Altered Effective Connectivity in Schizophrenic Patients With Auditory Verbal Hallucinations: A Resting-State fMRI Study With Granger Causality Analysis.

Xiaoyan Lei,Min Tang,Lei Wang,Yarong Wang,Jie Gao,Wei Wang,Jian Yang,Yajuan Fan,Dongsheng Zhang,Xin Zhang,Xiaoling Zhang

doi:10.3389/fpsyt.2020.00575

Abstract

PurposeAuditory verbal hallucinations (AVH) are among the most common and prominent symptoms of schizophrenia. Although abnormal functional connectivity associated with AVH has been reported in multiple regions, the changes in information flow remain unclear. In this study, we aimed to elucidate causal influences related to AVH in key regions of auditory, language, and memory networks, by using Granger causality analysis (GCA).Patients and MethodsEighteen patients with schizophrenia with AVH and eighteen matched patients without AVH who received resting-state fMRI scans were enrolled in the study. The bilateral superior temporal gyrus (STG), Broca’s area, Wernicke’s area, putamen, and hippocampus were selected as regions of interest.ResultsGranger causality (GC) increased from Broca’s area to the left STG, and decreased from the right homolog of Wernicke’s area to the right homolog of Broca’s area, and from the right STG to the right hippocampus in the AVH group compared with the non-AVH group. Correlation analysis showed that the normalized GC ratios from the left STG to Broca’s area, from the left STG to the right homolog of Broca’s area, and from the right STG to the right homolog of Broca’s area were negatively correlated with severity of AVH, and the normalized GC ratios from Broca’s area to the left hippocampus and from Broca’s area to the right STG were positively correlated with severity of AVH.ConclusionOur findings indicate a causal influence of pivotal regions involving the auditory, language, and memory networks in schizophrenia with AVH, which provide a deeper understanding of the neural mechanisms underlying AVH.

Highlights

Auditory verbal hallucinations (AVH) are the most prominent and burdensome symptoms of schizophrenia, and comprise sensory experiences wherein voices are heard without a causative external stimulus
Compared with the non-AVH group, AVH group showed an increase in granger causality (GC) from the right homolog of Broca’s area to the left STG, and a decrease from the right STG to the right hippocampus, from the left putamen to the right hippocampus, from the right putamen to the right hippocampus, and from the right putamen to Broca’s area (Tables 2 and 3)
The normalized ratios of GC from the left STG to Broca’s area and its right homolog, from the right STG to the right homolog of Broca’s area, and from the right STG to the right hippocampus were significantly lower in the AVH group than in the non-AVH group

Summary

Introduction

Auditory verbal hallucinations (AVH) are the most prominent and burdensome symptoms of schizophrenia, and comprise sensory experiences wherein voices are heard without a causative external stimulus. In 30% of patients with AVH, the hallucinations are not affected by clinical treatments [3], and cause functional disability and lower quality of life. The mechanism by which AVH occurs spontaneously from the brain’s intrinsic activity is of great clinical interest. Restingstate functional magnetic resonance imaging (fMRI) can show spontaneous brain activity in vivo, and can provide invaluable insights into the psychopathology of AVH. Based on time series derived from resting state fMRI data, functional connectivity (FC) analysis can be used to calculate the temporal correlations between a blood-oxygenation-level dependent in any two regions, offering an effective method to study alterations in brain connectivity within multiple brain networks associated with AVH in schizophrenia

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