Enhanced delta-gamma phase-amplitude coupling during phasic rapid eye movement sleep in isolated rapid eye movement sleep behavior disorder

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.