Neurophysiological Basis for Enhancing Motor Recovery After Stroke

增强中风后运动恢复的神经生理学基础

• 批准号: 10385691
• 负责人: Karunesh Ganguly
• 金额: --
• 依托单位: VETERANS AFFAIRS MED CTR SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-10-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10385691
• 关键词: Affect; Animals; Area; Behavior; Binding; Brain; Chronic; Complex; Corpus striatum structure; Data; Electrophysiology (science); Frequencies; Goals; Impairment; Individual; Knowledge; Learning; Lesion; Link; Medicine; Methods; Modeling; Motor; Motor Cortex; Movement; Nature; Neurologic; Outcome; Pattern; Performance; Play; Population Dynamics; Publishing; Recovery; Recovery of Function; Regulation; Rehabilitation therapy; Residual state; Rodent Model; Role; Site; Source; Stroke; Testing; Therapeutic; Training; United States; Upper Extremity; Veterans; Work; aging population; base; design; disability; experience; grasp; improved; kinematics; military veteran; motor impairment; motor recovery; motor rehabilitation; neural network; neurophysiology; neuroregulation; novel therapeutic intervention; novel therapeutics; post stroke; recruit; stroke model; stroke rehabilitation; stroke survivor

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.

中风是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 方法仍然存在实质性的长期残疾。重要的是，定量评估 已经发现，导致运动障碍的主要贡献者是碎片运动的存在 控制，其特征是子动物之间缺乏平滑而快速的过渡 多次尝试的不一致。此外，学习新运动还有一种辩护 序列。目前尚不清楚此类缺陷的精确电路基础是什么。 该提议的核心假设是任务依赖性招募受损 纹状体有助于零散的运动控制和学习不良。有一个很棒的 关注周围皮层（PLC）在恢复中的作用。但是，在完整的大脑中，皮质区域 与皮层区域的密切音乐会合作； M1与背外侧纹状体之间的相互作用 众所周知（DLS）在学习和产生平稳且一致的技能方面发挥着关键作用 动作。关于DLS在中风后如何促进运动恢复的情况知之甚少。我们的 初步数据表明，M1和DLS之间的协调与运动的“结合”直接相关 碎片可导致平稳且熟练的动作。我们进一步发现，DLS对于这种情况至关重要 执行; DLS的抑制增加了运动碎片。我们的数据还表明DLS 活动受到中风的影响，其活性随恢复而变化。 我们建议追求以下特定目的：1）确定与任务相关的振荡活动的作用 在DLS中，在皮质后的发起运动恢复期间控制运动碎片 中风; 2）确定在自发恢复过程中区域之间低频连贯性的作用 在涉及皮质和纹状体的中风的环境中； 3）确定配对刺激是否可以 增加协调性，从而改善运动结果。这些目标的完成将提供 设计专门针对皮质 - 纹状体活性的治疗方法的关键信息。 专注于这种动态神经元网络相互作用的靶向神经调节代表了一种新的 可以改变我们中风后上肢功能恢复能力的方向。