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

描述（由申请人提供）：拟议项目的目的是开发一种神经假体器械，该器械使用靶向活动依赖性脊髓刺激来改善颈脊髓损伤（SCI）后手臂和手部运动恢复。 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 然而，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各种神经系统疾病。 这个临床前项目将评估电刺激在SCI大鼠模型中用于前肢运动缺陷康复的新应用。 该策略的目的是通过有针对性地刺激意志激活的神经回路，指导赫布可塑性，以增强备用神经通路的功能。结果将为未来的临床试验奠定基础，在人体脊髓刺激与SCI。 初步数据表明，单通道，脊髓内刺激触发的前肢肌肉的活动，以改善慢性SCI大鼠的运动表现的有效性。 具体目标1旨在通过探索使用皮质电图信号来触发刺激而不是肌肉活动，以及脊髓的侵入性较小的表面刺激来优化单通道干预。 将部署一种新的电极技术用于皮层记录和表面刺激。 Specific Aim 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的亚急性期引入治疗，是否可以产生进一步的恢复。 具体目标4开始调查干预的作用机制，以提出改进和组合疗法，以促进进一步恢复。 生理学和免疫组织化学方法将用于识别重组的下行和反射通路，对脊髓兴奋性的5-羟色胺调节的影响，以及可能促进突触可塑性的脊髓神经元束膜网结构的变化。

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.