Efficacy of Cortical Stimulation in a Non-Human Primate Model of Cortical Ischemi

中风是成年人运动功能障碍的主要原因。中风后的运动恢复与大脑皮层的功能和结构可塑性有关，但通常是不完整的，以长期残留缺陷为特征。与U54提案(翻译研究合作计划)中的其他几个研究团队合作，将在非人类灵长类动物皮质缺血模型中开发和优化一种新的治疗方法，以增强神经可塑性和运动恢复。这种治疗方法被称为皮质刺激(CS)，在康复训练过程中使用对未受梗塞损害的皮质区域进行低水平电刺激。在本提案(完整提案的项目3)中，将涉及三个具体目标。在目标1中，将在灵长类动物身上评估使用在U54啮齿动物项目中优化的CS参数来验证治疗的有效性和效果的持久性。在目标2中，要应用的最佳皮质位置 将对刺激进行评估。治疗将比较对梗塞周围初级运动皮质的刺激和对梗塞同侧完整的腹侧运动前皮质的刺激的效果。在目标3中，将评估在慢性脑梗塞后状态下开始治疗的疗效，并将其与在亚急性状态下开始治疗的疗效进行比较。刺激的位置将由目标2的结果决定。综合起来，这三个目标将为促进非人类灵长类动物中风导致的运动缺陷的行为恢复提供更好的理解。与U54提案相关的临床研究团队合作，希望从这种动物身上获得的洞察力 在临床试验期间，这种模式可以转化为人类患者治疗方法的改进。

Stroke is a leading cause of motor dysfunction in the adult population. Motor recovery from stroke is associated with functional and structural plasticity in the cerebral cortex, but is often incomplete and characterized by long-term residual deficits. In collaboration with several other investigative teams included in this U54 proposal (Cooperative Program in Translation Research), a new therapeutic approach to enhancing neuroplasticity and motor recovery will be developed and optimized in a nonhuman primate model of cortical ischemia. This therapy approach, termed Cortical Stimulation (CS), utilizes low-level electrical stimulation over cortical regions undamaged by the infarct, applied during rehabilitative training procedures. In this proposal (Project 3 of the full proposal), three specific aims will be addressed. In Aim 1, the verification of the efficacy of treatment and the persistence of effect using CS parameters optimized in U54 rodent projects will be evaluated in primates. In Aim 2, the optimal cortical location over which to apply stimulation will be evaluated. Therapy will compare the efficacy of stimulation over peri-infarct primary motor cortex with stimulation over the intact ventral premotor cortex ipsilateral to the infarct. In Aim 3, the efficacy of therapy initiated in the chronic post-infarct condition will be evaluated and compared to the efficacy of therapy initiated in the subacute condition. Location of stimulation will be determined by the results of Aim 2. Taken together, these three aims will provide a better understanding of the optimal parameters for promoting behavioral recovery from stroke-induced motor deficits in nonhuman primates. In collaboration with clinical investigative teams associated with this U54 proposal, it is hoped that the insights acquired from this animal model can be translated into improvements in treatment methods for human patients during clinical trials.