Neurophysiological Basis for Enhancing Motor Recovery After Stroke

中风是导致退伍军人残疾的主要原因。尽管中风康复方面取得了重大进展 方法继续存在大量的长期残疾。重要的是，量化评估 他们发现运动障碍的一个主要原因是运动的碎片化 控制，其特征是子运动和子运动之间缺乏平稳和快速的过渡 多次尝试不一致。此外，在学习新动作方面也存在缺陷 序列。目前尚不清楚造成这种赤字的确切电路基础是什么。 这一建议的中心假设是，任务依赖型招聘受损的 纹状体导致运动控制支离破碎和学习不良。已经有了一个很棒的 重点关注损伤周围皮质(PLC)在康复中的作用。然而，在完好的大脑中，皮质区域 与皮质下区域密切配合工作；M1与背外侧纹状体之间的相互作用 众所周知，学习(DLS)在学习和培养流畅和一致的技能方面发挥着关键作用 动静。关于DLS如何促进中风后的运动恢复，人们知之甚少。我们的 初步数据显示，M1和DLS之间的协调直接与运动的“绑定”有关 碎片可以产生流畅、快速、熟练的动作。我们进一步发现，DLS对于这样的 执行；抑制DLS增加了运动的碎片化。我们的数据还表明，DLS 活动受到中风的影响，其活动随着康复而变化。 我们建议追求以下具体目标：1)确定与任务相关的振荡活动的作用 DLS在调节皮质后自发运动恢复过程中运动碎裂中的作用 卒中；2)确定区域之间的低频连贯性在自然恢复中的作用 在中风同时涉及皮质和纹状体的情况下；3)确定配对刺激是否可以 增强协调性，从而改善运动效果。完成这些目标将提供 设计专门针对皮质-纹状体活动的治疗方法的关键信息。 关注这种动态神经网络相互作用的靶向神经调节代表了一种新的 可以改变我们促进中风后上肢功能恢复的能力的方向。

Stroke is a major cause of disability in veterans. Despite significant advances in stroke rehabilitation methods there continue to be substantial long-term disability. Importantly, quantitative assessments have found that a major contributor to motor impairments is the presence of fragmented movement control, characterized by a lack of smooth and fast transitions between sub-movements and inconsistency over multiple attempts. Furthermore, there is a deficit in learning new movement sequences. It remains unclear what is the precise circuit basis for such deficits. The central hypothesis of this proposal is that impaired task-dependent recruitment of the striatum contributes to fragmented movement control and poor learning. There has been a great focus on the role of perilesional cortex (PLC) in recovery. In the intact brain, however, cortical areas work in close concert with subcortical regions; interactions between M1 and the dorsolateral striatum (DLS) are known to play a critical role in learning and generating smooth and consistent skilled movements. Little is known about how the DLS might contribute to motor recovery after stroke. Our preliminary data shows that coordination between M1 and DLS is directly linked to “binding” of movement fragments to result in a smooth and fast skilled action. We further found that DLS is essential for such execution; inhibition of DLS increased movement fragmentation. Our data also demonstrates that DLS activity is affected by stroke and that its activity changes with recovery. We propose to pursue the following specific aims: 1) Determine the role of task-related oscillatory activity in the DLS in regulating movement fragmentation during spontaneous motor recovery after cortical stroke; 2) Determine the role of low-frequency coherence between areas during spontaneous recovery in the setting of a stroke that involves both cortex and striatum; 3) Determine if paired stimulation can increase coordination and thereby improve motor outcomes. Completion of these aims will provide critical information for designing therapeutic approaches that specifically target cortico-striatal activity. Focusing on targeted neuromodulation of such dynamic neural network interactions represents a new direction that could transform our ability to augment recovery of upper extremity function following stroke.