Activity-Dependent Spinal Stimulation for Motor Recovery After Spinal Cord Injury

脊髓损伤后运动恢复的活动依赖性脊髓刺激

• 批准号: 8869898
• 负责人: Steve I Perlmutter
• 金额: $ 50.7万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8869898
• 关键词: Behavior; Behavioral; Brain; Cervical spinal cord injury; Chronic; Clinical; Clinical Trials; Complement; Data; Dependence; Devices; Early treatment; Effectiveness; Electric Stimulation; Electrocorticogram; Electrodes; Forelimb; Foundations; Future; Genetic; Goals; Hand; Health; Human; Injury; Intervention; Investigation; Knowledge; Lesion; Modeling; Motor; Movement; Muscle; Nature; Nervous system structure; Neural Pathways; Neuronal Plasticity; Neurons; Neurostimulation procedures of spinal cord tissue; Outcome; Pathway interactions; Performance; Pharmacological Treatment; Phase; Physical Rehabilitation; Physiological; Pilot Projects; Protocols documentation; Quality of life; Rattus; Recovery; Recovery of Function; Reflex action; Regulation; Rehabilitation therapy; Relative (related person); Serotonin; Signal Transduction; Site; Source; Spinal; Spinal Cord; Spinal cord injury; Stimulus; Structure; Surface; Synapses; Synaptic plasticity; System; Technology; Testing; Therapy Clinical Trials; Time; Training; Transplantation; arm; axon regeneration; brain computer interface; clinical application; clinical practice; combinatorial; design; effective intervention; effective therapy; human subject; improved; motor deficit; nerve supply; nervous system disorder; neural circuit; neuronal survival; neuroprosthesis; novel; postsynaptic; pre-clinical; presynaptic; spinal pathway; success; synaptogenesis

DESCRIPTION (provided by applicant): The objective of the proposed project is to develop a neuroprosthetic device 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 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 subjets 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 to optimize the one-channel intervention by exploring the use of electrocorticography signals to trigger stimulation rather than muscle activity, and of less invasive surface stimulation of the spinal cord. A new electrode technology will be deployed for cortical recording and surface stimulation. Specific Aim 2 will develop multi-channel stimulation to extend the capacity of the therapy. Specific Aim 3 will determine if the therapy can produce further recovery if introduced during the subacute phase of SCI. Specific Aim 4 begins an investigation of the mechanisms of action of the intervention to suggest refinements and combinatorial therapies to facilitate further recovery. Physiological and immunohistochemical approaches will be employed to identify reorganized descending and reflex pathways, effects on serotonin regulation of spinal excitability, and changes in the structure of spinal perineuronal nets that could promote synaptic plasticity.

描述（由申请人提供）：拟议项目的目标是开发一种神经假体装置，该装置使用有针对性的、活动依赖性的脊柱刺激来改善颈脊髓损伤（SCI）后手臂和手部的运动恢复。 该项目旨在通过使用脑机接口技术来利用神经可塑性的生理机制来推进临床实践。 运动缺陷严重影响患者的生活质量 SCI，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有效治疗多种神经系统疾病。 该临床前项目将评估电刺激在 SCI 大鼠模型中前肢运动缺陷康复中的新应用。 该策略旨在通过有针对性地刺激意志激活的神经回路来指导赫布可塑性，从而增强幸存的神经通路的功能。结果将为未来在患有 SCI 的人类受试者中使用脊髓刺激的临床试验奠定基础。 初步数据表明，由前肢肌肉活动触发的单通道脊柱内刺激可有效改善慢性 SCI 大鼠的运动表现。 具体目标 1 旨在通过探索使用皮层电图信号来触发刺激而不是肌肉活动以及对脊髓进行侵入性较小的表面刺激来优化单通道干预。 将部署新的电极技术用于皮质记录和表面刺激。 具体目标 2 将开发多通道刺激以扩展治疗能力。 具体目标 3 将确定如果在 SCI 亚急性期采用该疗法是否可以实现进一步康复。 具体目标 4 开始研究干预措施的作用机制，以提出改进和组合疗法以促进进一步康复。 将采用生理学和免疫组织化学方法来识别重组的下行和反射通路、对脊髓兴奋性的血清素调节的影响，以及可以促进突触可塑性的脊髓周围神经网络结构的变化。