From Neural Control of Movement to Treatments for Spinal Cord Injury

项目摘要/摘要 在过去的15年里，我们由NINDS资助的研究一直专注于了解下行传播 有脊髓损伤和无脊髓损伤的人类运动行为中的运动通路和脊髓网络 (SCI)，长期目标是最大限度地发挥备用通路连接的活性，以促进恢复 潜力。我们的研究表明，在脊髓损伤患者中，皮质脊髓和网状脊髓系统起作用。 区别于肌肉无力和功能相关的行为，如细小和粗大的抓取 手法，与对照受试者相比。这些下行马达系统的不平衡贡献 在出现痉挛和肌肉痉挛时被发现，这为反射亢进的机制提供了线索 追随SCI。在一项任务中，运动神经元对皮质脊髓、网状脊髓和传入输入的反应性降低 依赖的态度。我们的研究小组率先使用了依赖于峰时的可塑性在 皮质脊髓通路：从Hebbian可塑性的基本原则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改善了运动- 慢性不完全性脊髓损伤后的介导性康复。 在此应用程序中，我们要求合并两个正在进行的由NINDS资助的提案，这两个提案的重点是控制 随意运动(R01NS090622)和痉挛和肌肉痉挛(R01NS100810)。我们将利用我们的 现有知识，以产生新的研究，通过整合信息挑战现有范式 跨SCI亚急性期和慢性期的残余网络，并侧重于了解：a) 在一套广泛的备用下行运动通路和脊髓回路中传递，b)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过去的基础上 使用尖端的神经生理学、神经成像和行为工具取得成功。我们将雇佣更多的员工 先进的脊髓成像方法、高密度表面肌电记录和新的 使用多维行为工具进行生理检查以增强我们对残留物的理解 亚急性和慢性脊髓损伤与人类的联系。成功完成这项研究将增加我们的 了解神经控制运动和症状，包括痉挛和肌肉痉挛，在 其他神经系统疾病(如中风、多发性硬化症和肌萎缩侧索硬化症)。这项研究也可能为我们提供新的 治疗和评估患有脊髓损伤和其他神经疾病的人类的途径。

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.