Mechanisms of Motor Recovery after Subtotal Brain Injury

描述（由申请人提供）：中风是导致功能性残疾的主要原因，在美国每年有超过78万人受到影响。这种疾病对个人、社会和经济的负面影响是惊人的。在临床实践中，经常观察到运动皮层或其下行通路受损后会出现不同程度的运动恢复。尽管在成人大脑中似乎有相当大的功能可塑性，但对次全脑损伤后运动恢复的机制仍然知之甚少。在成年恒河猴中，我们的主要目标是验证一个假设，即手臂运动功能恢复的中心机制是通过位于同侧的完整扣带运动区皮质脊髓投影的重组发生的。在具有临床意义的时间间隔内，我们将通过研究孤立切除同侧手臂区域(a)初级运动皮层（M1）后，吻侧（M3）和尾侧（M4）扣带运动皮层的手臂区域皮质脊髓投影的神经可塑性适应来验证这一假设；b) M1和背外侧6区（LPMCd）；c) M1、LPMCd和辅助运动皮层（M2）。前两种病变类型模拟了最常见的中风形式，即大脑中动脉梗死。通过分析手在伸手过程中的三维轨迹，抓取和抬起过程中的力控制，以及使用2种专门的评估方法监测手的功能表现，仔细跟踪手的恢复。该项目将有助于更好地理解扣带运动皮层在同侧额叶运动皮层损伤后手臂运动恢复过程中的作用。这项工作还将评估位于大脑皮层病变同侧的完整运动区域的保留皮质脊髓投影的完整性是否为手部运动控制功能恢复的基础，以及在脑次全损伤后，完整皮质脊髓终端的长期重组是否伴随着平行皮质运动区域的补充。我们将确定激活扣带皮质脊髓系统自然（即非治疗性）募集的运动/运动前皮层损伤的类型，激活过程的时间以及这如何影响伸手和抓握过程。这一信息将有助于建立预测因素，以确定中风后可能有利发展的大量患者群体，因为扣带皮质脊髓投射的起源是由大脑前动脉（ACA）提供的，并且超过97%的首次缺血性中风患者没有出现ACA。此外，它将有助于指导创造性的康复干预方法，旨在加强前扣带参与恢复过程。

DESCRIPTION (provided by applicant): Stroke is the leading cause of functional disability affecting greater than 780,000 people a year in the United States. The negative personal, social and economic impacts of this disease are staggering. In clinical practice, it is a common observation that variable levels of motor recovery occur following damage of the motor cortex or its descending pathways. Although there appears to be considerable functional plasticity in the adult brain, the mechanisms underlying motor recovery following subtotal brain injury remain poorly understood. In adult rhesus monkeys, our major goal is to test the hypothesis that a central mechanism of functional recovery of arm movement occurs through reorganization of the corticospinal projection from intact cingulate motor areas located ipsilateral to a subtotal brain lesion. At clinically significant time intervals, we will test this hypothesis by studying neuroplastic adaptations of the corticospinal projection from the arm areas of the rostral (M3) and caudal (M4) cingulate motor cortices following isolated resection of the ipsilateral arm areas of a) the primary motor cortex (M1); b) M1 and dorsolateral area 6 (LPMCd) and; c) M1, LPMCd and the supplementary motor cortex (M2). The first two lesion categories model the most common form of stroke, namely middle cerebral artery infarction. Hand recovery will be carefully tracked by analyzing 3-D hand trajectory during reaching, force control during grasping and lifting, and monitoring functional hand performance using 2 specialized assessment methods. This project will lead to a greater understanding of the role of the cingulate motor cortices in the recovery process of arm movement following ipsilateral damage to the frontal motor cortices. This work will also assess whether the integrity of spared corticospinal projections from intact motor areas positioned ipsilateral to a lesion of the cerebral cortex underlie functional restitution of hand movement control and whether long-term reorganization of intact corticospinal terminals accompany the recruitment of parallel cortical motor areas after subtotal brain injury. We will determine the type of motor/premotor cortical lesion that activates natural (i.e., non-therapeutic) recruitment of the cingulate corticospinal system, the timing of the activation process and how this affects the reaching and grasping process. This information will assist in establishing predictors to identify a large patient population that may develop favorably after stroke since the origin of the cingulate corticospinal projection is supplied by the anterior cerebral artery (ACA) and the ACA is spared in greater than 97% of all first time ischemic stroke victims. Furthermore, it will assist in guiding creative rehabilitative intervention approaches aimed at enhancing anterior cingulate participation in the recovery process.