Candidate Multimodal MRI Markers of Persistent Auditory Verbal Hallucinations: A Controlled Pilot Study

Background/Objectives: Auditory verbal hallucinations (AVH) are clinically heterogeneous experiences that may occur across psychiatric, neurological, sensory, and non-clinical contexts. This controlled pilot study investigated multimodal structural and functional MRI features associated with persistent AVH in a psychiatric clinical population, recruited from outpatient psychiatric clinics and diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder with psychotic features. Neurological, sensory, and non-clinical presentations of AVH were not included. Methods: This observational controlled pilot study included 14 participants with persistent auditory verbal hallucinations and 15 age- and sex-matched healthy controls. Participants with AVH had experienced the current persistent hallucinatory phase for a mean of 3.1 ± 1.6 years (range of 1-7), with a mean overall psychiatric illness duration of 12.4 ± 4.8 years. Independent component analysis assessed resting-state functional connectivity, BrainVoyager QX measured cortical thickness, and diffusion tensor imaging (DTI) evaluated white matter microstructure. Multiple comparisons were controlled using false discovery rate correction followed by 5000-iteration Monte Carlo cluster-extent correction for fMRI and Monte Carlo cluster correction for whole-brain structural metrics. Results: Participants with AVH demonstrated increased functional connectivity across default mode network (DMN) hubs (precuneus, inferior frontal, and parahippocampal gyri) and superior temporal regions. Whole-brain cortical thickness analysis revealed no significant group differences; however, secondary exploratory analyses of six regions previously implicated in AVH showed cortical thinning in participants with AVH relative to the controls after FDR correction. DTI revealed no group differences surviving whole-brain permutation correction (TFCE, FWE-corrected p < 0.05); exploratory uncorrected findings are reported as hypothesis-generating. Conclusions: This pilot study identifies structural and functional network differences between medicated individuals with persistent AVH and healthy controls, centred on frontotemporal and default mode networks. Because no psychiatric control group without AVH was included, these differences cannot be attributed specifically to AVH as opposed to the underlying psychiatric disorders or their treatment. No diffusion findings survived whole-brain permutation correction; exploratory uncorrected results are reported but are not incorporated into these conclusions. Collectively, these findings identify candidate imaging markers that require validation against psychiatric control groups.