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

Abstract

Purpose Auditory 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 Methods Eighteen 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. Results Granger 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. Conclusion Our 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.

Domain-general and domain-specific functional networks of Broca’s area underlying language processing

“…Structural connectivity research identified various white-matter pathways including the superior longitudinal fasciculus (arcuate fasciculus), middle longitudinal fasciculus, inferior fronto-occipital fasciculus, extreme capsule, external capsule and uncinate fasciculus that connect Broca’s area with the superior and middle temporal gyri as well as with the inferior parietal lobe (supramarginal and angular gyri) (Axer, Klingner, & Prescher, 2013; Glasser & Rilling, 2008; Kellmeyer et al, 2013; Parker et al, 2005; Powell et al, 2006; Saur et al, 2010). Studies of effective connectivity of Broca’s area also delineated functional connectivity profile of this region both during resting state (Gao et al, 2020), and during various tasks including inhibitory control (Guha et al, 2020), speech production (Eickhoff, Heim, Zilles, & Amunts, 2009) and language processing (den Ouden et al, 2012; Schmithorst, Holland, & Plante, 2007; Sonty et al, 2007), highlighting the causal associations between Broca’s area and various cortical and subcortical regions. Importantly, this body of research underscored the connection between Broca’s area and the posterior superior temporal cortex (Wernicke’s area), providing convergent evidence, together with structural connectivity findings, for the primary role of this loop for language processing (den Ouden et al, 2012; Schmithorst et al, 2007; Sonty et al, 2007).…”

Domain‐general and domain‐specific functional networks of Broca's area underlying language processing

“…Structural connectivity research identified various white matter pathways including the superior longitudinal fasciculus (arcuate fasciculus), middle longitudinal fasciculus, inferior fronto‐occipital fasciculus, extreme capsule, external capsule, and uncinate fasciculus that connect Broca's area with the superior and middle temporal gyri as well as with the inferior parietal lobe (supramarginal and angular gyri) (Axer et al., 2013 ; Glasser & Rilling, 2008 ; Kellmeyer et al., 2013 ; Parker et al., 2005 ; Powell et al., 2006 ; Saur et al., 2010 ). Studies of the effective connectivity of Broca's area also delineated the functional connectivity profile of this region both during resting state (Gao et al., 2020 ), and during various tasks including inhibitory control (Guha et al., 2020 ), speech production (Eickhoff et al., 2009a ), and language processing (den Ouden et al., 2012 ; Schmithorst et al., 2007 ; Sonty et al., 2007 ), highlighting the causal associations between Broca's area and various cortical and subcortical regions. Importantly, this body of research underscored the connection between Broca's area and the posterior superior temporal cortex (Wernicke's area), providing convergent evidence, together with structural connectivity findings, for the primary role of this loop for language processing (den Ouden et al., 2012 ; Schmithorst et al., 2007 ; Sonty et al., 2007 ).…”

Different Features of Metabolic Connectivity Map and Granger Causality Method in Revealing Directed Dopamine Pathways: A Pilot Study Based on Integrated PET/MR

“…The effective connectivity (EC), which gives the directional or causal relationships among brain regions is more important for the exploration of the underlying brain mechanisms [2]. The understanding of the directionality of brain networks provides insights into the diagnosis and treatment of neurological or mental diseases such as Alzheimer's disease [3], schizophrenia [4] and addiction [5] etc.…”