Altered effective brain connectivity at early response of antipsychotics in first-episode schizophrenia with auditory hallucinations

Objective This study aimed to examine the alterations of cortical connectivity in first-episode schizophrenia (FES) with auditory hallucinations at early response of antipsychotics. Methods This was a nonexperimental control of medication study. We measured the cortical activity of 20 medicated patients with FES (medicated group), 19 nonmedicated patients with FES (nonmedicated group), and 22 healthy controls using electroencephalogram during eye-open resting state. Source reconstruction analysis was performed to determine the brain regions that showed significant group difference. A dynamic causal modelling (DCM) analysis was used to estimate the effective connectivity between sources. Result Both FES groups expressed increased activity in the right middle frontal gyrus (RMFG) and left/right superior temporal gyrus (L/RSTG) relative to that in the controls (p < 0.05), and the nonmedicated group presented even higher activity than the medicated group (p < 0.05). The effective connectivity from RMFG to LSTG was weaker in the nonmedicated group relative to that in the medicated group (p < 0.01), although patients in the medicated group showed no difference with healthy controls in RMFG to L/RSTG connections. The Bayesian model selection analysis found modulatory lateralization in the nonmedicated group. Conclusion The patients with FES showed frontotemporal hyperactivity and disconnectivity. The effective connections accompanied with modulation were improved when hallucination diminished at early response of routine medication. Significance This study provided the first evidence of early drug response-related alterations in effective brain connectivity.