Effects of 40 Hz transcranial alternating current stimulation on neural synchronization and cognitive correlates in schizophrenia: An EEG study

Gamma-band neural oscillations are critically involved in working memory and are disrupted in schizophrenia. Transcranial alternating current stimulation (tACS) at gamma frequency is a promising noninvasive approach to restore oscillatory synchrony and enhance cognition. This randomized, double-blind trial tested whether 40 Hz tACS targeting frontoparietal networks modulates gamma-band activity and connectivity during working memory, and whether these electrophysiological changes relate to cognition in schizophrenia. Patients with schizophrenia (n = 33) were randomized to 10 sessions of active or sham tACS over the left dorsolateral prefrontal cortex (F3) and right parietal cortex (P4), with cognition assessed using standardized neurocognitive measures (MATRICS Consensus Cognitive Battery, MCCB) and an n-back working-memory task. EEG during an n-back task was recorded pre- and post-intervention to assess gamma power, phase-locking value (PLV), and phase-amplitude coupling (PAC). A significant Group × Time interaction indicated that 1-back minus 0-back PLV increased in the active group but not in sham (P = 0.048, Cohen's d = 1.08). For PAC, a significant interaction showed that delta-high gamma coupling at F3 remained stable in the active group but declined in sham (P = 0.036, Cohen's d = 1.00). There was no significant correlation with n-back measures of working memory, but an exploratory significant finding linking this modulation to visual learning at 4-week follow-up. No significant group differences were found for MCCB total scores; however, a significant Group × Time interaction emerged for 0-back accuracy during EEG recording (P = 0.029, Cohen's d = 1.19). These findings demonstrate that 40 Hz tACS can enhance and preserve gamma synchrony in frontoparietal circuits during working memory. The maintained delta-gamma coupling in our exploratory findings on visual learning may suggest a relationship to sustained improvements in cognition over time, but needs additional confirmation.