Meta-analytic Evidence for the Plurality of Mechanisms in Transdiagnostic Structural MRI Studies of Hallucination Status

Background: Hallucinations are transmodal and transdiagnostic phenomena, occurring across sensorymodalities and presenting in psychiatric, neurodegenerative, neurological, and non-clinical populations. Despite their cross-category occurrence, little empirical work has directly compared between-group neural correlates of hallucinations. Methods: We performed whole-brain voxelwisemeta-analyses of hallucination status across diagnoses using anisotropic effect-size seed-based d mapping (AES-SDM), and conducted a comprehensive systematic review in PubMed and Web of Science until May 2018 on other structural correlates of hallucinations, including cortical thickness and gyrification. Findings: 3214 abstractswere identified. Patientswith psychiatric disorders and hallucinations (eight studies) exhibited reduced gray matter (GM) in the left insula, right inferior frontal gyrus, left anterior cingulate/paracingulate gyrus, left middle temporal gyrus, and increased in the bilateral fusiform gyrus, while patients with neurodegenerative disorders with hallucinations (eight studies) showed GM decreases in the left lingual gyrus, right supramarginal gyrus/parietal operculum, left parahippocampal gyrus, left fusiformgyrus, right thalamus, and right lateral occipital gyrus. Group differences between psychiatric and neurodegenerative hallucination meta-analyses were formally confirmed using Monte Carlo randomizations to determine statistical significance, and a jackknife sensitivity analysis established the reproducibility of results across nearly all study combinations. For other structuralmeasures (28 studies), the most consistent findings associated with hallucination statuswere reduced cortical thickness in temporal gyri in schizophrenia and altered hippocampal volume in Parkinson's disease and dementia. Additionally, increased severity of hallucinations in schizophrenia correlated with GM reductions within the left superior temporal gyrus, right middle temporal gyrus, bilateral supramarginal and angular gyri. Interpretation: Distinct patterns of neuroanatomical alteration characterize hallucination status in patients with psychiatric and neurodegenerative diseases, suggesting a plurality of anatomical signatures. This approach has implications for treatment, theoretical frameworks, and generates refutable predictions for hallucinations in other diseases and their occurrence within the general population. (C) 2019 Published by Elsevier Ltd.