Shaping Motor Recovery After Stroke Using Activity-Dependent Stimulation

总结/摘要 获得性脑损伤是导致运动障碍和残疾的主要原因。当这些伤害发生时， 很少有被证实的促进行为恢复的策略。很明显，由于 皮质损伤不完全是梗塞区域丧失的结果。相反， 投射到梗死区域和接收来自梗死区域的投射的备用区域的协调神经活动 这对减值有很大的影响。正是在这些备用区域中， 发生。这是康复治疗的基础-运动学习和使用可以促进重组， 驱动神经活动，表现在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- 特异性，并且具有低的空间和时间分辨率。新的战略，利用内在机制， 神经可塑性对于塑造损伤后如何重建神经通信是必要的。一 这种机制是活动依赖性刺激，其中一个人的内在单单位神经活动 区域通过皮质内微刺激驱动远处区域的活动。这就创造了一个人造的 可能导致触发器和目标内部和之间的生理变化的通信桥梁 地区本研究的目的是：1）开发一种新的方法来恢复运动后的驾驶能力 通过使用活动依赖性刺激桥接断开的皮质区域造成的皮质损伤，以及2） 了解神经可塑性相关的机制变化所造成的皮质刺激与长- 长期目标是创造新的策略，以促进与神经系统破坏有关的损伤后的恢复。 通信中心假设是，在原发性运动皮层损伤后，许多由此产生的运动神经元可能会被激活。 缺陷是由于运动程序和躯体感觉信息的整合损失， 运动皮层，并且重新建立运动前感觉沟通将导致行为改善 (Aim 1）。此外，这种人工桥接将导致与任务相关的神经元之间的连接得到加强。 运动前区和躯体感觉皮层（Aim 2）之间的活动，这应导致表达增加 驱动新的解剖连接所必需的神经可塑性标记物（目标3）。有了这些信息， 将有可能设计基于证据的策略，更有效地推动神经可塑性机制， 是缺血性损伤后运动损伤恢复所必需的。

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.