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，是功能性残疾的主要原因，在美国每年影响超过200万人。这些疾病对个人、社会和经济的负面影响令人震惊。在临床实践中，通常观察到不同水平的运动恢复，并在运动皮层或其下行通路受损后发生。虽然成年人的大脑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知之甚少。我们的主要目标是检验这一假设，即手臂运动功能恢复的中枢机制是通过重组位于同侧的额叶运动区的皮质脊髓投射到次全脑损伤，以及强迫使用疗法增强皮质脊髓连接。在临床显著的时间间隔和不同的强迫使用治疗持续时间下，我们将通过研究在单独切除同侧手臂区域后，辅助运动皮层（M2）手臂区域的皮质脊髓投射的神经可塑性适应来检验这一假设：a）初级运动皮层（M1）+背外侧运动前皮层（LPMCd）和; B）M1 + LPMCd +初级躯体感觉皮层（S1）。这两种病变类别都涉及运动皮层的一部分，这通常涉及人类中风的最常见形式，即大脑中动脉梗死。通过分析伸手和抓握过程中的三维手部和手指运动、抓握和提升过程中的力控制以及使用3种专门测试方法的双手协调来跟踪手部恢复。该项目将导致更好地理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。这项研究还将评估是否完整的备用皮质脊髓的预测从完整的运动区定位同侧的大脑皮层病变的基础功能恢复的手运动控制，以及是否长期重组完整的皮质脊髓终端伴随招聘平行皮质运动区次全脑损伤后。这些信息将有助于建立预测因素，以确定一个大的患者群体，可能会恢复良好的脑损伤后，适当的治疗。此外，它将有助于指导创造性的康复干预，旨在提高额叶皮层参与恢复过程。

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.