Network Localization of State and Trait of Auditory Verbal Hallucinations in Schizophrenia

Abstract

BACKGROUND AND HYPOTHESIS: Neuroimaging studies investigating the neural substrates of auditory verbal hallucinations (AVH) in schizophrenia have yielded mixed results, which may be reconciled by network localization. We sought to examine whether AVH-state and AVH-trait brain alterations in schizophrenia localize to common or distinct networks. STUDY DESIGN: We initially identified AVH-state and AVH-trait brain alterations in schizophrenia reported in 48 previous studies. By integrating these affected brain locations with large-scale discovery and validation resting-state functional magnetic resonance imaging datasets, we then leveraged novel functional connectivity network mapping to construct AVH-state and AVH-trait dysfunctional networks. STUDY RESULTS: The neuroanatomically heterogeneous AVH-state and AVH-trait brain alterations in schizophrenia localized to distinct and specific networks. The AVH-state dysfunctional network comprised a broadly distributed set of brain regions mainly involving the auditory, salience, basal ganglia, language, and sensorimotor networks. Contrastingly, the AVH-trait dysfunctional network manifested as a pattern of circumscribed brain regions principally implicating the caudate and inferior frontal gyrus. Additionally, the AVH-state dysfunctional network aligned with the neuromodulation targets for effective treatment of AVH, indicating possible clinical relevance. CONCLUSIONS: Apart from unifying the seemingly irreproducible neuroimaging results across prior AVH studies, our findings suggest different neural mechanisms underlying AVH state and trait in schizophrenia from a network perspective and more broadly may inform future neuromodulation treatment for AVH.