Shaping Motor Recovery After Stroke Using Activity-Dependent Stimulation

使用活动依赖性刺激塑造中风后运动恢复

• 批准号: 9789677
• 负责人: DAVID GUGGENMOS
• 金额: $ 15.3万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-20 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9789677
• 关键词: Address; Affect; Anatomy; Animals; Area; Automobile Driving; Behavioral; Brain; Brain Injuries; Brain region; Communication; Computer software; Custom; Distant; Driving neuroplasticity; Electroencephalography; Etiology; Functional Magnetic Resonance Imaging; Global Change; Goals; Growth Associated Protein 43; Human; Impairment; Implant; Individual; Injury; Ischemia; Knowledge; Lead; Left; Lesion; Link; Measures; Methods; Microelectrodes; Monitor; Motor; Motor Activity; Motor Cortex; Neocortex; Neuronal Plasticity; Outcome; Pathway interactions; Pattern; Performance; Physiological; Process; Rattus; Recovery; Recovery of Function; Rehabilitation therapy; Research; Role; Sensory; Shapes; Signal Transduction; Site-Directed Mutagenesis; Somatosensory Cortex; Spinal Cord; Stroke; Synaptophysin; Techniques; Testing; Therapeutic; Training; Transcranial magnetic stimulation; United States; awake; base; cohort; design; disability; evidence base; growth differentiation factor 10; hemiparesis; improved; in vivo; insight; ischemic lesion; microstimulation; motor deficit; motor disorder; motor function improvement; motor function recovery; motor impairment; motor learning; motor recovery; neurophysiology; novel; novel strategies; post stroke; programs; rehabilitation strategy; relating to nervous system; repaired; response; somatosensory; temporal measurement

Summary/Abstract Acquired brain injuries are major contributors to motor impairment and disability. When these injuries occur, there are few proven strategies for promoting behavioral recovery. It is clear that the deficits resulting from cortical injury are not entirely the result of the loss of the infarcted area. Rather, the disruption in the coordinated neural activity of spared regions projecting to and receiving projections from the infarcted area significantly contribute to the impairment. It is within these spared regions that significant neuroplasticity occurs. This is the basis of rehabilitative therapies – motor learning and usage can promote reorganization by driving neural activity that manifests in new and strengthened neural connections that can compensate for or improve the motor impairment. There are current strategies to promote this neural activity, such as transcranial magnetic stimulation and transcranial direct current stimulation, but these strategies are non- specific, and have low spatial and temporal resolution. New strategies to utilize the intrinsic mechanisms of neuroplasticity for shaping how neural communication is reestablished after an injury are necessary. One mechanism for this is activity-dependent stimulation, where the intrinsic single-unit neural activity of one region drives the activity in a distant region through intracortical microstimulation. This creates an artificial communication bridge that may lead to physiological changes within and between the trigger and target regions. The objectives of this research are 1) to develop a novel approach for driving recovery after motor cortical injury by bridging disconnected regions of cortex using activity-dependent stimulation and 2) to understand neuroplasticity-related mechanistic changes resulting from the cortical stimulation with the long- term goals of creating novel strategies to promote recovery after injury related to disruption in neural communication. The central hypothesis is that, after primary motor cortical injury, many of the resulting motor deficits are due to the loss of integration of motor programs and somatosensory information within primary motor cortex, and that reestablishing premotor-sensory communication will result in behavioral improvements (Aim 1). In addition, this artificial bridging will lead to strengthened connections of the task-related neural activity between premotor and somatosensory cortex (Aim 2) which should result in the increased expression of neuroplastic markers necessary for driving novel anatomical connections (Aim 3). With this information, it will be possible to design evidence-based strategies that more effectively drive the neuroplastic mechanisms that are necessary for recovery of motor impairments after ischemic injury.

摘要/摘要 获得的脑损伤是运动障碍和残疾的主要因素。当这些伤害发生时， 促进行为恢复的策略很少。显然，定义由 皮质损伤并不完全是梗塞区域丧失的结果。相反，中断 豁免区域的协调神经活动投射到并接收来自梗塞区域的项目 正是在这些幸免的区域内，重要的神经成形术 发生。这是康复疗法的基础 - 运动学习和使用可以通过 驱动神经元活动，表现出可以补偿或加强神经元连接的 当前有促进这种神经活动的策略，例如 跨界磁刺激和trancranial直流电流刺激，但这些策略是非 - 具体，并且具有低空间和临时分辨率。利用固有机制的新策略 需要在受伤后重新建立神经元通信的神经可塑性。一 这是活性依赖性刺激的机制，其中一个固有的单单元神经活性 区域通过皮质内微刺激在遥远区域中驱动活性。这创建了人造 通信桥可能会导致触发器和目标之间的物理变化 地区。这项研究的目标是1）开发一种新颖的方法来推动运动后恢复的方法 通过使用活动依赖性刺激桥接皮层区域的皮质损伤，2） 了解与长期的皮质刺激导致神经可塑性相关的机械变化 创建新型策略以促进与神经中断相关的受伤后恢复的术语目标 沟通。中心假设是，在原发性运动皮质损伤之后，许多由此产生的电动机 缺陷是由于电动机计划和主要感知信息的整合损失所致 运动皮层以及重建前运动感觉的连接将导致行为改善 （目标1）。此外，这种人造桥接将导致与任务相关的神经的连接加强 前运动皮层和体感皮质之间的活性（AIM 2），这应该导致表达增加 推动新型解剖连接所需的神经塑性标记（AIM 3）。有了这些信息， 可以设计基于证据的策略，以更有效地推动神经塑性机制 缺血性损伤后恢复运动障碍所必需的。