Mechanisms of Motor Recovery after subtotal Brain Injury

描述（由申请人提供）：中风和创伤性脑损伤通常涉及大脑皮层，是导致功能残疾的主要原因，每年在美国影响超过200万人。这些疾病对个人、社会和经济的负面影响是惊人的。在临床实践中，通常观察到不同程度的运动恢复，并发生在运动皮层或其下行通路损伤之后。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。我们的主要目的是验证以下假设，即手臂运动功能恢复的主要机制是通过位于脑次全损伤同侧的完整额叶运动区皮质脊髓投影的重组发生的，以及强迫使用治疗增强皮质脊髓联系。在具有临床意义的时间间隔和不同的强制使用治疗持续时间下，我们将通过研究孤立切除同侧手臂区域的辅助运动皮质（M2）的皮质脊髓投影的神经可塑性适应来验证这一假设：a)初级运动皮质(M1) +背外侧运动前皮质（LPMCd）；b) M1 + LPMCd +初级体感觉皮层（S1）。这两种损伤类型都涉及到运动皮层的一部分，这部分通常与人类中风最常见的形式有关，即大脑中动脉梗死。通过3种专门的测试方法，分析手和手指在伸手和抓握过程中的三维运动、抓握和抬起过程中的力控制以及双手协调，来跟踪手部恢复。该项目将有助于更好地了解额叶运动皮质在皮质损伤后手臂运动恢复过程中的作用，并将确定短期和长期强迫使用治疗对恢复结果及其伴随的神经可塑性反应的影响。本研究还将评估位于大脑皮层病变同侧的完整运动区保留的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，完整皮质脊髓末梢的长期重组是否伴随着平行皮质运动区的补充。这一信息将有助于建立预测因素，以确定一个大的患者群体，他们可能在脑损伤后通过适当的治疗恢复良好。此外，它将有助于指导旨在加强额叶皮质参与恢复过程的创造性康复干预措施。

DESCRIPTION (provided by applicant): Stroke and traumatic brain injury often involve the cerebral cortex and are leading causes of functional disability collectively affecting greater than 2 million people per year in the United States. The negative personal, social and economic impacts of these disorders are staggering. In clinical practice, variable levels of motor recovery are commonly observed and 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. 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 frontal motor areas located ipsilateral to a subtotal brain lesion and that forced use therapy enhances the corticospinal linkage. At clinically significant time intervals and under different durations of forced use therapy, we will test this hypothesis by studying neuroplastic adaptations of the corticospinal projection from the arm area of the supplementary motor cortex (M2) following isolated resection of the ipsilateral arm areas of: a) the primary motor cortex (M1) + the dorsolateral premotor cortex (LPMCd) and; b) M1 + LPMCd + the primary somatosensory cortex (S1). Both of these lesion categories involve part of the motor cortex that is typically involved in the most common form of human stroke, namely middle cerebral artery infarction. Hand recovery will be tracked by analyzing 3-D hand and digit motion during reaching and grasping, force control during grasping and lifting, and bimanual coordination using 3 specialized testing methods. This project will lead to a greater understanding of the role of the frontal motor cortices in the recovery process of arm movement following cortical injury and will determine the effect that short and long-term forced use therapy has on recovery outcome and its accompanying neuroplastic response. This research 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. This information will assist in establishing predictors to identify a large patient population that may recover favorably after brain injury with appropriate therapy. Furthermore, it will assist in guiding creative rehabilitative interventions aimed at enhancing frontal cortical participation in the recovery process.