Abstract

Although the default mode network (DMN) is known to be abnormal in schizophrenia (SZ) patients with auditory verbal hallucinations (AVHs), it is still unclear whether AVHs that occur in SZ are associated with certain information flow in the DMN. This study collected resting-state functional magnetic resonance imaging data from 28 first-episode, drug-naïve SZ patients with AVHs, 20 SZ patients without AVHs, and 38 healthy controls. We used Granger causality analysis (GCA) to examine effective connectivity (EC) of two hub regions [posterior cingulate cortex (PCC) and anteromedial prefrontal cortex (aMPFC)] within the DMN. We used two-sample t-tests to compare the difference in EC between the two patient groups, and used Spearman correlation analysis to characterize the relationship between imaging findings and clinical assessments. The GCA revealed that, compared with the non-AVHs group, EC decreased from aMPFC to left inferior temporal gyrus (ITG) and from PCC to left cerebellum posterior lobe, ITG, and right middle frontal gyrus in SZ patients with AVHs. We also found significant correlations between clinical assessments and mean strengths of connectivity from aMPFC to left ITG and from PCC to left ITG. Moreover, receiver operating characteristic analysis revealed that the above-mentioned effective connectivities had a diagnostic value for distinguishing SZ patients with AVHs from non-AVHs patients. These findings suggest that AVHs in SZ patients may be associated with the aberrant information flows of the DMN, and the left ITG may probably serve as a potential biomarker for the neural mechanisms underlying AVHs in SZ patients.

Highlights

  • Auditory verbal hallucinations (AVHs), a symptom that appears to be very pragmatic and is sensitive to the perceptions of sound that occur without corresponding external stimuli, have been demonstrated to exist in 60−90% of schizophrenia (SZ) cases (Alderson-Day et al, 2016)

  • (2) The effects of head motion: Using the statistical analysis accounting for the ‘scrubbing’ procedure in preprocessed images (Power et al, 2012; Yan et al, 2013), we found that the main results in effective connectivity (EC) from anteromedial prefrontal cortex (aMPFC) to inferior temporal gyrus (ITG) and from posterior cingulate cortex (PCC) to both ITG and middle frontal gyrus (MFG) survived (Alphasim corrected P < 0.05) (Figure 4). (3) The effects of global signal removal: With the global signal removed, the auditory verbal hallucinations (AVHs) group showed significantly decreased EC from aMPFC to ITG

  • The non-AVHs group displayed reduced EC from aMPFC to right cingulate gyrus and left insula and from left superior temporal gyrus to PCC and enhanced EC from left cingulate gyrus, right thalamus, and right putamen to aMPFC relative to healthy control subjects (HCs)

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Summary

Introduction

Auditory verbal hallucinations (AVHs), a symptom that appears to be very pragmatic and is sensitive to the perceptions of sound that occur without corresponding external stimuli, have been demonstrated to exist in 60−90% of schizophrenia (SZ) cases (Alderson-Day et al, 2016). Several studies have examined brain activation in SZ patients with AVHs or hallucination predisposition (Allen et al, 2012; Alderson-Day et al, 2015, 2016). Default mode network (DMN), one of the most well-known RSNs, seems to play a prominent role in SZ patients (Menon, 2011; Woodward et al, 2011). This largescale brain network comprises anteromedial prefrontal cortex (aMPFC), posterior cingulate cortex (PCC), and medial temporal lobe including the hippocampus and the lateral temporoparietal area (Buckner et al, 2008). The variety of results might be related to many factors such as patient characteristics or methodological approaches employed in the analyses

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