................................................62 Discussion........................................................................................................82 Conclusion .......................................................................................................88 References .......................................................................................................89 IV. IDENTIFICATION AND MODULATION OF RESTING STATE FUNCTIONAL CONNECTIVITY IN THE LATERAL PAIN NETWORK ...........................................93 Abstract ............................................................................................................93 Introduction......................................................................................................94 Materials and Methods ....................................................................................96 v Results............................................................................................................117 Discussion......................................................................................................119 References .....................................................................................................120 V. CONCLUSION AND FUTURE DIRECTIONS ........................................................123 Conclusions ...................................................................................................123 Future Directions ...........................................................................................127 Development of fMRI at 7 T ......................................................................128 Activation in Ipsilateral SI.........................................................................129 “Negative” BOLD Signal...........................................................................134 Areas Beyond SI .......................................................................................138 Dynamic Changes in Functional Connectivity........................................143 References .....................................................................................................144 vi LIST OF FIGURES Figure Page 1. Cytoarchitectural subdivisions within SI.................................................................. 3 2. Dorsal columns and medial lemniscus pathway...................................................... 5 3. Spinothalamic pathway.............................................................................................. 8 4. Supraspinal pain processing....................................................................................10 5. Imaging and air puff experimental setup .................................................................32 6. Digit response contrast maps ..................................................................................38 7. Surface composite maps of digit topography .........................................................40 8. Spatial reproducibility