Brain areas that control reaching movements after stroke: Task-relevant connectivity and movement-synchronized brain stimulation

点击翻译按钮获取中文摘要

As stroke is a leading cause of disability among veterans, there is a compelling need to develop treatments that improve motor ability after a stroke affects those brain networks relevant to motor function. Our goal is to improve motor function after stroke through methods that combine brain stimulation with practice. To advance this goal we need an understanding of the network changes that underlie recovery of useful motor behaviors such as reaching. Non- primary cortical motor areas have been shown to have strong connections with other motor areas, including the primary motor cortex, and there is some evidence that their functional role changes after stroke. We and others have also demonstrated the ability to influence reaching behavior with focal cortical stimulation, and to influence the cortical representation of reaching movement through the combination of cortical stimulation with reaching practice. We will use this new knowledge and increase our understanding of brain network changes and the effects of brain stimulation and practice by completing the following three aims: 1. Quantify effects of disrupting activity in PMd and PMv in each hemisphere during reaching tasks in participants with and without capsular stroke. The functional role of each region will be assessed through the effects of brief trains of repetitive transcranial magnetic stimulation in the dorsal and ventral premotor areas of each hemisphere during reaching tasks in human participants with and without capsular stroke. The specifics of white matter damage will influence which region on each side affects connectivity most. 2. Quantify connectivity with M1 and other motor regions in human participants with and without capsular stroke. This will be assessed by resting state & task-related connectivity using fMRI, and will demonstrate differences between the three types of functional connectivity measures: TMS regional effects on motor output, resting state fMRI, and dynamic causal models of task-related fMRI. The relationship between motor function and functional connectivity will therefore have been tested. 3. Evaluate the effects of movement- synchronized TMS of the most facilitatory region on the effects of practice on motor output and behavioral performance. TMS of the most functionally relevant premotor region will be synchronized with practice of the affected upper extremity. An innovative feature of this work is the study of internal capsule stroke, which is a more homogeneous and appropriate population than the overall set of stroke types that affect movement, which has a great deal of variety. These findings will allow us to formulate clear hypotheses about which premotor area should be modulated after stroke, and when, in the context of movement practice. We will be able to design a novel treatment protocol that delivers precisely timed stimulation during practice of reaching movements.