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.
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