Facilitators of Motor Recovery Following Stroke

描述（由申请人提供）：在美国每年35万中风幸存者中，大约20万人有持续的残疾缺陷。中风恢复的机制尚不清楚，因此现有的治疗干预措施很难控制。近年来，强制使用或限制性治疗、药物治疗和细胞移植等调节疗法已被用于中风恢复；然而，这些疗法通常是在选定的慢性中风患者群体中进行研究的，这些干预的适当时机在很大程度上是未知的，在大多数情况下，不是基于解剖或生理信息。在本研究中，我们将脑成像技术——功能性磁共振成像（fMRI）与电生理技术——经颅磁刺激（TMS）相结合，研究损伤后活跃恢复期的解剖和生理过程如何相互作用，并确定它们对恢复的功能重要性。这种综合技术方法是该方案中最具创新性的方面，它允许我们收集单独使用每种技术无法获得的数据。在目前的文献中，关于中风后运动恢复过程中，同侧未受影响的感觉运动皮层及其未交叉的皮质脊髓束是否会取代对侧受影响的感觉运动皮层和/或皮质脊髓束的作用，存在相互矛盾的证据。在两个连续的实验中，我们建议使用功能磁共振成像和经颅磁刺激相结合的方法来解决这个特定的问题，并检查中风后运动恢复的其他候选区域。我们的具体目标是，在实验一中，确定在四个临床定义的恢复阶段a)使用fMRI确定恢复运动的激活模式并将其与b)使用TMS测量单侧和对侧皮质脊髓束的完整性以及皮质皮质兴奋性的测量相关联；在实验二中，确定重复TMS （rTMS）抑制同侧感觉运动皮质激活是否会暂时影响恢复手的运动表现。我们假设同侧运动皮质虽然在手部恢复时被激活，但它是无功能的，可能会阻碍康复，而其他激活的皮质区域与手部良好功能的恢复有关。确定运动网络的关键区域和相互作用，使恢复和关键时间点成为重要的，将指导现有的应用和新的调节疗法的发展，以改善结果和减少中风幸存者的残疾。

DESCRIPTION (provided by applicant): Of the 350,000 people surviving stroke each year in the United States, approximately 200,000 have persistent and disabling deficits. The mechanisms of stroke recovery are unknown and therefore poorly manipulated by existing therapeutic interventions. Modulatory therapies such as forced-use or constraintinduced therapy, pharmaco-therapy, and cell transplantation have been employed in stroke recovery over recent years; however, these therapies are commonly investigated in selected groups of chronic stroke subjects and the appropriate timing for such interventions is largely unknown and in most cases is not based on anatomic or physiologic information. In this proposal, we combine a brain imaging technique, functional magnetic resonance imaging (fMRI), with an electrophysiological technique, transcranial magnetic stimulation (TMS), to investigate how the anatomical and physiological processes interact following injury during the active recovery period and to determine their functional importance for recovery. This combined technology approach to stroke recovery is the most innovative aspect of this proposal and it permits us to gather data unavailable by employing each technology alone. In the current literature there is contradictory evidence over whether following stroke, during motor recovery, the ipsilateral, unaffected, sensorimotor cortex and its uncrossed corticospinal tract take over the role of the contralateral, affected, sensorimotor cortex and/or corticospinal tract. In two sequential experiments we propose to use the combined fMRI and TMS approach to address this specific question and to examine other candidate regions in motor recovery following stroke. Our specific aims are, in experiment one, to determine at four clinically-defined stages of recovery a) the activation pattern of recovering movements using fMRI and correlate it to b) the integrity of ipsi- and contralateral corticospinal tracts and the measures of cortico-cortico excitability using TMS and in experiment 2, to determine whether inhibition of the ipsilateral sensorimotor cortex activation with repetitiveTMS (rTMS) temporarily affects motor performance in the recovering hand. We hypothesize that ipsilateral motor cortex, although activated on movement of the recovering hand, is non-functional and perhaps hinders recovery and that other activated cortical areas are associated with return of good hand function. Identifying the critical areas and interactions of the motor network that enable recovery and the critical timepoints during which they become important, will direct the application of existing, and the development of new modulatory therapies to improve outcome and reduce disabilities for stroke survivors.