Plasticity in the Spinal Cord to Enhance Motor Retraining after Stroke

每年大约有6000名退伍军人管理局因中风入院。目前的功能恢复率 中风后与运动相关的缺陷在很大程度上是不令人满意的。经济负担继续增加 限制康复的时间，强调需要采取新的战略，增加 康复计划的效果和效率。涉及皮质的神经调节策略 刺激已经被作为辅助治疗来研究，以提高康复效果 卒中。已经提出，以其他神经结构为靶点可能提供新的途径来增强 康复的效果。 拟议研究的总体目标是加强皮质脊髓对偏瘫患者的传递。 靶向脊髓皮质神经突触的退伍军人手部固有肌肉 绳索基于尖峰时序的可塑性原理。满足有两个主要目标 这个目标：1)检查功能和结构神经生理机制潜在的 对这种神经调节策略的反应，以及2)探索皮质-丘脑-神经元突触可塑性 卒中后可在运动再训练中增强自主运动输出和推动进步。 将对突触前和突触后动作电位进行计时，使其到达皮质-突触神经细胞 基于传导时间的特定序列和特定时间窗口内的突触 从单个响应延迟计算得出。在目标1中，重复突触前和突触后的动作 将提供电位，并将测量各种神经生理反应以评估 皮质脊髓传递的变化。在目标2中，将使用三重刺激技术来测量 中心传导故障和扩散谱成像分数各向异性将用于 评估皮质脊髓脊髓束的完整性。将使用这些功能和结构特征 目的：评价以脊髓突触为靶点的神经调节的反应。目标3实验 将测试皮质脊髓传递的变化如何改变对自愿运动输出的控制 视觉运动任务绩效。在研究塑性机制的前三个目标的基础上， AIM 4将试点一种机制驱动的干预措施，以促进运动再培训期间的进步。 研究团队由神经生理学、神经工程、 神经成像和中风神经康复，因此，处于有利地位，以满足建议的 项目目标。这一职业发展奖也将帮助厄宾博士成为一名独立的 退伍军人事务部的调查员。厄尔宾博士致力于临床研究事业。 目标是开发一条促进恢复功能独立的调查路线 残疾退伍军人。作为该奖项的一部分，培训经验将 让乌尔宾博士获得神经成像和高级神经刺激技术方面的新技能。 由指导小组监督的职业发展计划中的其他活动将提供 他需要接受必要的培训才能获得独立地位。总体而言，这个奖项将帮助乌尔宾博士 在退伍军人管理局科学界内制定公认的研究计划的途径。

Approximately 6000 VA admissions for stroke occur each year. Current rates of functional recovery from movement-related deficits after stroke are largely unsatisfying. Economic burdens continue to place limits on the length of rehabilitation, emphasizing a need for new strategies that increase the efficacy and efficiency of rehabilitation programs. Neuromodulatory strategies involving cortical stimulation have been examined as adjunctive therapies to enhance rehabilitation outcomes after stroke. It has been proposed that targeting other neural structures may offer new avenues to enhance the effects of rehabilitation. The broad objective of the proposed research is to strengthen corticospinal transmission to hemiparetic intrinsic hand muscles in veterans with stroke by targeting corticomotoneuronal synapses in the spinal cord based on principles of spike timing-dependent plasticity. There are two major goals for satisfying this objective: 1) examine functional and structural neurophysiological mechanisms underlying the response to this neuromodulatory strategy, and 2) explore how corticomotoneuronal synaptic plasticity after stroke can enhance voluntary motor output and drive progression during motor retraining. Presynaptic and postsynaptic action potentials will be timed to arrive at the corticomotoneuronal synapse in a particular sequence and within a specific temporal window based on conduction times calculated from individual response latencies. In Aim 1, repeated pre- and postsynaptic action potentials will be delivered and various neurophysiological responses will be measured to evaluate changes in corticospinal transmission. In Aim 2, the triple stimulation technique will be used to measure failures in central conduction, and diffusion spectrum imaging fractional anisotropy will be used to estimate corticospinal spinal tract integrity. These functional and structural characteristics will be used to evaluate the response to neuromodulation targeting synapses in the spinal cord. Aim 3 experiments will test how the change in corticospinal transmission alters the control of voluntary motor output during visuomotor task performance. Building on the first three aims investigating mechanisms of plasticity, Aim 4 will pilot a mechanism-driven intervention to enhance progression during motor retraining. The research team is comprised of experts in the areas of neurophysiology, neural engineering, neuroimaging, and stroke neurorehabilitation and, therefore, is well positioned to satisfy the proposed project goals. This Career Development Award will also help establish Dr. Urbin as an independent investigator within the VA RR&D service. Dr. Urbin is committed to pursuing a clinical research career with the objective of developing a line of inquiry that promotes restored functional independence for veterans living with disability. The training experiences that will take place as part of this award will allow Dr. Urbin to acquire new skills in neuroimaging and advanced neurostimulation techniques. Additional activities in the career development plan overseen by the mentorship team will provide the necessary training for him to achieve independent status. Overall, this award will help Dr. Urbin along the path to developing a recognized research program within the VA scientific community.