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 获得性脑损伤是导致运动障碍和残疾的主要原因。 几乎没有经过验证的促进行为恢复的策略。 皮质损伤并不完全是梗塞区域丧失的结果，而是梗塞区域破坏的结果。 投射到梗塞区域并接收来自梗塞区域的投射的幸存区域的神经协调活动 正是在这些幸存区域内，显着的神经可塑性导致了损伤。 这是康复治疗的基础——运动学习和使用可以通过以下方式促进重组。 驱动神经活动，表现为新的和强化的神经连接，可以补偿或 目前有一些策略可以促进这种神经活动，例如 经颅磁刺激和经颅直流电刺激，但这些策略都是非 特定的，并且具有低空间和时间分辨率利用内在机制的新策略。 神经可塑性对于塑造受伤后如何重建神经通讯是必要的。 其机制是活动依赖性刺激，其中一个固有的单单元神经活动 区域通过皮质内微刺激驱动远处区域的活动，这创造了一种人工。 沟通桥梁，可能导致触发器和目标内部以及之间的生理变化 本研究的目标是 1) 开发一种电机后驾驶恢复的新方法。 通过使用活动依赖性刺激桥接断开的皮质区域来损伤皮质；2) 神经可塑性相关的机制变化是由于了解长期的皮质刺激而产生的 制定新策略以促进与神经破坏相关的损伤后恢复的长期目标 中心假设是，在原发性运动皮质损伤后，许多由此产生的运动损伤。 缺陷是由于初级阶段运动程序和体感信息的整合缺失造成的 运动皮层，重建前运动感觉沟通将导致行为改善 （目标 1）此外，这种人工桥接将加强与任务相关的神经元的连接。 前运动皮层和体感皮层之间的活动（目标 2）应导致表达增加 驱动新的解剖连接所必需的神经可塑性标记（目标 3）。 将有可能设计基于证据的策略，更有效地驱动神经可塑性机制 这是缺血性损伤后运动障碍恢复所必需的。