Mechanisms of Motor Receovery after Subtotal Brain Injury

描述(由申请人提供)：在美国，中风是每年影响超过78万人的功能性残疾的主要原因。这种疾病对个人、社会和经济的负面影响令人震惊。在临床实践中，运动皮质或其下行通路受损后，常可观察到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。在成年恒河猴身上，我们的主要目标是验证这一假说，即手臂运动的功能恢复的中枢机制是通过重组位于次全脑损伤同侧的完整扣带运动区的皮质脊髓投射来实现的。在临床上有意义的时间间隔，我们将通过研究单独切除a)初级运动皮质(M1)、b)M1和背外侧6区(LPMCd)和c)M1、LPMCd和辅助运动皮质(M2)的同侧臂区(M3)和尾侧(M4)扣带回运动皮质的皮质脊髓投射的神经可塑性适应来检验这一假说。前两种病变类别模拟了最常见的中风形式，即大脑中动脉梗塞。通过分析伸手过程中的3-D手部轨迹，抓取和提举过程中的力量控制，以及使用2种专门的评估方法监测功能性手的性能，将仔细跟踪手的恢复。这个项目将有助于更好地理解扣带运动皮质在同侧额叶运动皮质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损伤同侧的完整运动区的剩余皮质脊髓投射的完整性是否构成手运动控制功能恢复的基础，以及在次全脑损伤后，完整皮质脊髓终末的长期重组是否伴随着平行皮质运动区的招募。我们将确定激活扣带皮质脊髓系统的自然(即，非治疗性)招募的运动/运动前皮质损伤的类型，激活过程的时间，以及这如何影响到达和抓住过程。这些信息将有助于建立预测指标，以确定卒中后可能发展良好的大量患者群体，因为扣带回皮质脊髓投射的起源是由大脑前动脉(ACA)供应的，而在所有首次缺血性卒中患者中，超过97%的人幸免于扣带皮质脊髓投射。此外，它将帮助指导创造性的康复干预方法，旨在加强前扣带回参与恢复过程。

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.