42.3 MICROSTRUCTURAL WHITE MATTER ABNORMALITIES ASSOCIATED WITH AUDITORY VERBAL HALLUCINATIONS
Marek R. Kubicki, Maria Angelique Di Biase, Suheyla Cetin Karayumak, Thomas J. Whitford, René C.W. Mandl, Martha E. Shenton, Iris E. Sommer, Ofer Pasternak · Schizophrenia Bulletin · 2019
Auditory verbal hallucinations (AVH) are one of the hallmarks of psychosis, but they also appear in 5–10 % of healthy individuals. Structural and functional imaging studies implicate the superior temporal gyrus and inferior frontal language areas in generation of AVH. Here, we examined white matter in tracts interconnecting these regions with advanced diffusion imaging methods. We aimed to reveal pathophysiologic substrates for AVH across several datasets, consisting of first episode and chronic schizophrenia patients as well as healthy individuals with and without AVH. Diffusion MRI data were analyzed using diffusion tractography to extract fiber connections forming language networks: arcuate fasciculus (AF), inferior occipito-frontal fasciculus (IFOF), and the genu and isthmus of the corpus callosum (CC). Several measures of white matter microstructure were averaged over these white matter structures, including extracellular free water (FW) and tissue-specific fractional anisotropy (FAt), axial and radial diffusivity (ADt, RDt). Measures were compared between patients with and without hallucinations, and healthy, non-hallucinating controls across multiple datasets (total of 650 healthy controls and 550 patients at various stages of schizophrenia). We identified significant microstructural abnormalities in language connections across patients with established schizophrenia and healthy individuals with AVH, albeit to lesser degree. These changes were characterized by increased extracellular FW and RDt, as well as decreased FAt. Notably, microstructural variability was associated with positive symptoms and AVH, independent of diagnostic status and illness stage (first episode and chronic schizophrenia). Our data point to shared neural substrates for auditory verbal hallucinations across heterogeneous schizophrenia populations and healthy individuals; compatible with dimensional models of psychosis.