Abnormal Local Activity and Functional Dysconnectivity in Patients with Schizophrenia Having Auditory Verbal Hallucinations

Auditory verbal hallucination (AVH) is emphasized as a pathological hallmark of schizophrenia. Neuroimaging studies provide evidence linking AVH to overlapping functional abnormalities in distributed networks. However, no clear conclusion has still been reached. This study aimed to further explore the brain activity of patients with schizophrenia having AVH from both local activity (LA) and functional connectivity (FC) insights, while excluding confounding factors from other positive symptoms. A total of 42 patients with AVH (AVH patients group, APG), 26 without AVH (non-AVH patients group, NPG), and 82 normal controls (NC) underwent resting-state functional magnetic resonance imaging (fMRI). LA measures, including regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFF), and FC measures were evaluated to understand the neuroimaging mechanism of AVH. APG showed increased ReHo and fALFF in the bilateral putamen (Put) compared with NPG and NC. FC analysis (using bilateral putamen as seeds) revealed that all patients showed abnormal FC of multiple resting-state network regions, including the anterior and post cingulate cortex, middle frontal gyrus, inferior parietal gyrus, and left angular gyrus. Interestingly, APG showed significantly decreased FC of insula extending to the superior temporal gyrus and inferior frontal gyrus compared with NPG and NC. The present findings suggested a significant correlation of abnormal LA and dysfunctional putamen-auditory cortical connectivity with the neuropathological mechanism of AVH, providing evidence for the functional disconnection hypothesis of schizophrenia.