From Neural Control of Movement to Treatments for Spinal Cord Injury

从运动的神经控制到脊髓损伤的治疗

• 批准号: 10631942
• 负责人: Monica A Perez
• 金额: $ 60.74万
• 依托单位: REHABILITATION INSTITUTE OF CHICAGO D/B/A SHIRLEY RYAN ABILITYLAB
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-17 至 2029-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10631942
• 关键词: Behavior; Behavioral; Caregiver Burden; Central Nervous System; Chronic; Chronic Phase; Development; Dimensions; Electromyography; Exercise; Funding; Goals; Healthcare; Human; Hyperreflexia; Individual; Injury; Knowledge; Light; Mediating; Methodology; Motor; Motor Neurons; Motor Pathways; Movement; Multiple Sclerosis; Muscle; Muscle Weakness; National Institute of Neurological Disorders and Stroke; Neurologic; Neuronal Plasticity; Pain; Pathway interactions; Persons; Physiological; Protocols documentation; Public Health; Recovery; Reflex action; Research; Residual state; Spasm; Spinal; Spinal Cord; Spinal cord injury; Stroke; Surface; Survival Rate; Symptoms; Synapses; System; Vertebral column; density; disability; experience; grasp; improved; motor behavior; nervous system disorder; neural; neuroimaging; neurophysiology; neuroregulation; randomized placebo-controlled clinical trial; rehabilitation strategy; spasticity; spinal cord imaging; success; tool; transmission process

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.

项目概要/摘要 在过去 15 年里，我们由 NINDS 资助的研究重点是了解下行传播 有或没有脊髓损伤的人类运动行为期间的运动通路和脊髓网络 （SCI），长期目标是最大化备用通路连接的活性以促进恢复 潜在的。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 与肌肉无力和功能相关行为不同，例如精细和粗略的抓握 与对照对象相比，进行了操作。这些下降运动系统的贡献不平衡 当存在痉挛和肌肉痉挛时发现，为反射亢进的机制提供了线索 继SCI。运动神经元对皮质脊髓、网状脊髓和传入输入的反应在任务中下降 依赖方式。我们的研究小组率先在 皮质脊髓通路，从赫布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改善运动 慢性不完全 SCI 后介导的恢复。 在本申请中，我们请求合并两项正在进行的 NINDS 资助的提案，重点关注控制 随意运动（R01NS090622）以及痉挛和肌肉痉挛（R01NS100810）。我们将利用我们的 现有知识产生新的研究，通过整合信息来挑战现有的范式 跨越 SCI 亚急性和慢性阶段的残余网络，并侧重于理解：a) 在一组广泛的幸存的下行运动通路和脊髓回路中传播，b）反射亢进 这些幸免的系统，以及 c) 基于神经可塑性的疗法。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、神经影像学和行为工具取得了成功。我们将雇用更多 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了解 人类与亚急性和慢性 SCI 之间的联系。成功完成这项研究将提高我们的 了解运动和症状（包括痉挛和肌肉痉挛）的神经控制 其他神经系统疾病（即中风、多发性硬化症和 ALS）。这项研究还可能提供新的 治疗和评估患有 SCI 和其他神经系统疾病的人类的途径。