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

巩固运动技能

• 批准号: 7565951
• 负责人: M. Felice Marina GHILARDI
• 金额: $ 35.02万
• 依托单位: CITY COLLEGE OF NEW YORK
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-15 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7565951
• 关键词: Address; Animals; Area; Attention; Behavioral; Bicycling; Brain region; Caregivers; Cerebrum; Characteristics; Collaborations; Computers; Data; Defect; Development; Disease; Disease Progression; Electroencephalography; Electrophysiology (science); Frequencies; Goals; Heart; Homeostasis; Human; Image; Impairment; Intervention; Investigation; Laboratories; Learning; Levodopa; Life; Link; Location; Long-Term Potentiation; Memory; Memory impairment; Motor; Motor Cortex; Motor Skills; Movement; National Institute of Neurological Disorders and Stroke; Neuronal Plasticity; Parietal; Parietal Lobe; Parkinson Disease; Patients; Performance; Pharmaceutical Preparations; Pharmacological Treatment; Process; Psychophysiology; Quality of life; REM Sleep; Research Personnel; Role; Rotation; Shoes; Sleep; Sleep Disorders; Slow-Wave Sleep; Staging; Symptoms; Synaptic plasticity; Testing; Therapeutic; Therapeutic Intervention; Time; Training; Transcranial magnetic stimulation; Universities; Wakefulness; Wisconsin; Work; Writing; base; effective therapy; experience; implicit memory; improved; indexing; kinematics; motor impairment; motor learning; neuromechanism; non rapid eye movement; novel; programs; response; skills; sleep regulation; visual motor

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.

描述（由申请人提供）：在日常活动中使用行为习惯和运动技能，以实现高效、快速的表现。帕金森病 (PD) 患者的自动程序执行能力在疾病早期就会受到损害。这种损伤逐渐变得更加严重，加剧了帕金森病的运动症状，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，运动技能的巩固很大程度上取决于睡眠。具体来说，在最近对健康受试者进行的高清脑电图（hd-EEG）研究中，我们发现学习视觉运动技能会导致参与任务的皮质区域（右顶叶）的睡眠慢波活动（SWA）局部增加。最重要的是，SWA（一种众所周知的睡眠稳态标志物，反映睡眠需求的积累）的增加与睡眠依赖性记忆巩固指数高度相关。鉴于帕金森病患者众所周知的睡眠问题，运动习惯的巩固和睡眠稳态之间的联系可能具有相关性。该提案将检验以下假设：PD 患者运动技能巩固受损与特定大脑区域睡眠稳态的破坏有关。具体来说，我们将确定帕金森病患者是否：1）在运动学习任务的睡眠依赖性巩固方面存在缺陷； 2) 参与运动任务的大脑区域或其他大脑区域的局部 SWA 稳态存在缺陷； 3）经颅磁刺激（TMS）是否增强SWA并恢复睡眠依赖性记忆巩固。我们将通过详细的运动学研究并首次通过整夜高清脑电图记录来测试这些假设。为了避免混淆因素，我们将重点关注未接受过药物治疗且其他方面健康的初始 PD 患者。该结果将提供有关 PD 患者 SWA 稳态局部缺陷的第一个证据；他们还将表明这种缺陷是否可能与受损的记忆巩固存在机械相关性，并且可以通过 TMS 来恢复。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，从而提高他们的运动技能和生活质量。