Mechanisms of Motor Recovery after subtotal Brain Injury

描述(申请人提供)：中风和创伤性脑损伤通常累及大脑皮层，是导致功能性残疾的主要原因，在美国每年总共有200多万人受到影响。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，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。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心机制是通过重组位于次全脑损伤同侧的完整额叶运动区的皮质脊髓投射而发生的，并且强迫使用疗法增强了皮质脊髓联系。在临床有意义的时间间隔和不同的强迫使用治疗持续时间下，我们将通过研究辅助运动皮质(M2)臂区皮质脊髓投射的神经再生适应来检验这一假说。切除同侧臂区：a)初级运动皮质(M1)+背外侧运动前皮质(LPMCd)和；b)M1+LPMCd+初级躯体感觉皮质(S1)。这两类病变都涉及运动皮质的一部分，而运动皮质通常是人类最常见的中风形式，即大脑中动脉梗塞。手部恢复将通过分析伸手和抓取过程中的三维手部和手指运动，抓取和抬起过程中的力控制，以及使用3种专门的测试方法进行双手协调来跟踪。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。这项研究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。这些信息将有助于建立预测指标，以确定脑损伤后通过适当治疗可能恢复良好的大量患者群体。此外，它还将协助指导创造性的康复干预措施，以加强额叶皮质对恢复进程的参与。

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.