Neurophysiological Basis for Enhancing Motor Recovery after Stroke

 描述(由申请人提供)： 中风是导致退伍军人残疾的主要原因。尽管中风康复方法取得了重大进展，但仍有大量长期残疾。需要进行更多的研究，以开发新的方法来促进恢复。我们建议描述和调节在恢复过程中似乎发生的神经生理离线处理和性能增加(即，在实际训练停止后发生的系统级神经处理和性能增强)。基于我们的初步数据，我们将重点研究睡眠过程中离线处理的作用。更具体地说，使用多尺度电生理技术在多个分辨率下监控任务相关活动，我们建议进行研究，既描述睡眠如何增强中风后的运动恢复，又测试如何在康复期间最好地安排/修改睡眠。我们的基本假设是，睡眠中的“离线神经处理”有助于运动恢复。这一建议的主要目的是：(1)描述训练后促进运动恢复的睡眠阶段，(2)阐明在睡眠中促进运动学习的神经过程，以及(3)测试是否可以使用睡眠依赖加工的优化来促进恢复。利用大鼠长期的多尺度电生理记录，我们的初步数据表明，总体上睡眠，特别是非快速眼动(NREM)睡眠，在巩固非损伤和受损运动系统的运动技能方面发挥着重要作用。此外， 我们发现，在特定任务训练过程中形成的神经模式的“重放”与离线成绩的提高之间存在密切联系。这一建议的具体潜在假设是，在NREM睡眠期间神经元的离线“重放”对于中风后运动恢复的睡眠依赖的长期改善很重要。我们提出以下目标：(1)确定最佳睡眠时间和类型，以诱导中风后运动能力的短期脱机收益；(2)确定运动康复后中风周围皮质NREM睡眠依赖脱机加工的电生理相关性；(3)确定睡眠依赖加工是否可以积极促进长期运动恢复。我们提出的研究有可能发现有关运动恢复的网络和神经生理学基础的重要知识，并可以为神经调节促进中风后运动恢复提供新的方法。

 DESCRIPTION (provided by applicant): Stroke is a major cause of disability in veterans. Despite significant advances in stroke rehabilitation methods there continue to be substantial long-term disability. Additional research is required to develop new methods to facilitate recovery. We propose to delineate and modulate the neurophysiological offline processing and performance gains that appear to occur during the process of recovery (i.e. systems level neural processing and enhancements of performance that occur after the actual training has stopped). Based on our preliminary data, we will focus on the role of offline processing during sleep. More specifically, using multiscale electrophysiological techniques that monitor task-related activity at multiple resolutions, we propose to conduct studies that will both delineate how sleep enhances motor recovery after stroke as well as test how best to structure/modify sleep during rehabilitation. Our underlying hypothesis is that `offline neural processing' during sleep facilitates motor recovery. The main goals of this proposal are to: (1) delineate the stages of sleep that can promote motor recovery after training, (2) elucidate the neural processes that promote motor learning during sleep, and (3) test if optimization of sleep-dependent processing can be used to enhance recovery. Using long-term multi- scale electrophysiological recordings in rats, our preliminary data illustrates tht sleep in general, and non-rapid eye movement (NREM) sleep in specific, plays an important role in the consolidation of motor skills in both the non-injured and the injured motor system. Further, we found a close link between `replay' of neural patterns formed during task-specific training and offline gains in performance. The specific underlying hypothesis of this proposal is that offline `replay' of neurons during NREM sleep is important for sleep-dependent long-term improvements in motor recovery after stroke. We propose the following aims: (1) Determine the optimal amount and type of sleep to induce short-term offline gains in motor performance after stroke; (2) Determine the electrophysiological correlates of NREM sleep- dependent offline processing in the stroke perilesional cortex after motor rehabilitation; (3) Determine if sleep-dependent processing can be used to actively enhance long-term motor recovery. Our proposed research has the possibility of discovering important knowledge about the network and the neurophysiological basis of motor recovery and can offer novel approaches for neuromodulation to enhance motor recovery after stroke.