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

Xiaoxiao Shan, Rongyuan Liao, Yangpan Ou, Yudan Ding, Feng Liu, Jindong Chen, Jingping Zhao, Wenbin Guo, Yiqun He, Xiaoxiao Shan, Rongyuan Liao, Yangpan Ou, Yudan Ding, Feng Liu, Jindong Chen, Jingping Zhao, Wenbin Guo, Yiqun He

Abstract

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 20 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 8 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 8 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 8 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.

Keywords: default-mode network; metacognitive training; network homogeneity; olanzapine; schizophrenia.

Copyright © 2020 Shan, Liao, Ou, Ding, Liu, Chen, Zhao, Guo and He.

Figures

Figure 1
Figure 1
The consort flow diagram for the present study.
Figure 2
Figure 2
PANSS and cognitive tests results across different time points. Values above histogram bars represent related group means. Bars represent related SD. PANSS, Positive and Negative Syndrome Scale; TMT-A, Trail Making Test, part A; BACS-SC, Brief Assessment of Cognition in Schizophrenia Symbol Coding Test; HVLT-R, Hopkins Verbal Learning Test-Revised; WMS-SS, Wechsler Memory Scale Spatial Span; NAB-M, Neuropsychological Assessment Battery-Mazes; BVMT-R, Brief Visuospatial Memory Test-Revised; CF-ANF, Category Fluency-Animal Naming Fluency; MSCIT, Mayer-Salovey-Caruso Emotional Intelligence Test; CPT-IP, Continuous Performance Test-identical Pairs. (A) Cognitive results across different time points in the DPP group. (B) Cognitive results across different time points in the DT group. (C) PANSS total scores and subscale scores across different time points in the two groups.
Figure 3
Figure 3
Brain regions with significant difference in DMN NH between patients and healthy controls at baseline. The color bar represents the t values of the group analysis of NH. Left: DPP group vs healthy controls. Brain regions with significant difference were observed in the right Cerebellum Crus II, bilateral ventral MPFC, right Precuneus/PCC, and bilateral superior MPFC. Right: DT group vs healthy controls. Brain regions with significant difference were observed in the bilateral ventral MPFC, right Precuneus/PCC, bilateral Precuneus, and bilateral superior MPFC. DPP, drug plus psychotherapy; DT, drug therapy; DMN, default-mode network; NH, network homogeneity; MPFC, medial prefrontal cortex; PCC, posterior cingulate cortex.
Figure 4
Figure 4
Imaging results across different time points. Values above histogram bars represent related group means. Bars represent related SD. (A) The NH values of brain regions across patients in the DT group and controls at baseline. (B) The NH values of brain regions across patients in the DPP group and controls at baseline. (C) The NH values of brain regions in the DPP group from baseline to 8 weeks.
Figure 5
Figure 5
Treatment effects of DMN NH across patients at two point (at baseline and after 8 weeks of treatment). The color bar represents the t value of the group analysis of NH. Left: DPP group from baseline to 8 weeks. Brain regions with significant difference in the NH values were observed in the right Precuneus/PCC. Right: DT group vs DPP group at 8 weeks. Brain regions with significant difference in the NH value were observed in the bilateral Precuneus.
Figure 6
Figure 6
Correlations between the NH values of the bilateral Precuneus and the BVMTR scores in patients after 8 weeks of treatment.
Figure 7
Figure 7
Using decreased NH values in the right PCC/precuneus to differentiate the patients (DPP group) from the controls. Visualization of classifications through support vector machine (SVM) using the NH values in the significantly different regions. Left: SVM parameters selection result of 3D view; Right: Classified map of the NH values in the right PCC/precuneus. SVM, support vector machine.
Figure 8
Figure 8
Using decreased NH values in the bilateral ventral MPFC to differentiate the patients (DPP group) from the controls. Visualization of classifications through support vector machine (SVM) using the NH values in the significantly different regions. Left: SVM parameters selection result of 3D view; Right: Classified map of the NH values in the bilateral ventral MPFC.
Figure 9
Figure 9
SVR results suggested that the high NH levels at baseline in the bilateral 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 general symptoms subscale scores (r=0.830, p
All figures (9)

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