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

项目摘要/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。脊髓电刺激结合运动训练可恢复体位 患有脊髓损伤的人类的控制、步行和自愿行走。然而，诱导的神经康复机制 对脊髓的电神经调节知之甚少。这个项目将产生基于证据的 了解可能调节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。有脊髓损伤的参与者和对照受试者将进行30分钟的腿部运动 通过控制计算机光标的非侵入性体机接口进行训练，并执行游戏- 如使用自主运动和/或非侵入性经皮SCS的活动。我们将量化这些变化 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进行量化。 经颅磁刺激、StartReact反应和F波反应 训练前后。我们将确定(1)神经兴奋性的短期变化 通过SCS和基于活动的培训实现，(2)任务特定培训是否在 康复增强了神经兴奋性的短期变化，以及(3)神经可塑性的长期变化 SCS结合活动训练对慢性脊髓损伤患者的干预作用。对……的清醒认识 SCS增强的神经机制及其如何通过残留的皮质脊髓促进神经可塑性， 网状脊髓和脊柱连接将促进个性化治疗的发展，直接针对 这些环路促进和增强功能恢复的特异性兴奋性和可塑性状态 患有脊髓损伤的个体。在整个获奖期内，我将获得临床指导方面的新技能和专业知识 作为首席调查员进行研究。此外，我还将接受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，职业生涯 发展，和R01级拨款撰写。为了完成拟议的研究和培训，我召集了 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 作为实习生之前在临床和翻译研究方面的经验，并最终为我提供了 建立独立研究计划并过渡到独立R01的知识和技能- 在理解和开发脊髓损伤后神经可塑性方面领导全球进展的基金研究员。

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.