Neural plasticity by spinal cord stimulation and training in people with spinal cord injury

项目总结/摘要 脊髓损伤（SCI）是一种改变生活的事件，导致长期的运动障碍。目前尚无 治愈瘫痪脊髓电刺激（SCS）结合运动训练可以恢复姿势 SCI患者的控制、行走和自主行走。然而，神经恢复机制诱导 对脊髓的电神经调节知之甚少。该项目将产生基于证据的 了解神经回路的短期兴奋性和长期可塑性的变化， SCS诱导的运动功能改善。SCI受试者和对照受试者将进行30分钟的腿部训练， 使用非侵入式身体-机器界面控制计算机光标进行训练，并进行游戏- 例如使用自主运动和/或非侵入性经皮SCS的活动。我们将量化 皮质脊髓、网状脊髓和脊髓神经兴奋性将通过比较运动诱发电位来定量 分别由经颅磁刺激、StartReact反应和F波反应引起 训练前后。我们将确定（1）神经兴奋性的短期变化， （2）特定任务培训是否常用在 康复治疗可增强神经兴奋性的短期变化;（3）神经可塑性的长期变化 通过SCS与基于活动的训练相结合介导的慢性SCI患者。清楚地了解 SCS增强的神经机制以及它们如何通过残留的皮质脊髓， 网状脊髓和脊髓连接将促进个性化治疗的发展， 这些回路的特定兴奋性和可塑性状态，以促进和增强功能恢复， SCI患者。在整个奖励期间，我将获得新的技能和专业知识，在进行临床 作为首席研究员。此外，我将获得进一步的培训，在神经生理学评估的运动 和感觉功能，皮质和脊髓可塑性评估，脊髓刺激，职业生涯 开发和R 01级赠款写作。为了完成拟议的研究和培训，我已召集 一个由世界级导师组成的多学科团队，他们致力于我的成功。这次培训将建立在我的 作为实习生，我以前在临床和转化研究方面的经验，最终为我提供了 知识和技能，以建立一个独立的研究计划，并过渡到一个独立的R 01- 资助的研究人员领导全球对SCI后神经可塑性的理解和利用。

PROJECT SUMMARY/ABSTRACT Spinal cord injury (SCI) is a life-altering event that leads to long-lasting motor impairment. Currently, there is no cure for paralysis. Electrical spinal cord stimulation (SCS) combined with exercise training can restore posture control, stepping, and voluntary walking in humans with SCI. However, the neurorecovery mechanisms induced by electrical neuromodulation of the spinal cord are poorly understood. This project will generate evidence-based knowledge of changes in short-term excitability and long-term plasticity of the neural circuits that may mediate SCS-induced improvements in motor function. Participants with SCI and control subjects will perform 30-min leg training sessions with a non-invasive body-machine interface controlling a computer cursor, and perform game- like activities using voluntary movements and/or non-invasive transcutaneous SCS. We will quantify changes in corticospinal, reticulospinal, and spinal neural excitability will be quantified by comparing motor-evoked potentials elicited by transcranial magnetic stimulation, the StartReact response, and the F-wave responses respectively before and after training. We will determine (1) short-term changes in neural excitability that are independently enabled by SCS and activity-based training, (2) whether task-specific training used commonly used in rehabilitation enhances short-term changes in neural excitability, and (3) long-term changes in neural plasticity mediated by SCS combined with activity-based training in individuals with chronic SCI. A clear understanding of SCS-enhanced neural mechanisms and how they promote neural plasticity through residual corticospinal, reticulospinal, and spinal connections will promote the development of personalized therapies that directly target the specific excitability and plasticity states of these circuits to promote and enhance functional recovery in individuals with SCI. Throughout the award period, I will obtain new skills and expertise in conducting clinical studies as the lead investigator. In addition, I will gain further training in neurophysiological evaluations of motor and sensory function, evaluation of cortical and spinal cord plasticity, spinal cord stimulation, career development, and R01-level grant writing. To accomplish the proposed research and training, I have assembled a multi-disciplinary team of world class mentors who are committed to my success. This training will build on my previous experience in clinical and translational research as a trainee and ultimately provide me with the knowledge and skillset to establish an independent research program and transition into an independent R01- funded investigator leading global progress in understanding and exploiting neuroplasticity after SCI.