NeuroMark-SZ: A Holistic Resting-State-fMRI-Based Model for Divergent Functional Circuitry in Schizophrenia

A reliable schizophrenia rsfMRI functional connectivity signature shows aberrantly stronger negative cerebellothalamic and positive thalamocortical connectivity in a multi-site dataset (N = 2,656; schizophrenia = 1,248).

• Why it matters: Prior resting-state connectivity frameworks are limited by smaller samples, confirmation bias, and incomplete handling of individual variability, medication effects, and chronicity.
• What they did: Using reference-guided ICA, the study derived subject-specific whole-brain FNC and modeled links to medication dosage, age of onset, chronicity, symptom severity, and cognitive performance.
• The result: Medication and chronicity were significantly associated with these signatures, but core cerebellothalamic disruptions remained robust, enabling a high-fidelity open-source template for schizophrenia biomarker development.