EEG-defined differences in functional networks following beta-band transcranial alternating current stimulation in patients with disorders of consciousness: a pilot study

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.