Hearing voices in the head: Two meta-analyses on structural correlates of auditory hallucinations in schizophrenia

Past voxel-based morphometry (VBM) studies demonstrate reduced grey matter volume (GMV) in schizophrenia (SZ) patients' brains in various cortical and subcortical regions. Probably due to SZ symptoms' heterogeneity, these results are often inconsistent and difficult to integrate. We hypothesized that focusing on auditory verbal hallucinations (AVH) - one of the most common SZ symptoms - would allow reducing heterogeneity and discovering further compelling evidence of SZ neural correlates. We carried out two voxel-based meta-analyses of past studies that investigated the structural correlates of AVH in SZ. The review of whole-brain VBM studies published until June 2022 in PubMed and PsychInfo databases yielded (a) 13 studies on correlations between GMV and AVH severity in SZ patients (n = 472; 86 foci), and (b) 11 studies involving comparisons between hallucinating SZ patients (n = 504) and healthy controls (n = 524; 74 foci). Data were analyzed using the Activation Likelihood Estimation method. AVH severity was associated with decreased GMV in patients' left superior temporal gyrus (STG) and left posterior insula. Compared with healthy controls, hallucinating SZ patients showed reduced GMV on the left anterior insula and left inferior frontal gyrus (IFG). Our findings revealed important structural dysfunctions in a left lateralized cluster of brain regions, including the insula and temporo-frontal regions, that significantly contribute to the severity and persistence of AVH. Structural atrophy found in circuits involved in generating and perceiving speech, as well as in auditory signal processing, might reasonably be considered a biological marker of AVH in SZ.