Enhanced Delta-gamma Phase Amplitude Coupling during Phasic REM Sleep in isolated REM Sleep Behavior Disorder

Abstract Study Objectives This study aims to analyze phase-amplitude coupling (PAC) patterns during rapid eye movement (REM) sleep in patients with isolated REM sleep behavior disorder (iRBD), compared with demography-matched healthy control (HC) participants. Methods At baseline, electroencephalogram data from 13 iRBD patients and 10 HCs during REM sleep were analyzed. During follow-up, four patients (converters) later converted to alpha-synucleinopathies. Phasic and tonic REM states were determined by eye movement in 3 s epochs. PAC was compared between the groups, and correlations with clinical indicators were investigated. Additionally, the contribution of each electrode to PAC components was assessed. Results Patients with iRBD exhibited increased delta (1–3 Hz)-gamma (30–50 Hz) PAC only during the phasic REM state, but not during the tonic state, compared to the HCs (p < .05). Elevated PAC in patients negatively correlated with the REM atonia index (p = 0.011) and olfactory function (p = 0.038). Increase PACs were predominent in the fronto-temporo-occipital regions (corrected p < .05). Furthermore, patients showed reduced gamma-amplitude contributions of the parietal region (corrected p < .05). This reduction exhibited a progressively decreasing trend from HC to nonconverters, and further to converters (p for trend = 0.044). Conclusions Our findings suggest PAC patterns during REM sleep could provide pathophysiological insights for iRBD. The widespread increase of PAC and reduced gamma-amplitude contribution in the parietal region suggest PAC during phasic REM sleep as potential biomarkers for disease progression in iRBD.