High-Frequency Transcranial Random Noise Stimulation over the Left Prefrontal Cortex Increases Resting-State EEG Frontal Alpha Asymmetry in Patients with Schizophrenia

Reduced left-lateralized electroencephalographic (EEG) frontal alpha asymmetry (FAA), a biomarker for the imbalance of interhemispheric frontal activity and motivational disturbances, represents a neuropathological attribute of negative symptoms of schizophrenia. Unidirectional high-frequency transcranial random noise stimulation (hf-tRNS) can increase the excitability of the cortex beneath the stimulating electrode. Yet, it is unclear if hf-tRNS can modulate electroencephalographic FAA in patients with schizophrenia. We performed a randomized, double-blind, sham-controlled clinical trial to contrast hf-tRNS and sham stimulation for treating negative symptoms in 35 schizophrenia patients. We used electroencephalography to investigate if 10 sessions of hf-tRNS delivered twice-a-day for five consecutive weekdays would modulate electroencephalographic FAA in schizophrenia. EEG data were collected and FAA was expressed as the differences between common-log-transformed absolute power values of frontal right and left hemisphere electrodes in the alpha frequency range (8–12.5 Hz). We found that hf-tRNS significantly increased FAA during the first session of stimulation (p = 0.009) and at the 1-week follow-up (p = 0.004) relative to sham stimulation. However, FAA failed to predict and surrogate the improvement in the severity of negative symptoms with hf-tRNS intervention. Together, our findings suggest that modulating electroencephalographic frontal alpha asymmetry by using unidirectional hf-tRNS may play a key role in reducing negative symptoms in patients with schizophrenia.