Abstract
Patients with idiopathic/isolated REM sleep behavior disorder (iRBD) are in the prodromal stage of alpha-synucleinopathies. Neurodegeneration early affects subcortical structures, including the substantia nigra, in iRBD patients. However, it remains unclear whether there is also an early neurodegeneration process affecting the cerebral cortex. We investigated whether EEG-derived metrics for aberrant cortical dynamics and imbalanced excitation-inhibition (E/I) correlate with disease severity in iRBD patients, aiming to better understand the pathophysiology progression from the prodromal to the overt stage of alpha-synucleinopathies. We retrospectively analyzed resting-state EEG recordings, as a marker of cortical function, and presynaptic dopaminergic imaging, a marker of subcortical function from 59 iRBD patients (9 female) who underwent longitudinal clinical evaluation alongside 46 age-matched healthy controls (22 female). We assessed power-law scaling in long-range temporal correlations (LRTCs), neuronal bistability, and functional E/I balance from the resting-state sensor EEG data and then correlated these to large-scale synchrony, nigrostriatal dopaminergic function, and clinical data. Compared with the control group, patients showed higher LRTCs and bistability in 2-7 Hz oscillations. Patients who developed parkinsonism/dementia exhibited hyperexcitability in 5-7 Hz compared with those who did not. This was also correlated with stronger phase synchrony. Both hyperexcitability in 5-7 Hz and bistability in 2-4 Hz negatively associated with nigrostriatal dopaminergic impairment. The iRBD patients, especially those closer to phenoconversion to parkinsonism or dementia, show clear aberrant cortical dynamics and hyperexcitability alongside substantia nigra impairment, suggesting that neurodegeneration in the prodromal stages affects both subcortical structures and cortical dynamics.