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 crosscategory 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 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 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 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 structural 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. 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. Funding: None.

Grey matter morphometric biomarkers for classifying early schizophrenia and PD psychosis: a multicentre study

“…Brain regions of the best classifying networks (NW 8, 14, 18, 19, 23, 24, 28) include the middle temporal gyrus, postcentral gyrus, parahippocampal gyrus, hippocampus, precuneus, thalamus, n. accumbens, putamen, insula, temporal fusiform cortex, lateral occipital cortex, cerebellum crus I, II, cerebellum VIIb, VIIIa, frontal pole, and the Heschl’s gyrus. Again, these regions have been discussed reliably in the literature as core structures for functional and structural alterations in PD with psychotic symptoms (Bejr-kasem et al, 2021; Lenka et al, 2018, 2015; Pagonabarraga et al, 2014; Rollins et al, 2019; Vignando et al, 2022; Watanabe et al, 2013). There is a strong overlap in fairly well classifying regions between FEP and PDP, especially in the putamen, insula, hippocampus, parahippocampal gyrus precuneus, and thalamus.…”

Voices in Psychosis

“…Although 60-80% of people with a diagnosis of schizophrenia report hearing voices, this is also a trans-diagnostic human experience occurring in people with other clinical diagnoses such as Parkinson's disease, as well as in people with no psychiatric history whatsoever (Rollins et al, 2019). This has led researchers to understand voice-hearing as a dimensional phenomenon, occurring on a continuum from health to illness, which raises the question of whether there are common or distinct mechanisms in patient populations compared to people without a clinical diagnosis.…”

“…Using these techniques, neuroimaging studies have identified a number of brain regions involved in hearing voices and reality monitoring (see Image 26.1). These include: the medial prefrontal cortex (mPFC), implicated in processing and attributing self-referential information and attending to the mental states of oneself and others; the superior temporal gyrus (STG), involved in speech processing and language perception; the inferior frontal gyrus (IFG), involved in semantic processing and the activity of which during voice-hearing in individuals with schizophrenia correlates with the reported subjective reality of the voices; and the insula, involved in a range of subjective feelings, including self-awareness, which, together with the anterior cingulate cortex (ACC) region, constitutes a node in the brain's salience network that is associated with directing attention to important stimuli (Raij et al, 2009;Rollins et al, 2019Rollins et al, , 2020Zmigrod et al, 2016).…”

“…Much of the research undertaken to investigate the brain basis for hearing voices has focused on people with a diagnosis of schizophrenia. A recent meta-analysis and review of the brain structural correlates of the broader category of hallucinations across different sensory modalities and diagnoses has shown that psychiatric and neurological patients have distinct neuro-anatomical signatures (Rollins et al, 2019). This suggests there may be a plurality of neurobiological mechanisms responsible for the genesis of these perceptual experiences.…”

Structural brain abnormalities in schizophrenia patients with a history and presence of auditory verbal hallucination

“…Auditory verbal hallucination (AVH) is a cardinal feature of schizophrenia; in AVH, patients hear voices without the presence of corresponding external stimuli [1]. A number of magnetic resonance imaging (MRI) studies have compared the brain morphology of schizophrenia patients with and without AVH, and their findings suggest the presence of structural and functional alterations in regions such as the superior temporal gyrus, hippocampus, insula, anterior cingulate, inferior frontal gyrus, and inferior temporal gyrus in those with AVH [2][3][4][5].…”