From Neural Control of Movement to Treatments for Spinal Cord Injury

项目概要/摘要 在过去的15年里，我们的NINDS资助的研究集中在了解下行传播 有和无脊髓损伤的人在运动行为期间的运动通路和脊髓网络 (SCI)，其长期目标是最大限度地提高备用通路连接的活性，以促进恢复 潜力我们的研究表明，在SCI患者中，皮质脊髓和网状脊髓系统有助于 差异肌肉无力和功能相关的行为，如精细和粗抓 操作，与对照组相比。这些下行运动系统的不平衡贡献 在痉挛和肌肉痉挛时发现，为反射亢进的机制提供了光 SCI之后。运动神经元对皮质脊髓、网状脊髓和传入输入的反应性在一项任务中降低， 依赖的方式。我们的研究小组率先使用尖峰时间依赖的可塑性， 皮质脊髓通路，从Hebbian可塑性的基本原理验证研究到随机安慰剂 对照临床试验表明皮质脊髓-运动神经元突触的可塑性可以改善运动- 慢性不完全SCI后的恢复。 在这个应用程序中，我们要求合并两个正在进行的NINDS资助的建议，重点是控制 随意运动（R 01 NS 090622）和痉挛状态和肌肉痉挛（R 01 NS 100810）。我们将利用我们 现有的知识产生新的研究，通过整合信息挑战现有的范式 在SCI的亚急性和慢性阶段的残留网络，并侧重于了解：a） B）在广泛分布的备用下行运动通路和脊髓回路中的反射亢进， 这些备用系统，以及c）基于神经可塑性的治疗。我们的研究方案将建立在我们的过去 使用尖端的神经生理学、神经影像学和行为工具取得成功。我们会雇用更多的人 先进的脊髓成像方法，高密度表面肌电图记录，以及新的 使用多维行为工具进行生理检查，以增强我们对残留的 人类与亚急性和慢性SCI的联系。这项研究的成功完成将增加我们的 了解运动和症状的神经控制，包括痉挛和肌肉痉挛， 其它神经障碍（即，中风、多发性硬化和ALS）。这项研究也可能提供新的 治疗和评估患有SCI和其他神经系统疾病的人的途径。

Project Summary/Abstract Over the last 15 years, our NINDS-funded research has focused on understanding transmission in descending motor pathways and spinal cord networks during motor behaviors in humans with and without spinal cord injury (SCI), with the long-term goal of maximizing the activity of spared pathway connections to enhance recovery potential. Our studies revealed that in people with SCI, corticospinal and reticulospinal systems contribute differentially to muscle weakness and functionally relevant behaviors, such as fine and gross grasping manipulations, compared with control subjects. Imbalanced contributions from these descending motor systems were found when spasticity and muscle spasms were present, providing light for the mechanisms of hyperreflexia following SCI. Motoneuron responsiveness to corticospinal, reticulospinal, and afferent input decreased in a task- dependent manner. Our research group pioneered the use of spike-timing dependent plasticity in the corticospinal pathway, from basic proof-of-principle studies on Hebbian plasticity to randomized placebo controlled clinical trials showing that plasticity at corticospinal-motoneuronal synapses improves exercise- mediated recovery after chronic incomplete SCI. In this application, we request to consolidate two ongoing NINDS-funded proposals that focus on the control of voluntary movement (R01NS090622) and spasticity and muscle spasms (R01NS100810). We will leverage our existing knowledge to produce new research that challenges the existing paradigm by integrating information across residual networks in the subacute and chronic phases of SCI and focuses on understanding: a) transmission in a widespread set of spared descending motor pathways and spinal circuits, b) hyperreflexia in these spared systems, and c) neuroplasticity-based therapies. Our research protocol will build on our past successes using cutting-edge neurophysiological, neuroimaging, and behavioral tools. We will employ more advanced spinal cord imaging methodologies, high-density surface electromyography recordings, and new physiological examinations using multidimensional behavioral tools to enhance our understanding of residual connections in humans with subacute and chronic SCI. Successful completion of this research will increase our understanding of the neural control of movement and symptoms, including spasticity and muscle spasms, in other neurological disorders (i.e., stroke, multiple sclerosis, and ALS). This research also may provide new avenues for treatments and assessment of humans with SCI and other neurological disorders.