Resting-state cortical alpha frequency in Parkinson’s disease and multiple system atrophy: associations with diagnosis, age, and symptom burden

Abstract

Parkinson’s disease (PD) and multiple system atrophy (MSA) are clinically overlapping neurodegenerative disorders that present with a complex, heterogeneous burden of motor and non-motor symptoms. Resting-state EEG reveals that cortical alpha slowing is a hallmark of pathological aging, yet its specific presence and clinical significance in these distinct synucleinopathies remain incompletely understood. Therefore, precisely quantifying the individual alpha frequency serves as a critical, non-invasive approach to characterize cortical network dysfunction across synucleinopathies and evaluate how aging moderates its association with clinical symptom burden. We analyzed source-reconstructed resting-state EEG data from 104 participants, comprising patients with PD, patients with the parkinsonian (MSA-P) and cerebellar subtypes (MSA-C) of MSA, and healthy controls. To accurately capture oscillatory dynamics, a data-driven masking empirical mode decomposition approach was applied to extract the individual alpha frequency across canonical cortical networks. General linear models tested diagnostic group differences, age-related effects, and age-dependent associations between individual alpha frequency and clinical symptom scores. Relative to healthy controls, both PD and MSA-C exhibited significant lower cortical IAF, whereas MSA-P showed no significant global IAF difference. At the network level, significant reduction of IAF was detected in the visual and dorsal attention networks in both PD and MSA-C. Advancing age independently contributed to alpha slowing across all participants without accelerating the disease-related trajectories. Notably, chronological age significantly moderated the relationship between alpha slowing and non-motor symptoms. In older patients, reduced individual alpha frequency was strongly associated with a higher burden of overall non-motor, autonomic, and psychiatric/cognitive symptoms, a relationship not observed in younger patients or with motor symptom severity. Cortical alpha slowing was detected in PD and MSA-C, but not in MSA-P. Age independently contributes to alpha slowing and strengthens its association with non-motor symptom burden, supporting age-aware interpretation of resting-state electroencephalography biomarkers in synucleinopathies.