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。尽管中风康复取得了重大进展 方法继续存在实质性的长期残疾。重要的是，定量评估 我发现运动障碍的一个主要原因是运动的碎片化 控制，其特征在于子运动之间缺乏平滑和快速的过渡， 多次尝试的不一致性。此外，在学习新动作方面存在缺陷 序列的目前还不清楚这种缺陷的确切电路基础是什么。 这项建议的中心假设是，受损的任务依赖性招聘的 纹状体有助于分散的运动控制和学习能力差。有了很大 关注病灶周围皮质（PLC）在恢复中的作用。然而，在完整的大脑中， 与皮层下区域密切合作; M1和背外侧纹状体之间的相互作用 (DLS)众所周知，在学习和培养顺利、一致的技能方面发挥着关键作用 动作关于DLS如何有助于中风后运动恢复，我们知之甚少。我们 初步数据表明，M1和DLS之间的协调与运动的“结合”直接相关 片段，以导致一个顺利和快速熟练的行动。我们进一步发现，DLS是必不可少的， 执行;抑制DLS增加运动碎片。我们的数据还表明，DLS 活动受到中风的影响，其活动随着恢复而变化。 我们提出了以下具体目标：1）确定任务相关振荡活动的作用 在DLS中调节皮质后自发运动恢复期间的运动碎片 中风; 2）确定自发恢复期间区域之间低频相干性的作用 在涉及皮层和纹状体的中风的情况下; 3）确定配对刺激是否可以 增加协调性，从而改善运动结果。这些目标的实现将为 设计治疗方法的关键信息，专门针对皮质-纹状体活动。 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 这可能会改变我们的能力，以增加恢复中风后上肢功能的方向。