Consolidation of Motor Skills & Sleep Homeostasis in Parkinson's Disease

描述（由申请人提供）：在日常活动中使用行为惯例和运动技能，以实现高效和快速的表现。在帕金森病（PD）患者中，在疾病的早期阶段，自动例行程序的执行受到损害。这种损害逐渐变得更加严重，加剧了PD的运动症状并干扰了日常活动的执行。最近的研究表明，PD患者巩固运动技能记忆的能力可能会选择性受损。我们和其他实验室的新研究表明，运动技能的巩固非常依赖于睡眠。具体来说，在最近一项对健康受试者进行的高清脑电图（hd-EEG）研究中，我们发现学习一项视觉运动技能会在参与该任务的皮质区域（右顶叶）产生局部睡眠慢波活动（SWA）增加。最重要的是，SWA的增加与睡眠依赖的记忆巩固指数高度相关，SWA是反映睡眠需求积累的睡眠稳态的一个众所周知的标志。鉴于PD患者众所周知的睡眠问题，运动常规巩固与睡眠稳态之间的联系具有潜在的相关性。这一建议将验证PD患者运动技能巩固障碍与特定脑区睡眠稳态破坏有关的假设。具体而言，我们将确定PD患者是否：1)在运动学习任务的睡眠依赖性巩固方面存在缺陷；2)参与运动任务的脑区或其他脑区局部SWA稳态存在缺陷；3)经颅磁刺激（TMS）是否能增强SWA并恢复睡眠依赖性记忆巩固。我们将通过详细的运动学调查来测试这些假设，并首次使用整夜高清脑电图记录。为了避免混淆因素，我们将重点关注那些没有药物且其他方面健康的初始PD患者。研究结果将为PD患者SWA稳态的区域性缺陷提供第一个证据；它们还将表明这种缺陷是否与记忆巩固受损有机制联系，并可能通过经颅磁刺激恢复。与NINDS的目标一致，这些研究将为合理的治疗方法提供基础，以增强PD患者的睡眠稳态，提高他们的运动技能和生活质量。

DESCRIPTION (provided by applicant): Behavioral routines and motor skills are used in everyday activities for efficient and fast performance. In patients with Parkinson's disease (PD), the execution of automatic routines is impaired in the early stages of the disease. This impairment, which becomes progressively more severe, exacerbates the motor symptoms of PD and interferes with the execution of daily activities. Recent studies suggest that PD patients may be impaired selectively in their ability to consolidate motor skill memories. New work from our and other laboratories has shown that motor skill consolidation is exquisitely dependent on sleep. Specifically, in a recent study with high-definition electroencephalography (hd-EEG) in healthy subjects, we found that learning a visuomotor skill produced a local increase in sleep slow-wave activity (SWA) over a cortical area (right parietal) involved in the task. Most importantly, the increase in SWA, a well-known marker of sleep homeostasis that reflects the accumulation of sleep need, was highly correlated with sleep-dependent memory consolidation indices. The link between the consolidation of motor routines and sleep homeostasis is potentially relevant in view of the well-known sleep problems in PD patients. This proposal will test the hypothesis that the impairment in motor skill consolidation in PD patients is related to a disruption of sleep homeostasis in select brain regions. Specifically, we will determine whether PD patients: 1) have a defect in sleep-dependent consolidation of a motor learning task; 2) have a defect in local SWA homeostasis in the brain regions involved in the motor task or in other brain regions; 3) whether Transcranial Magnetic Stimulation (TMS) enhances SWA and restores sleep-dependent memory consolidation. We will test these hypotheses through detailed kinematic investigations and, for the first time, with whole-night hd-EEG recordings. To avoid confounding factors, we will focus on patients with initial PD who are drug-na'i've and otherwise healthy. The results will provide the first evidence concerning regional deficits in SWA homeostasis in PD patients; they will also indicate whether such deficits may be related mechanistically to impaired memory consolidation and may be restored by TMS. Consistent with the goals of NINDS, these studies will provide the basis for a rational therapeutic approach to enhancing sleep homeostasis in PD patients to improve their motor skills and quality of life.