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

Abstract

BACKGROUND: Hallucinations are transmodal and transdiagnostic phenomena, occurring across sensory modalities 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 voxelwise meta-analyses of hallucination status across diagnoses using 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 abstracts were identified. Patients with 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 fusiform gyrus, right thalamus, and right lateral occipital gyrus. Group differences between meta-analyses were formally confirmed and a jackknife sensitivity analysis established the reproducibility of results across nearly all study combinations. For other measures (28 studies), the most consistent findings associated with hallucination status were reduced cortical thickness in temporal gyri in schizophrenia and altered hippocampal volume in Parkinson's disease and dementia. 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. Funding: None. Declaration of Interest: Ms. Rollins reports a scholarship from Gates Cambridge during the conduct of the study. Professor Rowe reports grants from Wellcome Trust during the conduct of the study, grants from NIHR, McDonnell Foundation, PSP Association, Parkinsons UK, Medical Research Council, Evelyn Trust, and AZ-Medimmune, personal fees from Asceneuron, and other from Guarantors of Brain outside the submitted work. Professor Suckling, Dr. Murray, Dr. Garrison, Dr. Simons, and Dr. O’Callaghan have nothing to disclose.