Rehabilitation from Spinal Cord Injury Using Targeted, Activity-Dependent Intraspinal Stimulation

使用有针对性的活动依赖性椎管内刺激来康复脊髓损伤

• 批准号: 9381549
• 负责人: Steve I Perlmutter
• 金额: $ 49.13万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9381549
• 关键词: Address; Anatomy; Animal Model; Behavior; Behavioral; Brain; Cerebral cortex; Cervical spinal cord injury; Chronic; Clinical; Clinical Trials; Complement; Contusions; Data; Dependence; Development; Effectiveness; Electric Stimulation; Electrodes; Electrophysiology (science); Forelimb; Foundations; Future; Genetic; Goals; Hand; Intervention; Investigation; Knowledge; Methods; Modeling; Motor; Motor Pathways; Movement; Muscle; Natural regeneration; Nature; Nervous system structure; Neural Pathways; Neuronal Plasticity; Neurons; Pathway interactions; Performance; Physical Function; Physical Rehabilitation; Physiological; Protocols documentation; Quality of life; Rattus; Recovery; Recovery of Function; Rehabilitation therapy; Residual state; Signal Transduction; Site; Spinal; Spinal Injuries; Spinal cord injury; Stimulus; Surface; Synaptic plasticity; System; Technology; Testing; Therapy Clinical Trials; Transplantation; Use Effectiveness; Volition; arm; base; brain computer interface; clinical practice; combinatorial; design; effective therapy; flexibility; human subject; improved; improved functioning; motor deficit; motor recovery; nervous system disorder; neural circuit; neuromechanism; neuronal survival; neuroprosthesis; novel; pre-clinical; relative effectiveness; spinal pathway; synaptogenesis; translation to humans

Project Summary The objective of the proposed project is to develop a neuroprosthetic therapy that uses targeted, activity-dependent spinal stimulation to improve arm and hand motor recovery after cervical spinal cord injury (SCI). The project seeks to advance clinical practice through the use of brain-computer-interface technology to harness physiological mechanisms of neural plasticity. Motor deficits severely impact the quality of life of people with SCI, yet current treatments produce limited improvements in movement abilities. Recent clinical and experimental evidence suggests that electrical stimulation of the nervous system can be an effective therapy for a variety of neurological disorders. This preclinical project will evaluate a novel application of electrical stimulation for rehabilitation of forelimb motor deficits in a rat model of SCI. The strategy is designed to enhance the function of spared neural pathways by directing Hebbian plasticity through targeted stimulation of volitionally activated neural circuits. Results will lay the foundation for a future clinical trial using spinal stimulation in human subjects with SCI. Preliminary data demonstrate the effectiveness of one-channel, intraspinal stimulation triggered by activity of a forelimb muscle to improve motor performance in rats with chronic SCI. Specific Aim 1 seeks a) to develop a multi-channel intervention to enhance functional recovery and b) to characterize the interplay between stimulation and physical rehabilitation in order to establish principles for combining the therapies. Specific Aim 2 will determine the relative effectiveness of ECoG vs. EMG as a triggering signal for facilitating behavioral recovery. Specific Aim 3 begins an investigation of the mechanisms of action of the intervention to suggest refinements and combinatorial therapies to facilitate further recovery.

项目摘要 拟议项目的目标是开发一种神经修复疗法， 有针对性的活动依赖性脊髓刺激，以改善手臂和手部运动恢复， 颈脊髓损伤（SCI）。该项目旨在通过使用 利用神经可塑性的生理机制。 运动缺陷严重影响SCI患者的生活质量，但目前的治疗方法 对运动能力的改善有限。最近的临床和实验证据 表明，神经系统的电刺激可以是一种有效的治疗方法， 各种神经系统疾病该临床前项目将评估一种新的应用， 电刺激用于SCI大鼠模型中前肢运动缺陷的康复。的 策略的目的是通过指导Hebbian增强备用神经通路的功能， 可塑性通过有针对性的刺激意志激活神经回路。结果将奠定 为将来在SCI患者中使用脊髓刺激进行临床试验奠定了基础。 初步数据证明了单通道椎管内刺激的有效性 由前肢肌肉活动触发，以改善慢性SCI大鼠的运动表现。 具体目标1寻求a）发展多渠道干预，以促进功能恢复 和B）表征刺激和身体康复之间的相互作用， 制定联合治疗的原则。具体目标2将确定相对 ECoG与EMG作为促进行为恢复的触发信号的有效性。 具体目标3开始调查干预措施的作用机制， 建议改进和组合疗法以促进进一步恢复。