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    Area of Science:

    • Neuroimaging
    • Biomarker Discovery
    • Neurology

    Background:

    • Multiple sclerosis (MS) monitoring relies on imaging biomarkers.
    • Resting-state functional MRI (rs-fMRI) provides functional insights complementing structural imaging.
    • Dynamic brain activity patterns may offer novel diagnostic and prognostic information in MS.

    Purpose of the Study:

    • To investigate a novel co-activation pattern (CAP) approach for dynamic rs-fMRI as a dual-purpose biomarker in MS.
    • To assess the diagnostic utility of dynamic CAP features for distinguishing MS patients from healthy controls (HCs).
    • To evaluate the correlation between dynamic CAP features and clinical disability (EDSS) in MS patients.

    Main Methods:

    • rs-fMRI data from 25 MS patients and 41 HCs were analyzed using a novel CAP-based dynamic approach.
    • Dynamic CAP features included dwell time, persistence, and transition probabilities.
    • LASSO regression was used for severity prediction, and performance was benchmarked against standard CAP and sliding-window (SW) methods.

    Main Results:

    • Significant differences in brain activity were found between MS patients and HCs within the default mode, sensorimotor, and language networks (p < 0.05).
    • Transition probabilities demonstrated strong correlations with EDSS (r > 0.75) and superior classification performance compared to standard CAP and SW approaches.
    • Network shifts, particularly transitions toward sensory, motor, and executive networks, correlated with disease severity and compensatory recruitment.

    Conclusions:

    • Dynamic brain activity patterns are altered in MS and are linked to clinical disability.
    • The proposed dynamic CAP approach enhances the distinction between MS patients and HCs, aiding clinical monitoring.
    • Transition probabilities show promise as a biomarker for tracking MS progression and understanding adaptive reorganization in response to disease severity.