The Impact of Deep Brain Stimulation of the Subthalamic Nucleus on Sleep–Wake Function and Circadian Rhythms in Patients with Parkinson's Disease

Abstract

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established therapy in advanced Parkinson's disease (PD) improving motor and non-motor signs including sleep. The mechanisms of sleep improvement are insufficiently understood. Objectives: The objective was to identify stimulation-dependent effects on the sleep–wake cycle and circadian clock regulation. Methods: Fourteen PD patients who underwent STN DBS (PD-DBS) were assessed before as well as 6 and 12 months post-surgery. As control groups, 18 PD patients under best medical treatment (PD-CON) and 25 healthy controls (H-CON) were also enrolled. Wrist actigraphy to measure sleep and sleep questionnaires, such as the PD Sleep Scale (PDSS), were applied and the expression of clock genes in peripheral blood was measured. Electrode placement in the STN was localized, and the local impact of STN DBS was estimated. Results: STN DBS improved daytime sleepiness 12 months post-surgery (P = 0.006) which was correlated with limbic VTA (r = 0.737, P = 0.006). PDSS scores decreased 6 months post-surgery (P = 0.050) and were positively associated with activation of the motor part of the STN (r = 0.582, P = 0.037). Time in bed increased after surgery and was also positively correlated with the activation of the motor part of the STN (r = 0.941, P = 0.005). There were no changes in clock gene expression between groups and over time (all P ≥ 0.323). Conclusions: Sleep and daytime sleepiness are improved after STN DBS in PD. Different STN sub-proportions contribute to these improvements. The changes in sleep appear not be driven by changes in clock gene expression.