Inter- and intra-hemispheric lateralization alterations in auditory verbal hallucinations of Schizophrenia: insights from resting-state functional connectivity.

Auditory verbal hallucinations (AVHs) in schizophrenia are hypothesized to involve alterations in hemispheric lateralization, but the specific neural mechanisms remain unclear. This study investigated functional intra- and inter-hemispheric connectivity to identify lateralization patterns unique to AVHs. Resting-state fMRI data were collected from 60 schizophrenia patients with persistent AVHs (p-AVH group), 39 patients without AVHs (n-AVH group), and 59 healthy controls (HC group). Using a homotopic atlas, we quantified lateralization indices of functional segregation and integration across 200 homotopic ROI pairs. Segregation was defined as the degree of preferential intra-hemispheric communication within each hemisphere versus inter-hemispheric communication. Integration was used to assess the extent of inter-hemispheric communication between the two hemispheres. Our findings revealed a significant rightward lateralization of segregation in two lateral prefrontal cortex homotopic pairs in the p-AVH group. Additionally, we observed a leftward lateralization of integration in an inferior parietal lobule homotopic pair within the temporoparietal junction region, specifically in the p-AVH group. Importantly, the lateralization index of segregation in the prefrontal cortex was negatively correlated with AVH severity, indicating that greater rightward lateralization is associated with more severe AVHs. These lateralization changes were absent when comparing the n-AVH group to HC group, suggesting they are unique to AVHs in schizophrenia. Our results underscore the pivotal role of altered hemispheric lateralization of functional segregation and integration in the etiology of AVHs, providing new insights into the neural mechanisms underlying these symptoms.