Flexor Dysfunction Following Unilateral Transient Ischemic Brain Injury Is Associated with Impaired Locomotor Rhythmicity

Abstract

Flexor Dysfunction Following Unilateral Transient Ischemic Brain Injury Is Associated with Impaired Locomotor Rhythmicity Kiril Tuntevski Functional motor deficits in hemiplegia after stroke are predominately associated with flexor muscle impairments in animal models of ischemic brain injury, as well as in clinical findings. Rehabilitative interventions often employ various means of retraining a maladapted central pattern generator for locomotion. Yet, holistic modeling of the central pattern generator, as well as applications of such studies, are currently scarce. Most modeling studies rely on cellular neural models of the intrinsic spinal connectivity governing ipsilateral flexor-extensor, as well as contralateral coupling inherent in the spinal cord. Models that attempt to capture the general behavior of motor neuronal populations, as well as the different modes of driving their oscillatory function in vivo is lacking in contemporary literature. This study aims at generating a holistic model of flexor and extensor function as a whole, and seeks to evaluate the parametric coupling of ipsilateral and contralateral half-center coupling through the means of generating an ordinary differential equation representative of asymmetric central pattern generator models of varying coupling architectures. The results of this study suggest that the mathematical predictions of the locomotor centers which drive the dorsiflexion phase of locomotion are correlated with the denervation-type atrophy response of hemiparetic dorsiflexor muscles, as well as their spatiotemporal activity dysfunction during in vivo locomotion on a novel precise foot placement task. Moreover, the hemiplegic solutions were found to lie in proximity to an alternative task-space solution, by which a hemiplegic strategy could be readapted in order to produce healthy output. The results revealed that there are multiple strategies of retraining hemiplegic solutions of the CPG. This solution may modify the hemiparetic locomotor pattern into a healthy output by manipulating inter-integrator couplings which are not damaged by damage to the descending drives. Ultimately, some modeling experiments will demonstrate that the increased reliance on intrinsic connectivity increases the stability of the output, rendering it resistant to perturbations originating from extrinsic inputs to the pattern generating center iii DEDICATIONS To health. To life. To my family. Special thanks to the rodent surgery core led by Xuefang Ren and Heng Hu for assistance in training as well as surgical support. Sincere gratitude goes to the Muscle Biology laboratory of Stephen E. Alway. v List of Tables viii List of Figures ix List of Multimedia Files xi List of Symbols and Abbreviations xii xi LIST OF MULTIMEDIA FILES Multimedia File 1. CPG7a.m Multimedia File 2. CPG7a_optimize.m Multimedia File 3. Statistical_Analysis.m Multimedia File 4. Cranial_Implant.skb xii LIST OF SYMBOLS AND ABBREVIATIONS CNScentral nervous system BBBblood-brain barrier BBB Scale-Basso-Beatie-Bresnahan locomotor ...