Double-blind, randomized, placebo-controlled clinical trial with gamma-band transcranial alternating current stimulation for the treatment of schizophrenic auditory hallucinations

Abstract

Abstract Gamma oscillations are essential for communication between brain regions, and 40Hz neural oscillation defects in schizophrenia. Due to the impaired functional connectivity of the left frontotemporal region, the information communication and integration between the frontal lobe and the temporo-parietal region of schizophrenia are faulty, thus produce auditory hallucinations. Homophasic transcranial alternating current stimulation is thought to enhance connectivity between different brain regions by modulating brain oscillations. In this work, we applied a frontal-temporal-parietal 40Hz-tACS stimulation strategy for treating auditory hallucinations and further explored the effect of tACS on functional connectivity of brain networks. 32 schizophrenia patients with refractory auditory hallucinations received 20 daily 20-min, 40Hz, 1-mA sessions of active or sham tACS on weekdays for 4 consecutive weeks, followed by a 2-week follow-up period without stimulation.Auditory hallucination symptom scores and 64-channel electroencephalograms were measured at baseline, week2, week4 and follow-up. For clinical symptom score, we observed a significant interaction between group and time for auditory hallucinations symptoms (F(3,90) = 26.964, p༜0.001), and subsequent analysis showed that the 40Hz-tACS group had a higher symptom reduction rate than the sham group at week4 (p = 0.036) and follow-up (p = 0.047). EEG results showed that, the 40Hz-tACS group had higher functional connectivity in the right and left frontal (F (1, 30) = 4.15, p = 0.051), right frontal to parietal (F (1, 30) = 7.24, p = 0.012), right frontal to occipital (F (1, 30) = 7.98, p = 0.008) and right intrafrontal (F (1, 30) = 4.13, p = 0.051) than the sham group at week4. Further, functional brain network controllability outcomes showed that the 40Hz-tACS group had increased average controllability (F (1, 30) = 6.26, p = 0.018) and decreased modality controllability (F (1, 30) = 6.50, p = 0.016) in the right frontal lobe compared to the sham group. Our study indicates that 40Hz-tACS may be an effective treatment for targeting symptoms specific to auditory hallucinations and altering functional connectivity and controllability at the network level.