Free-water imaging in subcortical gray matter in schizophrenia patients with persistent auditory verbal hallucinations

Abstract

Subcortical gray matter (SGM) is increasingly linked to the pathophysiology of schizophrenia, specifically auditory verbal hallucinations (AVHs). However, few studies have been conducted on the role of extracellular free-water (FW) and white matter microstructural abnormalities in AVHs within the SGM using the free water elimination technique. We conducted a comprehensive investigation of macroscopic volume, FW, and white matter microstructure in the SGM of 60 schizophrenia patients with persistent AVHs (p-AVH), 36 patients no AVH history (n-AVH), and 43 healthy control participants (HC). No macroscopic volume abnormalities were found in the p-AVH or n-AVH groups. However, abnormalities in both FW and microstructures were detected in multiple SGM structures of individuals with schizophrenia. Importantly, unlike the n-AVH group, the p-AVH group exhibited FW and microstructure abnormalities in the bilateral caudate that correlated with AVH severity. Our findings suggest that regardless of the presence of AVHs, FW and microstructure abnormalities in the SGM are more pronounced than macroscopic volume abnormalities in patients with schizophrenia. The bilateral caudate may be a key factor in the mechanisms underlying AVHs. Additionally, normal FW and microstructure in the bilateral caudate may be a notable characteristic of n-AVH patients.

Keywords: Free-water imaging; Persistent auditory verbal hallucinations; Schizophrenia; Subcortical gray matter.