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

项目摘要 拟议项目的目标是继续开发实验室的 使用有针对性的、依赖活动的脊髓刺激来改善手臂的神经假体疗法 颈髓损伤(SCI)后手运动功能恢复。这项工程旨在推进 脑机接口技术在临床应用中的应用 神经可塑性的机制。 运动障碍严重影响脊髓损伤患者的生活质量，但目前的治疗方法 在运动能力上产生有限的改善。最新的临床和实验证据 提示电刺激神经系统是一种有效的治疗 各种神经性疾病。在这里，我们将扩展对电学的一种新应用的研究 对颈椎脊髓损伤模型大鼠前肢运动障碍的康复刺激。战略 旨在通过引导Hebbian可塑性来增强备用神经通路的功能 通过有针对性地刺激自愿激活的神经回路。结果将为 为未来在人类受试者中使用脊柱刺激的临床试验奠定基础。 以前的数据证明了多渠道椎管内刺激的有效性 由前肢肌肉活动触发以改善慢性脊髓损伤大鼠的运动能力。 具体目标1试图完成对刺激和刺激之间相互作用的描述 身体康复，以确立综合治疗的原则。具体目标2 将研究女性和男性在康复方面存在显著差异的可能原因 给予大鼠闭合环刺激。具体目标3将决定是否依赖于活动 硬膜外刺激，一种侵入性小得多且更容易转化为临床实践的方法 与椎管内刺激相比，在促进康复方面同样有效。

Project Summary The objective of the proposed project is to continue the laboratory’s development of 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. Here we will extend study of a novel application of electrical stimulation for rehabilitation of forelimb motor deficits in a rat model of cervical 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. Previous data demonstrated the effectiveness of multi-channel, intraspinal stimulation triggered by activity of forelimb muscles to improve motor performance in rats with chronic SCI. Specific Aim 1 seeks to complete the characterization of the interplay between stimulation and physical rehabilitation in order to establish principles for combining the therapies. Specific Aim 2 will examine possible causes underlying dramatic differences in recovery in female and male rats treated with the closed-loop stimulation. Specific Aim 3 will determine if activity-dependent epidural stimulation, a much less invasive and easier to translate to clinical practice approach than intraspinal stimulation, is as effective in facilitating recovery.