HD-tACS at 40 Hz improves consciousness and brain connectivity in prolonged disorders of consciousness: a randomized sham-controlled clinical trial.

In 30 seconds

This randomized, sham-controlled clinical trial evaluated 40 Hz and 4 Hz high-definition transcranial alternating current stimulation (HD-tACS) in 60 patients with prolonged disorders of consciousness. After five days, the 40 Hz group had greater improvement in Coma Recovery Scale-Revised scores than the 4 Hz and sham groups, particularly in visual and arousal domains. At six months, 37.5% of patients receiving 40 Hz stimulation had a Glasgow Outcome Scale-Extended score of at least 4, significantly more than in the sham group (P = 0.019). EEG connectivity gains correlated with behavioral improvement, and baseline auditory steady-state response predicted stronger responses.

Key findings

• Five days of 40 Hz HD-tACS improved total CRS-R scores more than 4 Hz stimulation or sham, particularly on visual and arousal subscales.
• At six months, 37.5% of patients in the 40 Hz group had GOS-E scores ≥ 4, significantly more than in the sham group (P = 0.019).
• EEG short- and long-range connectivity strengthened with 40 Hz stimulation, and connectivity changes correlated with behavioral gains.
• Higher baseline 40 Hz auditory steady-state response predicted greater network enhancement and clinical improvement.

Why it matters

The findings suggest that stimulation frequency may matter when investigating neuromodulation for prolonged disorders of consciousness, with 40 Hz stimulation associated with behavioral and connectivity improvements. The six-month outcome signal and potential predictive value of baseline auditory response may inform further research into treatment response, although the results do not establish routine clinical effectiveness.

What to keep in mind

The abstract does not report group sizes or detailed effect estimates for CRS-R changes, limiting assessment of the magnitude and precision of the reported benefits.