Shaping Motor Recovery After Stroke Using Activity-Dependent Stimulation

摘要/摘要 后天脑损伤是导致运动障碍和残疾的主要因素。当这些伤害发生时， 几乎没有被证实的促进行为恢复的策略。很明显，由以下因素造成的赤字 皮质损伤并不完全是梗死区丧失的结果。更确切地说，这是一场 向梗死区投射和从梗死区接收投射的备用区域的协调神经活动 对减值有显著影响。正是在这些备用区域内，显著的神经可塑性 发生。这是康复治疗的基础--运动学习和使用可以通过 驱动神经活动，表现为新的和加强的神经连接，可以补偿或 改善运动障碍。目前有促进这种神经活动的策略，例如 经颅磁刺激和经颅直流电刺激，但这些策略是非 具体，并且具有较低的时空分辨率。新的战略，以利用 神经可塑性对于塑造损伤后神经通讯的重建方式是必要的。一 其机制是依赖于活动的刺激，其中一个人的固有单一单位神经活动 区域通过皮质内微刺激驱动远处区域的活动。这创造了一种人造的 可能导致触发器和目标内部以及之间的生理变化的通信桥 地区。这项研究的目标是1)开发一种新的汽车驾驶后恢复方法 使用活动依赖刺激桥接皮质不连续区域造成的皮质损伤2) 了解脑皮质电刺激引起的神经可塑性相关的机制变化 创造新策略以促进与神经损伤相关的损伤后恢复的任期目标 沟通。中心假设是，在初级运动皮质损伤后，许多由此产生的运动 缺陷是由于失去了初级运动程序和体感信息的整合 运动皮质，重建运动前-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的连接 运动前皮质和体感皮质之间的活动(目标2)，这应该会导致表达的增加 驱动新的解剖连接所需的神经可塑性标记(目标3)。有了这些信息，它 将有可能设计出更有效地驱动神经再生机制的循证策略 对于缺血性损伤后运动损伤的恢复是必要的。

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.