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

脊髓损伤患者脊髓刺激和训练的神经可塑性

• 批准号: 10506190
• 负责人: Ismael Seanez
• 金额: $ 20.96万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10506190
• 关键词: Award; Chronic; Clinical; Clinical Research; Computers; Cortical Cord; Corticospinal Tracts; Cross-Over Studies; Data; Development; Evaluation; Event; Exercise; Funding; Goals; Grant; Human; Impairment; Individual; Injury; Joints; Knowledge; Lead; Leg; Life; Magnetism; Mediating; Mentors; Methods; Motor; Motor Evoked Potentials; Movement; Musculoskeletal Equilibrium; Neuraxis; Neuronal Plasticity; Neurostimulation procedures of spinal cord tissue; Outcome; Paralysed; Participant; Patients; Persons; Phase; Randomized Controlled Trials; Reaction Time; Recovery; Recovery of Function; Rehabilitation therapy; Reporting; Research; Research Design; Research Personnel; Research Training; Residual state; Rodent Model; Sensory; Spinal; Spinal Cord; Spinal Cord Plasticity; Spinal cord injury; Structure; Synapses; Techniques; Testing; Time; Training; Transcranial magnetic stimulation; Translating; Translational Research; Walking; Work; Writing; auditory stimulus; base; body-machine interface; career development; evidence base; exercise training; experience; functional improvement; improved; joint mobilization; motor control; motor function improvement; motor impairment; multidisciplinary; neural circuit; neurological rehabilitation; neuromechanism; neurophysiology; neuroregulation; novel; open label; personalized medicine; physical therapist; programs; rehabilitation strategy; relating to nervous system; response; reticulospinal tract; skills; strength training; success

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.

项目摘要/摘要 脊髓损伤（SCI）是一个改变人生的事件，导致运动障碍。目前，没有 治愈麻痹。电脊髓刺激（SCS）与运动训练相结合可以恢复姿势 控制，步进和自愿在人类中行走。但是，神经记录机制诱导了 通过对脊髓的电神经调节的理解很少。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的变化 SCS引起的运动功能改善。具有SCI和控制科目的参与者将表现30分钟的腿 通过控制计算机光标的非侵入性车身接口进行训练，并执行游戏 - 就像使用自愿运动和/或非侵入性经皮SC的活动一样。我们将量化更改 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量化 分别通过经颅磁刺激，StarTreact反应和F波响应引起 训练前后。我们将确定（1）独立的神经兴奋性的短期变化 由SCS和基于活动的培训启用，（2）是否使用 康复增强了神经兴奋性的短期变化，（3）神经可塑性的长期变化 由SCS介导的慢性SCI患者中的基于活动的培训。对 SCS增强的神经机制及其如何通过残留皮质脊髓来促进神经可塑性， 网状脊髓和脊柱连接将促进直接针对的个性化疗法的开发 这些电路的特定兴奋性和可塑性状态，以促进和增强功能恢复 患有科幻的人。在整个奖励期间，我将获得进行临床的新技能和专业知识 研究作为主要研究者。此外，我还将在运动的神经生理学评估中进一步培训 以及感觉功能，皮质和脊髓可塑性的评估，脊髓刺激，职业 开发和R01级赠款写作。为了完成拟议的研究和培训，我已经组装了 致力于我成功的世界一流导师的多学科团队。这种培训将基于我的 以前在临床和转化研究方面的经验，是学员，最终为我提供了 知识和技能以建立独立的研究计划并过渡到独立的R01- 在SCI之后，资助的研究人员在理解和利用神经可塑性方面的全球领先进步。