Behavioral and electrophysiological effects of network-based frontoparietal tDCS in patients with severe brain injury: A randomized controlled trial

Background: Transcranial direct current stimulation (tDCS) may promote the recovery of severely brain-injured patients with disorders of consciousness (DOC). Prior tDCS studies targeted single brain regions rather than brain networks critical for consciousness recovery. Objective: Investigate the behavioral and electrophysiological effects of multifocal tDCS applied over the frontoparietal external awareness network in patients with chronic acquired DOC. Methods: Forty-six patients were included in this randomized double-blind sham-controlled crossover trial (median [interquartile range]: 46 [35 – 59] years old; 12 [5 – 47] months post injury; 17 unresponsive wakefulness syndrome, 23 minimally conscious state (MCS) and 6 emerged from the MCS). Multifocal tDCS was applied for 20 min using 4 anodes and 4 cathodes with 1 mA per electrode. Coma Recovery Scale-Revised (CRS-R) assessment and 10 min of resting state electroencephalogram (EEG) recordings were acquired before and after the active and sham sessions. Results: At the group level, there was no tDCS behavioral treatment effect. However, following active tDCS, the EEG complexity significantly increased in low frequency bands (1–8 Hz). CRS-R total score improvement was associated with decreased baseline complexity in those bands. At the individual level, after active tDCS, new behaviors consistent with conscious awareness emerged in 5 patients. Conversely, 3 patients lost behaviors consistent with conscious awareness. Conclusion: The behavioral effect of multifocal frontoparietal tDCS varies across patients with DOC. Electrophysiological changes were observed in low frequency bands but not translated into behavioral changes at the group level.