Metacognitive Training Modulates Default-Mode Network Homogeneity During 8-Week Olanzapine Treatment in Patients With Schizophrenia

Background: Previous studies have revealed the efficacy of metacognitive training for schizophrenia. However, the underlying mechanisms of metacognitive training on brain function alterations, including the default-mode network (DMN), remain unknown. The present study explored treatment effects of metacognitive training on functional connectivity of the brain regions in the DMN. Methods: Forty-one patients with schizophrenia and twenty healthy controls were scanned using resting-state functional magnetic resonance imaging. Patients were randomly assigned to drug plus psychotherapy (DPP) and drug therapy (DT) groups. The DPP group received olanzapine and metacognitive training, and the DT group received only olanzapine for eight weeks. Network homogeneity (NH) was applied to analyze the imaging data, and pattern classification techniques were applied to test whether abnormal NH deficits at baseline might be used to discriminate patients from healthy controls. Abnormal NH in predicting treatment response was also examined in each patient group. Results: Compared with healthy controls, patients at baseline showed decreased NH in the bilateral ventral medial prefrontal cortex (MPFC), right posterior cingulate cortex (PCC)/precuneus, and bilateral precuneus and increased NH in the right Cerebellum Crus II and bilateral superior MPFC. NH values in the right PCC/precuneus increased in the DPP group after eight weeks of treatment, whereas no substantial difference in NH value was observed in the DT group. Support vector machine analyses showed that the accuracy, sensitivity, and specificity for distinguishing patients from healthy controls were more than 0.7 in the NH values of the right PCC/precuneus, bilateral ventral MPFC, bilateral superior MPFC, and bilateral precuneus regions. Support vector regression analyses showed that high NH levels at baseline in the bilateral superior MPFC could predict symptomatic improvement of positive and negative syndrome scale (PANSS) after eight weeks of DPP treatment. No correlations were found between alterations in the NH values and changes in the PANSS scores/cognition parameters in the patients. Conclusion: This study provides evidence that metacognitive training is related to the modulation of DMN homogeneity in schizophrenia.