NeuroImage · 2026
HD-tACS at 40 Hz improves consciousness and brain connectivity in prolonged disorders of consciousness: a randomized sham-controlled clinical trial.
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Hu Jun, Mou Chenye, Jiang Xiaoyi, Zhang Li, Ling Yi, Zhao Jiajia, Meng Fanxia, He Fangping, Wang Hanxiao, Peng Fujing, Ning Jing, Gao Jian, Xu Chuan, Xiao Jun, Zhao Sha, Yu Jie, Pan Gang, Luo Benyan
Аннотация
BACKGROUND: Frequency-specific high-definition transcranial alternating current stimulation (HD-tACS) may facilitate recovery in patients with prolonged disorders of consciousness (pDoC), but predictive biomarkers and mechanistic insights are limited.
OBJECTIVE: To investigate the therapeutic efficacy of 40 Hz or 4 Hz HD-tACS in pDoC.
METHODS: Sixty pDoC patients were randomized into four groups receiving 40 Hz or 4 Hz HD-tACS, each with a corresponding sham condition. Behavioral recovery was assessed via Coma Recovery Scale-Revised (CRS-R), network connectivity was analyzed with electroencephalography (EEG), and baseline 40 Hz auditory steady-state response (ASSR) was explored as a predictive biomarker.
RESULTS: Five days of 40 Hz HD-tACS yielded greater improvements of total CRS-R scores than 4 Hz or sham, particularly in visual and arousal subscales. EEG revealed strengthened short- and long-range connectivity quantified by phase-locking value (PLV), correlating with behavioral gains. At six months, 37.5% of 40 Hz patients got a good outcome with Glasgow Outcome Scale-Extended (GOS-E) score ≥ 4, which was significantly higher than that observed in the sham group (P = 0.019). Higher baseline ASSR predicted stronger network enhancement and clinical improvement.
CONCLUSIONS: 40 Hz HD-tACS promotes recovery and network reorganization in pDoC. Baseline ASSR may provide complementary information for understanding individual variability in responses to frequency-specific neuromodulation.
OBJECTIVE: To investigate the therapeutic efficacy of 40 Hz or 4 Hz HD-tACS in pDoC.
METHODS: Sixty pDoC patients were randomized into four groups receiving 40 Hz or 4 Hz HD-tACS, each with a corresponding sham condition. Behavioral recovery was assessed via Coma Recovery Scale-Revised (CRS-R), network connectivity was analyzed with electroencephalography (EEG), and baseline 40 Hz auditory steady-state response (ASSR) was explored as a predictive biomarker.
RESULTS: Five days of 40 Hz HD-tACS yielded greater improvements of total CRS-R scores than 4 Hz or sham, particularly in visual and arousal subscales. EEG revealed strengthened short- and long-range connectivity quantified by phase-locking value (PLV), correlating with behavioral gains. At six months, 37.5% of 40 Hz patients got a good outcome with Glasgow Outcome Scale-Extended (GOS-E) score ≥ 4, which was significantly higher than that observed in the sham group (P = 0.019). Higher baseline ASSR predicted stronger network enhancement and clinical improvement.
CONCLUSIONS: 40 Hz HD-tACS promotes recovery and network reorganization in pDoC. Baseline ASSR may provide complementary information for understanding individual variability in responses to frequency-specific neuromodulation.