University of South Carolina Scholar Commons Theses and Dissertations 2015 Correlations Between White Matter Integrity, Structural Connectivity, And Upper and Lower Extremity Motor Function in Individuals With Chronic Stroke Denise M. Peters University of South Carolina Follow this and additional works at: https://scholarcommons.sc.edu/etd Part of the Exercise Science Commons Recommended Citation Peters, D. M.(2015). Correlations Between White Matter Integrity, Structural Connectivity, And Upper and Lower Extremity Motor Function in Individuals With Chronic Stroke. (Doctoral dissertation). Retrieved from https://scholarcommons.sc.edu/etd/3680 This Open Access Dissertation is brought to you by Scholar Commons. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of Scholar Commons. For more information, please contact [email protected]. CORRELATIONS BETWEEN WHITE MATTER INTEGRITY, STRUCTURAL CONNECTIVITY, AND UPPER AND LOWER EXTREMITY MOTOR FUNCTION IN INDIVIDUALS WITH CHRONIC STROKE by Denise M. Peters Bachelor of Science University of Alabama-Birmingham, 2001 Doctor of Physical Therapy University of South Carolina, 2007 Submitted in Partial Fulfillment of the Requirements For the Degree of Doctor of Philosophy in Exercise Science The Norman J. Arnold School of Public Health University of South Carolina 2015 Accepted by: Stacy L. Fritz, Major Professor Jill C. Stewart, Committee Member Jessica D. Richardson, Committee Member Troy M. Herter, Committee Member Roger D. Newman-Norlund, Committee Member Lacy Ford, Senior Vice Provost and Dean of Graduate Studies © Copyright by Denise M. Peters, 2015 All Rights Reserved. ii DEDICATION For my family… To my partner, who supported me throughout this journey with amazing patience, even as the years kept adding up. You enabled me to pursue this degree while starting a family, something that was not without its challenges for the both of us, and I thank you greatly for this. Through unexpected twists and turns, you lent a guiding hand, a supportive voice, and were someone who I could always count on. To my daughters, who taught me more about time management and made me laugh during even the most stressful of times. You helped me learn more about balance in my life, and to not lose focus on finding joy in each day. To my mother, who has always supported and encouraged her children to seek out opportunities to further their education. Without you, this dissertation would have probably taken another year to complete…thank you for driving countless miles to help take care of your grandkids so that I could have uninterrupted time to focus on my studies/research. And to my father, whom I miss each and every day. You were always a role model to me, so much so that I tried to be a permanent graduate student just like you. You taught me the meaning of unconditional love and support, and to be kind to people of all walks of life. You always gave the best advice, which I drew upon many times during this journey. Thank you…for everything…I miss you. iii ACKNOWLEDGEMENTS I would like to thank Stacy Fritz…my mentor and my friend, who gave me the space and flexibility I needed over the years, but always gave me nudges when appropriate to get me moving in the right direction. Your guidance and advice has shaped who I am as a researcher/academician…thank you for all of the time you put up with me, and for caring so much about furthering my professional development. Thank you to Addie Middleton for your help with data collection (which made this study possible) and for being my comrade in navigating this PhD process. Thank you to Jessica Richardson for taking the time to help foster my interest in neuroimaging and stroke, and for teaching me your “mad skills” concerning imaging analyses. You truly were a driving force behind this study, and I am forever grateful for the time, guidance, and patience you showed me. Thank you to Jill Stewart for letting me take over your lab every few weeks and for helping me with the imaging analyses and all the hiccups encountered along the way. You are a great teacher, and I look forward to working with you more in the future. And thank you to Julius Fridriksson for allowing me to join his study so that I could collect data for this project, and to Leo Bonilha and Zeke Gleichgerrcht for their valuable input and advice concerning imaging analyses. iv ABSTRACT Great variability is seen in the clinical manifestation of and recovery from stroke. Structural abnormalities often extend beyond the infarction site, indirectly affecting nonlesioned areas which can further contribute to motor deficits. Advances in neuroimaging have enabled the examination of white matter integrity and anatomical connectivity within the brain. Evidence is limited, however, regarding the relationship between the structural integrity and connectivity of primary and secondary motor tracts/brain regions and chronic upper and (especially) lower extremity motor impairments post-stroke. Therefore, the current study examined the relationship between upper/lower extremity motor impairments and structural integrity (Aim 1) and connectivity (Aim 2) of motor-relevant brain pathways and regions in individuals with chronic stroke. Forty-three participants completed a comprehensive motor assessment, with MRI scanning performed within two days of behavioral testing. Nonparametric analyses were performed to examine the relationship between structural integrity and connectivity of motor-relevant brain regions and motor function. Regression analyses were performed to assess the amount of variance in upper/lower extremity motor performance explained by ipsilesional corticospinal tract (CST) and red nucleus (RN) integrity, as well as cortical connectivity of the three main brain regions of motor control [primary motor cortex (M1), premotor cortex, and supplementary motor area]. Results indicate that ipsilesional CST and RN structural integrity (as assessed by fractional anisotropy values) are both positively associated with chronic upper/lower extremity v motor function. Ipsilesional CST integrity, however, is a stronger predictor of chronic upper extremity motor function and grip strength post-stroke. Furthermore, cortical integrity and connectivity of ipsilesional M1 is associated with upper extremity motor function of the affected extremity and gait speed, with cortical disconnection of M1 being an independent predictor of chronic motor function. These findings highlight the importance of examining structural changes and cortical disconnection beyond the lesion site post-stroke. Such insight could enhance our understanding of the underlying factors contributing to motor impairments, and improve motor recovery prognosis and help with targeting therapeutic interventions. vi TABLE OF CONTENTS DEDICATION ....................................................................................................................... iii ACKNOWLEDGEMENTS ........................................................................................................ iv ABSTRACT ............................................................................................................................v LIST OF TABLES ....................................................................................................................x LIST OF FIGURES ................................................................................................................. xi LIST OF ABBREVIATIONS .................................................................................................... xii CHAPTER 1: INTRODUCTION ..................................................................................................1 CHAPTER 2: LITERATURE REVIEW ........................................................................................6 2.1 PATHOPHYSIOLOGY AND CLINICAL PRESENTATION OF STROKE ............................6 2.2 NEUROANATOMY OF MOTOR CONTROL ................................................................8 2.3 IMAGING AND STROKE .........................................................................................13 2.4 DIFFUSION TENSOR IMAGING ..............................................................................15 2.5 CORTICAL CONNECTIVITY AND NETWORK DISRUPTION ......................................21 2.6 DTI AND UPPER EXTREMITY MOTOR IMPAIRMENT/RECOVERY IN ACUTE STROKE .....................................................................................................22 2.7 DTI AND UPPER EXTREMITY MOTOR IMPAIRMENT/RECOVERY IN CHRONIC STROKE .................................................................................................26 2.8 DTI AND LOWER EXTREMITY/GAIT IMPAIRMENT IN STROKE ..............................35 2.9 DTI AND LOWER EXTREMITY/GAIT IMPAIRMENT IN OTHER PATIENT POPULATIONS .............................................................................................39 vii CHAPTER 3: METHODS ........................................................................................................48 3.1 RESEARCH DESIGN ..............................................................................................48 3.2 POWER ANALYSES ...............................................................................................48 3.3 PARTICIPANTS .....................................................................................................49 3.4 MOTOR ASSESSMENT ..........................................................................................50