Acoustic-electric trigeminal-nerve stimulation enhances functional connectivity in patients with disorders of consciousness

Aim: Disruption of functional brain connectivity is thought to underlie disorders of consciousness (DOC) and recovery of impaired connectivity is suggested as an indicator of consciousness restoration. We recently found that rhythmic acoustic-electric trigeminal-nerve stimulation (i.e., musical stimulation synchronized to electrical stimulation of the trigeminal nerve) in the gamma band can improve consciousness in patients with DOC. Here, we investigated whether these beneficial stimulation effects are mediated by alterations in functional connectivity. Methods: Sixty-three patients with DOC underwent 5 days of gamma, beta, or sham acoustic-electric trigeminal-nerve stimulation. Resting-state electroencephalography was measured before and after the stimulation and functional connectivity was assessed using phase-lag index (PLI). Results: We found that gamma stimulation induces an increase in gamma-band PLI. Further characterization revealed that the enhancing effect is (i) specific to the gamma band (as we observed no comparable change in beta-band PLI and no effect of beta-band acoustic-electric stimulation or sham stimulation), (ii) widely spread across the cortex, and (iii) accompanied by improvements in patients' auditory abilities. Conclusion: These findings show that gamma acoustic-electric trigeminal-nerve stimulation can improve resting-state functional connectivity in the gamma band, which in turn may be linked to auditory abilities and/or consciousness restoration in DOC patients.