DYNAMICS OF FUNCTIONAL CONNECTIVITY WITHIN CORTICAL MOTOR NETWORK DURING MOTOR LEARNING IN STROKE - CORRELATIONS WITH "TRUE" MOTOR RECOVERY

Abstract

Arm motor recovery after stroke is usually incomplete; six months after onset about two-thirds of patients suffer from arm motor impairment that significantly impacts the individual's activities of daily living. Thus, novel concepts beyond current strategies for arm motor rehabilitation after stroke are needed. An essential approach for this is to better understand whether motor learning-related neural changes in stroke are similar with those in healthy controls and how these neural changes relate to recovery of the pre-morbid movement pattern or "true" recovery. Abnormal task-related activation in primary and non-primary motor cortices has been a consistent finding in functional MRI studies of stroke. Disturbed functional network architecture, e.g., the influence that one motor area exerts over another, also impacts stroke recovery. The outcome measures chosen to evaluate recovery are also important for the interpretation of these brain changes. Thus, the long-range goal of this work was to longitudinally investigate the changes in cortical motor function at two levels, regional (micro-circuitry, regional activation) and network (macro-circuitry, functional connectivity), following an arm-focused motor training in chronic stroke survivors and how these brain changes relate to recovery of the pre-morbid movement pattern or "true" recovery. In the Chapter I, we reviewed the literature concerning the pathophysiology of stroke, neural substrates of motor control, and motor learning principles and neural substrates in healthy and pathological (stroke) brain. In the Chapter II, we examined the relationships between task-related motor activation and clinical and kinematic metrics of arm motor impairment in survivors of subcortical stroke. We found evidence that primary motor activation was significantly correlated to kinematic metrics of arm motor impairment, but not with clinical metrics. In the Chapter III, we longitudinally investigated the regional changes in motor-related activation (functional MRI) in primary and non-primary motor areas following an arm-focused motor training in stroke survivors and age-sex matched healthy controls. We demonstrated that similar changes in the motor areas contralateral to the trained arm were found with training in both stroke and healthy participants. We also demonstrated a significant increase in motor performance in both groups as well as a normalization of the correlations between bilateral motor activation and movement kinematics in participants with stroke. In the Chapter IV, we also investigated the changes in functional connectivity between primary and non-primary motor areas following an arm-focused motor training and how these changes correlate with "true" motor recovery. We demonstrated significant enhanced functional connectivity in motor areas contralateral to the trained hand (or ipsilesional), although no "normalization" of the inter-hemispheric inhibition following training in our survivors. We also showed a "normalization" of the relationships between cortical motor functional connectivity and movement kinematics. In the Chapter V, we concluded that the present dissertation work support the hypotheses that motor system is plastic at different levels, regional and network, even in the chronic stage of stroke and some of these changes are similar with those reported in healthy controls. Further, these changes provide a substrate for "true" recovery. These findings promote the use of neuroimaging and kinematic metrics to improve our understanding of the neural substrates underlying reorganization in remaining intact brain structures after stroke. Such an approach may further enable monitoring recovery or compensation based on this reorganization and evaluating new treatment regimes that assist motor recovery.