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

项目概要/摘要 脊髓损伤 (SCI) 是一种改变生活的事件，会导致长期的运动障碍。目前，没有 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、迈步和自主行走。然而，神经恢复机制诱导 人们对脊髓的电神经调节知之甚少。该项目将产生基于证据的 了解可能介导的神经回路的短期兴奋性和长期可塑性变化 SCS 引起的运动功能改善。 SCI 参与者和对照受试者将进行 30 分钟的腿部训练 使用控制计算机光标的非侵入性身体机器界面进行培训课程，并执行游戏- 例如使用随意运动和/或非侵入性经皮 SCS 的活动。我们将量化变化 通过比较运动诱发电位来量化皮质脊髓、网状脊髓和脊髓神经的兴奋性 分别由经颅磁刺激、StartReact 响应和 F 波响应引起 训练前和训练后。我们将确定（1）独立的神经兴奋性的短期变化 通过 SCS 和基于活动的培训实现，(2) 是否普遍使用特定任务培训 康复增强神经兴奋性的短期变化，以及（3）神经可塑性的长期变化 由 SCS 结合基于活动的训练对慢性 SCI 患者进行介导。清楚地了解 SCS 增强的神经机制及其如何通过残余皮质脊髓促进神经可塑性， 网状脊髓和脊柱连接将促进直接靶向的个性化疗法的发展 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 患有 SCI 的个体。在整个奖励期间，我将获得进行临床的新技能和专业知识 作为首席研究员进行研究。此外，我还将获得运动神经生理学评估方面的进一步培训 和感觉功能、皮质和脊髓可塑性评估、脊髓刺激、职业 开发和 R01 级资助写作。为了完成拟议的研究和培训，我聚集了 一个由世界级导师组成的多学科团队致力于我的成功。这次培训将建立在我的 以前作为实习生的临床和转化研究经验，最终为我提供了 建立独立研究计划并转变为独立 R01- 的知识和技能 资助的研究人员在理解和利用 SCI 后的神经可塑性方面引领全球进展。

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.