Cortical–Subthalamic Interplay During Eyes-Open and Eyes-Closed Resting States in Parkinson’s Disease Patients

Resting-state eye conditions modulate cortical oscillations, but their impact on subthalamic nucleus (STN) and cortico-STN dynamics in Parkinson's disease (PD) remains poorly understood. Here, we characterized electrophysiological changes in the STN and cortical interactions during eyes-open (EO) and eyes-closed (EC) conditions in 12 PD patients undergoing deep brain stimulation surgery. Spontaneous local field potentials in the STN (STN-LFP) and surface electroencephalogram (EEG) activity were simultaneously obtained on postoperative days 2-3 in the OFF-medication state. Power spectral density (PSD), coherence (COH), and Granger causality measures between STN-LFPs and frontal-occipital cortical areas were analyzed. These metrics revealed significant EO-EC differences, particularly in the low-frequency (LF, 4-12[Formula: see text]Hz) range. Although LF power increased across all regions during EC relative to EO, only STN and frontal EEG showed statistically significant changes. EC elicited increased frontal-STN COH within both the LF and low-beta bands (13-21[Formula: see text]Hz), accompanied by enhanced occipital-STN coupling in the low-beta range. In contrast, the influence of the alpha-band frontal cortex on the STN was more pronounced during EO. These findings confirm that eye states may differentially modulate functional connectivity through widespread cortical and STN-cortical interactions and suggest that, in unmedicated PD, EC and EO dynamically modulate large-scale cortical-STN network activity.