Facilitators of Motor Recovery Following Stroke

描述（由申请人提供）：在美国每年有350，000名中风幸存者，其中约200，000人患有持续性和致残性缺陷。中风恢复的机制尚不清楚，因此现有的治疗干预措施操作不当。近年来，调节性治疗（如强制使用或强制诱导治疗、药物治疗和细胞移植）已被用于卒中恢复;然而，这些治疗通常在选定的慢性卒中受试者组中进行研究，并且此类干预的适当时机在很大程度上是未知的，并且在大多数情况下不是基于解剖或生理信息。在这个建议中，我们结合联合收割机的脑成像技术，功能磁共振成像（fMRI），与电生理技术，经颅磁刺激（TMS），调查如何解剖和生理过程中相互作用的损伤后，在积极的恢复期，并确定其功能的重要性恢复。这种中风恢复的综合技术方法是本提案中最具创新性的方面，它使我们能够收集单独使用每种技术无法获得的数据。在目前的文献中，关于卒中后运动恢复期间，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，我们建议使用相结合的功能磁共振成像和经颅磁刺激的方法来解决这个特定的问题，并检查其他候选区域在运动恢复中风后。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恢复运动的激活模式，并将其与B）同侧和对侧皮质脊髓束的完整性以及使用TMS测量皮质皮质兴奋性，在实验2中，以确定是否抑制同侧感觉运动皮层激活与repetitiveTMS（rTMS）暂时影响运动性能的恢复手。我们假设，同侧运动皮层，虽然激活恢复的手的运动，是非功能性的，可能会阻碍恢复和其他激活的皮质区与良好的手功能的回报。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，在此期间，他们变得重要，将直接应用现有的，新的调节疗法的发展，以改善结果，减少残疾的中风幸存者。

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.