Sept 12, 2023

Pathological pallidal beta activity in Parkinson’s disease is sustained during sleep and associated with sleep disturbance

**Yin Z, Ma R, An Q, Xu Y, Gan Y, Zhu G, Jiang Y, Zhang N, Yang A,Meng F, Kühn AA, Bergman H, Neumann WJ* , Zhang J*.**

*equal contribution

Nat Commun. 2023; 14: 5434. Published online 2023 Sep 5.
doi: 10.1038/s41467-023-41128-6

Sleep disorders are common in people with Parkinson’s disease (PD) and have a significant impact on their quality of life. Insomnia and rapid eye movement (REM) sleep behaviour disorder are frequent manifestations of PD-related sleep disturbance that can be correlated with, and sometimes predict, other non-motor symptoms such as cognitive decline.

Unfortunately, current therapies, such as medications and continuous deep brain stimulation (DBS), do not specifically target sleep disturbances in PD. This gap highlights the need for personalised therapeutic approaches.

PD is associated with excessive beta activity in the basal ganglia, but the relationship between this activity and sleep disturbances remains unclear. While modulation of beta activity during sleep cycles has been reported, the pathophysiological impact of this activity pattern on sleep quality in human patients remains unknown. Recently, a potential relationship between beta activity and sleep disturbance has been reported for the first time in a non-human basic science model of Parkinson’s disease, urging further investigation in humans.

We aim to address this important knowledge gap by comparing pathological beta activity across sleep cycles in the internal pallidum of PD patients with a control group of subjects suffering from dystonia, another neurological disorder treated with internal pallidum DBS. To investigate the clinical potential of beta activity as a biomarker of sleep quality, we recorded pallidal local field potentials during polysomnography in these patient groups.

We found that PD patients had sustained and increased beta activity during wakefulness, REM and non-REM sleep, which correlated with sleep disturbance. Simulation of adaptive stimulation showed that sleep-related changes in beta activity are not accounted for by current algorithms, with potentially negative consequences for sleep quality and overall quality of life in patients.

Prof. Andrea Kühn

Prof. Dr. Andrea Kühn is the spokesperson of the TRR 295 ReTune and Head of Movement Disorders and Neuromodulation Unit at the Department of Neurology with Experimental Neurology at Charité – Universitätsmedizin Berlin.

Prof. Hagai Bergman

Prof. Hagai Bergmann is full Professor at the Edmond & Lily Safra Center for Brain Sciences, Hebrew University of Jerusalem.

He is Project Leader of Project C03 – Closed-loop neurostimulation in MPTP monkeys. In this project, the team will assemble a comprehensive database of the functional connectivity within and between nuclei of the basal ganglia of non-human primates throughout the sleep-wake cycle, before and following MPTP intoxication and development of Parkinson’s disease.

Prof. Wolf-Julian Neumann

Prof. Wolf-Julian Neumann is Assistant Professor for Interventional and Cognitive Neuromodulation at the Movement Disorder and Neuromodulation Unit at Charité – Universitätsmedizin Berlin. He is Project Leader of Project B03 which focuses on decoding therapy-related inhibition / disinhibition signaling through M1 ECoG and subthalamic LFP real-time classification in patients with Parkinson’s disease.