Increased regional homogeneity modulated by metacognitive training predicts therapeutic efficacy in patients with schizophrenia

Abstract

Previous studies have demonstrated the efficacy of metacognitive training (MCT) in schizophrenia. However, the underlying mechanisms related to therapeutic effect of MCT remain unknown. The present study explored the treatment effects of MCT on brain regional neural activity using regional homogeneity (ReHo) and whether these regions' activities could predict individual treatment response in schizophrenia. Forty-one patients with schizophrenia and 20 healthy controls were scanned using resting-state functional magnetic resonance imaging. Patients were randomly divided into drug therapy (DT) and drug plus psychotherapy (DPP) groups. The DT group received only olanzapine treatment, whereas the DPP group received olanzapine and MCT for 8 weeks. The results revealed that ReHo in the right precuneus, left superior medial prefrontal cortex (MPFC), right parahippocampal gyrus and left rectus was significantly increased in the DPP group after 8 weeks of treatment. Patients in the DT group showed significantly increased ReHo in the left ventral MPFC/anterior cingulate cortex (ACC), left superior MPFC/middle frontal gyrus (MFG), left precuneus, right rectus and left MFG, and significantly decreased ReHo in the bilateral cerebellum VIII and left inferior occipital gyrus (IOG) after treatment. Support vector regression analyses showed that high ReHo levels at baseline in the right precuneus and left superior MPFC could predict symptomatic improvement of Positive and Negative Syndrome Scale (PANSS) after 8 weeks of DPP treatment. Moreover, high ReHo levels at baseline and alterations of ReHo in the left ventral MPFC/ACC could predict symptomatic improvement of PANSS after 8 weeks of DT treatment. This study suggests that MCT is associated with the modulation of ReHo in schizophrenia. ReHo in the right precuneus and left superior MPFC may predict individual therapeutic response for MCT in patients with schizophrenia.

Keywords: Metacognitive training; Olanzapine; Regional homogeneity; Schizophrenia; Support vector regression.

Fig. 1

Brain regions with significant difference in ReHo between all patients at baseline and healthy controls. Brain regions with significant difference were observed in the bilateral ventral MPFC, left superior MPFC, right ITG, left triangular IFG, right precuneus, left SMA, left middle FG, left cerebellum VIII, left cerebellum X, right triangular IFG, left superior TG, left superior FG, and right superior parietal gyrus. The color bar represents the t values of the group analysis of ReHo. ReHo regional homogeneity, MPFC medial prefrontal cortex, SMA supplementary motor area, ITG inferior temporal gyrus, IFG inferior frontal gyrus

Fig. 2

Treatment effects on ReHo in the DPP group. Brain regions with significant difference in ReHo were observed in the right precuneus, left superior MPFC, right parahippocampal gyrus, and left rectus after 8 weeks of treatment. The color bar represents the t values of the group analysis of ReHo. DPP drug plus psychotherapy, ReHo regional homogeneity, MPFC medial prefrontal cortex

Fig. 3

Treatment effects on ReHo in the DT group. Brain regions with significant difference in ReHo were observed in the left superior MPFC/ MFG, left ventral MPFC /ACC, left precuneus, right rectus, left MFG, left IOG and bilateral cerebellum VIII after treatment. The color bar represents the t values of the group analysis of ReHo. DT drug therapy, ReHo regional homogeneity, MPFC medial prefrontal cortex, ACC anterior cingulate cortex, MFG middle frontal gyrus, IOG inferior occipital gyrus

Fig. 4

Correlations between ReHo and PANSS scores/cognitive scores in the patients. A: correlations between alterations of ReHo in the right precuneus and changes in PANSS negative symptoms subscale scores in the DPP group after 8 weeks of treatment. B: correlations between alterations of ReHo in the left precuneus and changes in BACS scores in the DT group after 8 weeks of treatment. C: correlations between increased ReHo in the left superior TG and CPTIP scores in all patients (both DPP and DT groups) at baseline. DPP drug plus psychotherapy, DT drug therapy, ReHo regional homogeneity, PANSS Positive and Negative Syndrome Scale; TG temporal gyrus, BACS Brief Assessment of Cognition in Schizophrenia, CPTIP Continuous Performance Test-identical Pairs

Fig. 5

SVR results suggested that high ReHo levels at baseline in the left superior MPFC could predict therapeutic response in the DPP group. Left: SVR parameter selection results (3D visualization); Right: The positive correlations between predicted and actual RR of the PANSS positive symptoms subscale scores(r = 0.891, P <  0.0001), general symptoms subscale scores (r = 0.703, P = 0.000785) of individual patients after 8 weeks of DPP treatment. DPP drug plus psychotherapy, ReHo regional homogeneity, SVR support vector regression, MPFC medial prefrontal cortex, PANSS Positive and Negative Syndrome Scale, RR reduction ratio

Fig. 6

SVR results suggested that high ReHo levels at baseline in the right precuneus could predict therapeutic response in the DPP group. Left: SVR parameter selection results (3D visualization); right: the positive correlations between predicted and actual RR of the PANSS total scores (r = 0.688, P = 0.001136) of individual patients after 8 weeks of DPP treatment. DPP drug plus psychotherapy, ReHo regional homogeneity, SVR support vector regression, PANSS Positive and Negative Syndrome Scale, RR reduction ratio