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

Area of Science:

• Neuroscience
• Psychiatry
• Medical Imaging

Background:

• Schizophrenia is a severe neuropsychiatric disorder with ongoing research into its biological underpinnings.
• Non-invasive neuroimaging methods like resting-state functional magnetic resonance imaging (rsfMRI) are crucial for identifying diagnostic markers.
• Existing frameworks for schizophrenia-associated functional connectivity need larger sample sizes and better accounting for individual variability and clinical factors.

Purpose of the Study:

• To identify reliable neuroimaging markers for schizophrenia using a large-scale, multi-site rsfMRI dataset.
• To refine theoretical frameworks of brain connectivity in schizophrenia by examining relationships with clinical variables.
• To develop an open-source, high-fidelity template of schizophrenia-related functional network connectivity (FNC).

Main Methods:

• Employed a data-driven, whole-brain approach on a large rsfMRI dataset (N=2,656; schizophrenia=1,248).
• Utilized reference-guided independent component analysis (ICA) to generate subject-specific FNC and identify schizophrenia patterns.
• Modeled associations between clinical variables (medication, age of onset, chronicity, symptoms, cognition) and FNC.

Main Results:

• Identified a reliable schizophrenia-FNC signature with stronger negative cerebellothalamic and positive thalamocortical connectivity.
• Implicated sensory, motor, and associative cortical circuits in the observed connectivity disruptions.
• Found that while medication and chronicity influenced FNC, cerebellothalamic disruptions remained a robust schizophrenia marker.

Conclusions:

• This study represents the largest schizophrenia-specific rsfMRI investigation to date.
• The findings provide a nuanced map of brain connectivity in schizophrenia, detailing interactions with clinical variables.
• An open-source template of schizophrenia-related connectivity has been released to promote reproducibility and biomarker development.