Acquisition and Retention of Locomotor Adaptations after Stroke

描述(由申请人提供)：运动学习构成康复干预的基础，用于治疗中风等衰弱神经疾病患者。现在已经知道，小脑是运动适应和运动学习所必需的。运动皮质也参与运动学习，但其具体作用尚不清楚。最近的研究表明，运动皮质可能更多地参与了运动学习的巩固和/或保持阶段，而不是最初的习得。目前尚不清楚中风涉及运动皮质的个体是否在保持新获得的运动适应方面存在缺陷。总的来说，这项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到的视觉运动行走适应的保留的影响。运动捕捉、肌电和经颅磁刺激(TMS)将分别用于记录肢体运动和测量和调节皮质脊髓的兴奋性。在目标1中，行走过程中的视觉反馈将被改变，以在健康和中风患者中诱导出一种新的步态模式，在中风受试者中，这种模式旨在改善双腿之间单肢支撑持续时间的对称性。新步行模式的初始适应和保持将在几个时间段跨组进行测量和比较。中风受试者预计会表现出较少的保留，但相对完整的适应。在目标2中，低频抑制性重复TMS(RTMS)将在卒中患者步行前在非病变大脑半球的初级运动皮质(M1)上进行。将测量rTMS对视觉运动行走适应的获得和保持的影响，并将其与接受假刺激的一组中风受试者进行比较。单脉冲TMS将用于测量rTMS前后皮质脊髓兴奋性的变化。我们预测，对非病变M1的抑制rTMS将改善卒中患者步行适应的保持，并将与病变M1的去抑制有关。我们还期望发现rTMS的益处水平因病变部位而异。拟议目标的结果将有助于确定涉及初级运动输出系统的中风患者在获得和/或保留新适应的行走模式方面是否存在缺陷，以及这种缺陷是否可以通过使用rTMS暂时改善。这项工作之所以特别重要，是因为1)它将有助于确定运动皮质在运动适应的获得和/或保持中的作用；2)它将支持或驳斥非损伤性大脑半球过强的经颧骨抑制作为中风患者运动障碍来源的机制；3)它可能导致开发新的治疗方法，以增强中风运动残疾患者的运动学习和保持能力。 公共卫生相关性：这些研究的结果将为中风后运动学习障碍的大脑机制提供新的见解。重要的是，这些发现有望帮助开发新的康复干预措施，以加强中风患者对运动模式的运动学习。因此，这项工作将对公众健康产生广泛影响，因为中风是导致长期残疾的主要原因，并使许多患者在没有帮助的情况下无法行走。

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.