Basal Ganglia Local Field Potentials as a Potential Biomarker for Sleep Disturbance in Parkinson's Disease

Abstract

Sleep disturbances, specifically decreases in total sleep time and sleep efficiency as well as increased sleep onset latency and wakefulness after sleep onset, are highly prevalent in patients with Parkinson's disease (PD). Impairment of sleep significantly and adversely impacts several comorbidities in this patient population, including cognition, mood, and quality of life. Sleep disturbances and other non-motor symptoms of PD have come to the fore as the effectiveness of advanced therapies such as deep brain stimulation (DBS) optimally manage the motor symptoms. Although some studies have suggested that DBS provides benefit for sleep disturbances in PD, the mechanisms by which this might occur, as well as the optimal stimulation parameters for treating sleep dysfunction, remain unknown. In patients treated with DBS, electrophysiologic recording from the stimulating electrode, in the form of local field potentials (LFPs), has led to the identification of several findings associated with both motor and non-motor symptoms including sleep. For example, beta frequency (13–30 Hz) oscillations are associated with worsened bradykinesia while awake and decrease during non-rapid eye movement sleep. LFP investigation of sleep has largely focused on the subthalamic nucleus (STN), though corresponding oscillatory activity has been found in the globus pallidus internus (GPi) and thalamus as well. LFPs are increasingly being recognized as a potential biomarker for sleep states in PD, which may allow for closed-loop optimization of DBS parameters to treat sleep disturbances in this population. In this review, we discuss the relationship between LFP oscillations in STN and the sleep architecture of PD patients, current trends in utilizing DBS to treat sleep disturbance, and future directions for research. In particular, we highlight the capability of novel technologies to capture and record LFP data in vivo, while patients continue therapeutic stimulation for motor symptoms. These technological advances may soon allow for real-time adaptive stimulation to treat sleep disturbances.