Phase and amplitude EEG correlations change with disease progression in people with idiopathic rapid eye-movement sleep behavior disorder

Study objectives: Increased phase synchronization in electroencephalography (EEG) bands might reflect the activation of compensatory mechanisms of cognitive decline in people with neurodegenerative diseases. Here, we investigated whether altered large-scale couplings of brain oscillations could be linked to the balancing of cognitive decline in a longitudinal cohort of people with idiopathic rapid eye-movement sleep behavior disorder (iRBD). Methods: We analyzed 18 patients (17 males, 69.7±7.5 years) with iRBD undergoing high-density EEG (HD-EEG), presynaptic dopaminergic imaging, and clinical and neuropsychological assessments at two time points (time interval 24.2±5.9 months). We thus quantified the HD-EEG power distribution, orthogonalized amplitude correlation and weighted phase lag index at both time points and correlated them with clinical, neuropsychological and imaging data. Results: Four patients phenoconverted at follow-up (three cases of parkinsonism and one of dementia). At the group level, neuropsychological scores decreased over time, without reaching statistical significance. However, alpha phase synchronization increased and delta amplitude correlations decreased significantly at follow-up compared to baseline. Both large-scale network connectivity metrics were significantly correlated with neuropsychological scores but not with sleep quality indices or presynaptic dopaminergic imaging data. Conclusions: These results suggest that increased alpha phase synchronization and reduced delta amplitude correlation may be considered electrophysiological signs of an active compensatory mechanism of cognitive impairment in people with iRBD. Large-scale functional modifications may be helpful biomarkers in the characterization of prodromal stages of alpha-synucleinopathies.