A Neurophysiological Approach to Post-Stroke Motor Recovery

中风后运动恢复的神经生理学方法

• 批准号: 10660831
• 负责人: Tanuj Gulati
• 金额: $ 41.75万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10660831
• 关键词: Acute; Back; Brain; Brain Injuries; Brain region; Cerebellar Cortex; Cerebellum; Chronic; Clinical; Contralateral; Coupled; Data; Devices; Electric Stimulation; Electricity; Electrophysiology (science); Etiology; Event; Hand; Hippocampus; Knowledge; Learning; Learning Skill; Link; Memory; Monitor; Motor; Motor Cortex; Motor Skills; Movement; Neocortex; Neurologic Symptoms; Neurons; Outcome; Patients; Pattern; Performance; Persons; Process; Rattus; Recovery; Recovery Support; Rehabilitation therapy; Research; Rodent; Role; Sleep; Sleep Stages; Slow-Wave Sleep; Stroke; Structure; System; Task Performances; Testing; Thalamic structure; Time; United States; Work; awake; disability; efficacy testing; grasp; hand rehabilitation; improved; injured; learning strategy; memory consolidation; motor learning; motor recovery; motor skill learning; neocortical; neural; neurological rehabilitation; neurophysiology; non rapid eye movement; novel; novel strategies; optogenetics; post stroke; rehabilitation strategy; skills; sleep spindle; stroke model; stroke recovery

Project Summary Stroke is a leading cause of disability in the United States. While there have been advancements in neurorehabilitation strategies, many patients continue to suffer from chronic disability, underscoring the need for further research into novel approaches to rehabilitation. Sleep remains relatively understudied in stroke studies even though there is evidence that lack of sleep following a stroke worsens neurological symptoms and long-term outcomes. Thus, sleep may be a useful target in developing new rehabilitation strategies. We propose to study the cortical and cerebellar regions during sleep to elucidate the systems-level neural processing that is linked to performance gains during the recovery period. Our recent work has shown that non-rapid eye movement (NREM) sleep processing in the motor cortex (M1) of healthy rats is linked to performance improvements in a motor task. Additionally, it is widely acknowledged that motor learning of clinically important and continuous movements has cerebellar correlates. Interestingly, recent work has shown that NREM sleep spindles have a cerebellar origin. Sleep spindles are widely known to be involved in reactivating awake learning activity, but these studies have more commonly focused on the neocortex, hippocampus, and thalamus. However, the extent to which NREM spindle oscillations in the cerebellum covary with the spindle oscillations in the neocortical regions (and if they reactivate awake single neuronal activity in both regions) during sleep to improve performance remains incompletely understood. Moreover, it is key to understand the sleep stages and accompanying neurophysiology that support post-stroke motor recovery in these structures, as well as the extent to which they can be modulated to enhance recovery. In this proposal, we take a systems-level approach to: (i) understand the coordinated NREM sleep processes in cortico-cerebellar networks that are associated with motor learning/ recovery in intact and stroke-injured rats, specifically if spindle activity is temporally locked in these regions; (ii) establish necessity of NREM sleep- related neural processing in skill consolidation and recovery through optogenetics; and (iii) test if augmentation of these sleep-related neural events using electrical stimulation of cerebellum enhances recovery. We will use simultaneous large-scale electrophysiologic monitoring of cortico-cerebellar networks with electrical stimulation and optogenetics in a rodent stroke model to test the following hypothesis: coupled NREM sleep activity in the intact and ipsilesional spared M1 and contralateral cerebellar cortex underlies motor learning or recovery after stroke, learning is reduced when this synchronization is disrupted via optogenetic inhibition of the cerebellar activity, and learning is increased when this synchronization is boosted via electrical stimulation of the cerebellum.

项目摘要 中风是美国残疾的主要原因。虽然在这方面取得了进展， 神经康复策略，许多患者继续遭受慢性残疾，强调需要 以进一步研究康复的新方法。睡眠在中风中的研究相对不足 尽管有证据表明中风后睡眠不足会导致神经系统症状， 长期成果。因此，睡眠可能是开发新的康复策略的有用目标。我们 我建议在睡眠中研究皮层和小脑区域，以阐明系统水平的神经 与恢复期间的性能增益相关的处理。我们最近的工作表明， 健康大鼠运动皮层（M1）中的非快速眼动（NREM）睡眠过程与以下因素有关： 在运动任务中的表现改善。此外，人们普遍认为， 临床上重要的连续运动与小脑相关。有趣的是，最近的研究表明， NREM睡眠纺锤波起源于小脑众所周知，睡眠纺锤波与 重新激活清醒时的学习活动，但这些研究通常集中在新皮层， 海马体和丘脑。然而，小脑中NREM纺锤波振荡的程度 与新皮层区域中的纺锤波振荡协变（并且如果它们重新激活清醒的单个神经元 活动）以提高表现仍然不完全清楚。而且是 了解睡眠阶段和支持中风后运动的伴随神经生理学的关键 这些结构的恢复，以及在何种程度上可以调整，以提高恢复。在这 建议，我们采取系统级的方法：（i）了解协调的NREM睡眠过程， 与完整和中风损伤大鼠的运动学习/恢复相关的皮质-小脑网络， 特别是如果纺锤体活动暂时锁定在这些区域;（ii）建立NREM睡眠的必要性- 通过光遗传学在技能巩固和恢复中的相关神经处理;以及（iii）测试是否增强 这些睡眠相关的神经活动，使用小脑的电刺激增强恢复。我们将使用 皮质-小脑网络电刺激同步大规模电生理监测 和光遗传学来测试以下假设： 完整的和同病灶的备用M1和对侧小脑皮质是运动学习或恢复的基础， 中风时，当这种同步通过小脑的光遗传学抑制而被破坏时，学习能力就会降低。 当这种同步通过电刺激大脑皮层时， 小脑