Enhancement of hand motor function after cervical spinal cord injury

描述（由申请人提供）： 手部运动功能障碍是颈脊髓损伤（SCI）退伍军人的主要缺陷。虽然康复干预在改善手部运动功能方面取得了成功，但其总体效果仍然有限。本研究的目的是探讨颈脊髓损伤后手部运动控制的中枢神经系统通路的生理学，并通过非侵入性脑刺激和运动训练促进手部运动的恢复。我们专注于两个基本方面涉及手的运动功能：一个精确的抓地力和手腕弯曲和伸展。这些是我们大多数日常生活活动的必要技能;因此，我们的研究结果可能会直接影响退伍军人及其照顾者的生活质量， 提高他们的独立性和护理水平。 我们将研究运动皮层和脊髓运动神经元对颈椎脊髓损伤后精确抓握和手腕运动肌肉控制的贡献（目的1）。经颅磁刺激（TMS）将用于检查针对手指和手腕肌肉的皮质脊髓和皮质内通路的传输，而外周神经刺激将用于评估手指和手腕运动神经元的兴奋性。这些研究将确定SCI对控制手部运动的CNS通路的影响。然后，我们建议通过使用高频无创重复经颅磁刺激（rTMS）和运动训练（目标2）的新协议，以提高手部运动功能的恢复。首先，rTMS将以任务依赖的方式在精确抓握和手腕运动期间使用，以诱导皮质可塑性并增强手部肌肉的随意输出。 第二，rTMS将在涉及精确抓握和手腕运动的视觉运动训练任务期间以任务依赖的方式应用。这些独特的方法旨在促进功能相关的手部运动过程中的神经可塑性，这是以前没有做过的。 拟议的研究将基础科学人类研究和转化神经科学紧密结合起来。无创性脑刺激的新方法可能为SCI后恢复手部运动功能开辟新的方向。缺乏广泛接受的治疗手运动障碍的退伍军人颈椎脊髓损伤和有限的行为收益目前的干预措施强调了这些调查的重要性。 公共卫生相关性： 手运动功能在很大程度上被破坏的退伍军人与颈椎脊髓损伤。这对日常生活活动产生了巨大的影响。本提案将研究颈脊髓损伤后控制手部运动功能的途径的生理变化，以及通过将非侵入性重复脑刺激与运动训练相结合来增强手部运动功能恢复的新方法。手功能受损是中风、肌萎缩侧索硬化症、多发性硬化症和其他运动障碍后的主要问题，因此，我们的工作也可能与CNS其他病变的个体相关。

DESCRIPTION (provided by applicant): Impairment in hand motor function is a major deficit in veterans with cervical spinal cord injury (SCI). While rehabilitative interventions have shown success in improving aspects of hand motor function their overall effects remain limited. The goals of this proposal are to examine the physiology of CNS pathways contributing to the control of hand movements after cervical SCI, and to promote the recovery of hand movements by using non-invasive brain stimulation and motor training. We focus on two basic aspects involved in hand motor function: a precision grip and wrist flexion and extension. These are necessary skills for most of our daily-life activities; therefore, our results may directly impact the quality of life for veterans and their caregivers by enhancing their independence and level of care. We will investigate the contribution of the motor cortex and spinal motoneurons to the control of muscles involved in precision grip and wrist movements after cervical SCI (Aim 1). Transcranial magnetic stimulation (TMS) will be used to examine transmission in corticospinal and intracortical pathways targeting finger and wrist muscles, whereas peripheral nerve stimulation will be used to assess the excitability of finger and wrist motoneurons. These studies will identify the effects of SCI on CNS pathways controlling hand movements. Then, we propose to enhance the recovery of hand motor function by using novel protocols of high frequency non-invasive repetitive TMS (rTMS) and motor training (Aim 2). First, rTMS will be used during precision grip and wrist movements in a task- dependent manner to induce cortical plasticity and enhance voluntary output of hand muscles. Second, rTMS will be applied in a task-dependent manner during a visuo-motor training task that involves precision grip and wrist movements. These unique approaches aim at promoting neuroplasticity during functionally relevant hand movements, which has not been done before. The proposed studies tightly couple basic scientific human research and translational neuroscience. The novel approaches of non-invasive brain stimulation may open new directions for restoring hand motor function after SCI. The absence of well-accepted treatments for hand motor impairments for veterans with cervical SCI and the limited behavioral gains of present interventions underline the importance of these investigations. PUBLIC HEALTH RELEVANCE: Hand motor function is largely disrupted in Veterans with cervical SCI. This has tremendous impact on daily-life activities. This proposal will examine physiological changes in pathways controlling hand motor function after cervical SCI and novel methods to enhance the recovery of hand motor function by combining non-invasive repetitive brain stimulation with motor training. Impairment in hand function is a major problem after stroke, amyotrophic lateral sclerosis, multiple sclerosis, and other motor disorders, therefore, our work may also be relevant for individuals with other lesions of the CNS.