EEG-defined differences in functional networks following beta-band transcranial alternating current stimulation in...

Severe disruption of cortico-thalamocortical circuits underlies disorders of consciousness (DOC). Beta-band (20 Hz) transcranial alternating current stimulation (tACS) can be used to probe frontal oscillatory synchrony, yet its potential to acutely modulate large-scale network dynamics in DOC is unknown.

We applied 20 Hz tACS (1 mA) for 30 min over the frontal cortex (F3 and F4, International 10-20 system) in 28 patients with DOC. Offline functional near-infrared spectroscopy (fNIRS) was used to quantify hemoglobin (HbO)-based functional connectivity (FC) and graph-theoretical network properties, including small-world properties (clustering coefficient, C_p; path length, L_p) and global efficiency (global efficiency, E_g; local efficiency, E_loc) at pre-stimulation resting-state measurement for 5 min (pre-stim), the first post-stimulation resting-state measurement for 5 min (post-stim1), and the second post-stimulation resting-state measurement for 5 min (post-stim2). Subgroups were defined by baseline video-electroencephalography (vEEG) pathology as moderately abnormal (n = 11) and diffuse slowing (n = 14); 3 patients excluded (incomplete vEEG).

Frontal 20 Hz tACS was associated with transient enhancement of FC across the measured cortical network at post-stim1 (pFDR < 0.05), selectively strengthening intra-and interhemispheric and intra-nodal connectivity before resolving by post-stim2. Crucially, the effects were pathology-dependent, and visual-motor integration pathways (right occipital lobe to left motor cortex; right primary somatosensory cortex to left occipital lobe) emerged exclusively in DOC patients with moderately abnormal background but not in those with diffuse slowing. Concurrent acute network reorganization at post-stim1 (all p < 0.05) featured increased C_p, E_g, and E_loc, along with decreased L_p, all normalizing by post-stim2. Clinically, Coma Recovery Scale-Revised scores correlated positively with average FC of HbO (pre-stim: r = 0.47; post-stim2: r = 0.41) and Area Under the Curve (AUC) of E_g (pre-stim: r = 0.44), and negatively with AUC of L_p (pre-stim: r = - 0.41; all p < 0.05).

Frontal beta-tACS was associated with state-dependent changes in functional network organization in DOC, with dynamic fNIRS measures that may be useful for tracking these changes. These findings provide preliminary descriptive evidence of short-term network changes associated with beta-tACS and may help guide future controlled studies of targeted neuromodulation in patients with DOC.