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Energy Landscape and Dynamic State Modeling for Schizophrenia Biomarker Extraction in Task-Based fMRI

Allen, J.; Hong, L. E.; Choa, F.-S.

2025-12-15 radiology and imaging
10.64898/2025.12.14.25342238 medRxiv
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Task-based functional magnetic resonance imaging (fMRI) examines how the brain dynamically responds to cognitive and perceptual demands, offering complementary insight beyond traditional activation-based analyses in schizophrenia. Prior task-based fMRI studies have identified reduced functional connectivity within auditory and associated cortical areas. In this study, we investigated task-evoked functional connectivity and brain state dynamics in 25 healthy controls, 23 patients with schizophrenia experiencing auditory verbal hallucinations (AVH+), and 23 patients without hallucinations (AVH-). Participants completed multiple auditory paradigms, including word lists, sentence lists, and reverse speech. The most robust connectivity differences emerged during the word list task, where cluster-level analyses revealed distinct network interaction patterns differentiating controls, AVH+, and AVH-patients. Energy landscape modeling further demonstrated altered stability and organization of brain states in both patient groups, with the largest deviations observed in AVH+ individuals. These alterations point to dysregulated neural dynamics linked to hallucination vulnerability. Overall, the results show that task-based fMRI sensitively captures disruptions in functional connectivity and brain state stability relevant to auditory hallucinations, underscoring its value for characterizing network-level mechanisms underlying perceptual disturbances in schizophrenia.

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