Abstract
<title>Abstract</title> <p>Disorders of consciousness (DoC), including unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), remain difficult to diagnose at the bedside. Electroencephalography (EEG) microstate analysis captures large-scale resting-state dynamics at high temporal resolution, but evidence on how neuromodulation reshapes these dynamics is limited. We evaluated the effect of a single 20-minute session of 40 Hz transcranial alternating current stimulation (tACS) over the bilateral dorsolateral prefrontal cortex (DLPFC) on resting-state EEG microstate parameters in DoC and their relationships with behavioral consciousness scores. In a prospective, single-arm, open-label design, thirty-one patients (21 male; mean age 46.9 ± 16.2 years; 19 MCS, 12 UWS) underwent resting-state EEG immediately before and after a 2 mA, 40 Hz bilateral DLPFC tACS session. Microstate maps A–G were back-fitted to individual recordings, and mean duration, occurrence, coverage, and global explained variance (GEV) were extracted. Pre/post comparisons used paired t-tests with Benjamini–Hochberg correction; correlations with the Coma Recovery Scale–Revised (CRS-R) and the Simplified Evaluation of CONsciousness Disorders (SECONDs) used Spearman rank correlations. After tACS, the mean duration of microstate A decreased significantly (71.6 to 65.8 ms; t(30) = -3.19, p = 0.003, adjusted p = 0.023). Baseline GEV correlated with CRS-R (rho = 0.49, p = 0.005), and post-stimulation microstate E occurrence and coverage were inversely associated with CRS-R, while group-level CRS-R and SECONDs scores were unchanged. A single 40 Hz DLPFC tACS session produced measurable changes in resting-state microstate architecture without immediate behavioral improvement, supporting microstate-guided individualized neuromodulation in DoC.</p>