Adaptive Neurostimulation to Restore Sleep in Parkinson's Disease (Aim 2)

Overview

Parkinson's Disease (PD) is the second most common of the age-related neurodegenerative disorders, affecting over 1,900 adults per 100,000 over the age of 80 in the US. The prevalence of sleep dysfunction in PD is estimated at nearly 80-90% which includes sleep fragmentation, insomnia, rapid eye movement (REM or dream sleep) Sleep Behavior Disorder (RBD), Restless legs syndrome (RLS), periodic limb movement, excessive daytime sleepiness, and sleep apnea. Sleep is vital to homeostasis, cognition, and nervous system repair. The dysfunctional sleep accompanying PD adversely affects both motor and non-motor symptoms, resulting in diminished quality of life for both patients and caregivers, including impairments in mood and behavior, and increased morbidity and mortality. Knowledge of sleep phenomenology and pathology in humans has largely been informed by analysis of non-invasive scalp electroencephalogram (EEG), and despite the profound importance of sleep, the underlying neural circuits important for controlling sleep and wakefulness in humans remain poorly understood. This study assesses whether adaptive stimulation of the Subthalamic Nucleus (STN) drives changes in sleep episode maintenance and improves sleep quality. Participants are adults with PD who experience inadequate motor symptom relief, and who have been offered implantation of a deep brain stimulator system targeting STN for the treatment of motor symptoms (standard-of-care). Prior to surgery, participant sleep patterns will be assessed with questionnaires and monitored with a non-invasive watch-like device. Approximately four months after implantation surgery, participants will each receive 2 1-week deep brain stimulation (DBS) treatments and 1 1-week control session with no DBS in random order. Sleep patterns will again be monitored during the treatments and compared to the patterns before surgery.

IIn previous studies, investigators examined the use of local field potentials (LFP) recorded from Subthalamic Nucleus (STN) - Deep brain stimulation (DBS) electrodes to identify unique spectral patterns in STN oscillatory activity that correlate with distinct sleep cycles. This offered insight into sleep dysregulation and supported the idea that biomarkers from STN-recorded LFP could be used to identify specific sleep stages. Data from this study directly informed the development and optimization of an adaptive stimulation algorithm. The current study will assess the efficacy of the adaptive stimulation algorithm and will test the working hypothesis that modulation of STN during nighttime sleep will normalize sleep behavior by offsetting aberrant signaling in the sleep network. Investigators will use subjective assessments, 3-week actigraphy, and nocturnal polysomnogram (PSG), in 20 Parkinson's Disease (PD) participants for 3-weeks prior to surgery and again 4-months after DBS implantation during the interventions. The time between surgery and the start of interventions allows DBS and medication to be therapeutically optimized for PD motor symptoms. Investigators will compare chronic open-loop stimulation to adaptive stimulation, and to a no-stimulation control group. All participants will experience each of the 3 interventions in random order and be blinded to the type of intervention received. The study hopes to validate a therapeutic intervention for the burdensome non-motor symptom of sleep dysfunction in PD, and to fill a critical gap in our understanding of the contribution of STN-DBS to ameliorating sleep-wake disturbances in PD. The acquisition of these data will improve the understanding of the role of basal ganglia, specifically STN, in sleep homeostasis in PD. It is expected that STN-DBS will improve sleep-wake parameters in both the PSG and actigraphy recordings but that adaptive stimulation, targeted at sleep-stage biomarkers, will further optimize sleep and alleviate this non-motor burden in PD. Specifically, investigators predict that adaptive more so than chronic open-loop STN-DBS during sleep will decrease non-consolidated sleep, reduce the frequency of awakenings, increase the percentage time spent in REM sleep, reduce daytime sleepiness, and increase subjective experience of restfulness and sleep quality.