Acquisition and Retention of Locomotor Adaptations after Stroke

描述（由申请人提供）：运动学习是康复干预治疗中风等衰弱性神经系统疾病患者的基础。现在已经知道小脑是运动适应和运动学习所必需的。运动皮层也参与运动学习，但其具体作用尚不清楚。最近的研究表明，运动皮层可能更多地参与运动学习的巩固和/或保留阶段，而不是最初的习得阶段。目前尚不清楚是否涉及运动皮质的中风患者在保留新获得的运动适应方面存在缺陷。总的来说，本研究的目的是确定涉及初级运动输出系统的单侧中风对人类新学习的视觉运动步行适应的保留的影响。运动捕捉、肌电图和经颅磁刺激（TMS）将分别用于记录肢体运动和测量和调节皮质脊髓兴奋性。在Aim 1中，行走过程中的视觉反馈将被改变，以诱导健康和中风影响的成年人的一种新的步态模式，在中风受试者中，这种步态模式旨在改善双腿之间单肢支撑持续时间的对称性。新的步行方式的初始适应和保持将在几个时间段内进行测量和比较。中风患者的记忆保留能力下降，但适应能力相对完整。在Aim 2中，低频抑制性重复颅磁刺激（rTMS）将应用于中风患者行走前未受损半球的初级运动皮层（M1）。将测量rTMS对视觉运动步行适应的获得和保留的影响，并与一组接受假刺激的脑卒中受试者进行比较。单脉冲经颅磁刺激将用于测量经颅磁刺激前后皮质脊髓兴奋性的变化。我们预测，对未受损M1的抑制性rTMS将改善卒中受试者的步行适应保留，并将与受损M1的去抑制有关。我们还期望发现rTMS的益处水平随病变位置而变化。研究结果将有助于确定涉及初级运动输出系统的中风患者在新适应的行走模式的习得和/或保留方面是否存在缺陷，以及这种缺陷是否可以通过rTMS暂时改善。这项工作特别重要，因为1)它将有助于确定运动皮层在运动适应的获得和/或保留中的作用，2)它将支持或否定所提出的机制，即未受损半球的过强经胼胝体抑制是中风患者运动损伤的来源，3)它可能导致新疗法的发展，以增强中风所致运动障碍患者的运动学习和保留。

DESCRIPTION (provided by applicant): Motor learning forms a foundation for rehabilitation interventions to treat patients with debilitating neurological disorders such as stroke. It is now known that the cerebellum is required for motor adaptations and motor learning. The motor cortex is also involved in motor learning, but its specific role is less clear. Recent studies indicate that the motor cortex may be more involved in the consolidation and/or retention phases of motor learning than in the initial acquisition. It is not known whether individuals with stroke involving the motor cortex have deficits in retention of newly acquired motor adaptations. Broadly, the purpose of this research is to determine the effects of unilateral stroke involving the primary motor output system on retention of a newly learned visuomotor walking adaptation in humans. Motion capture, electromyography and transcranial magnetic stimulation (TMS) will be used to record limb movements and to measure and modulate corticospinal excitability, respectively. In Aim 1, visual feedback during walking will be altered to induce a novel gait pattern in healthy and stroke-affected adults that, in stroke subjects, is designed to improve symmetry of single limb support durations between the legs. Initial adaptation and retention of the new walking pattern will be measured and compared across groups at several time periods. Subject with stroke are expected to show reduced retention but relatively intact adaptation. In Aim 2, low frequency inhibitory repetitive TMS (rTMS) will be applied over the primary motor cortex (M1) of the non- lesioned hemisphere in individuals with stroke prior to walking. Effects of rTMS on the acquisition and retention of the visuomotor walking adaptation will be measured and compared to a group of stroke subjects receiving sham stimulation. Single pulse TMS will be used to measure changes in corticospinal excitability before and after rTMS. We predict that inhibitory rTMS to the non-lesioned M1 will improve retention of the walking adaptation in stroke subjects, and will be associated with disinhibition of the lesioned M1. We also expect to find that the level of benefit from rTMS varies with lesion location. Results from the proposed aims will help determine whether individuals with stroke involving the primary motor output system have deficits in acquisition and/or retention of newly adapted walking patterns and whether this deficit can be temporarily improved using rTMS. This work is particularly important because 1) it will help determine the role of the motor cortex in acquisition and/or retention of motor adaptations, 2) it will support or refute the proposed mechanism of overly strong transcallosal inhibition from the non-lesioned hemisphere as a source of motor impairment in patients with stroke, and 3) it may lead to the development of novel therapies to enhance motor learning and retention in patients with motor disability due to stroke. PUBLIC HEALTH RELEVANCE: Results from these studies will provide novel insights into brain mechanisms of impaired motor learning following stroke. Importantly, findings are expected to help lead to the development of new rehabilitation interventions to enhance motor learning of locomotor patterns in patients with stroke. Thus, this work will have broad impact on public heath, as stroke is a leading cause of long-term disability and leaves many of its victims unable to walk without assistance.