Brain network dynamics reflect psychiatric illness status and transdiagnostic symptom profiles across health and disease.

Cocuzza, Carrisa V; Chopra, Sidhant; Segal, Ashlea; Labache, Loïc; Chin, Rowena; Joss, Kaley; Holmes, Avram J · Nat Commun · 2026

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Abstract

The network organization of the human brain dynamically reconfigures in response to changing environmental demands, an adaptive process that may be disrupted in a symptom-relevant manner across psychiatric illnesses. Here, in a transdiagnostic sample of participants with (n = 134) and without (n = 85) psychiatric diagnoses, functional connectomes from intrinsic (resting-state) and task-evoked fMRI were decomposed to identify constraints on brain network dynamics across six cognitive states. Hierarchical clustering of 110 clinical, behavioral, and cognitive measures identified participant-specific symptom profiles, revealing four core dimensions of functioning: internalizing, externalizing, cognitive, and social/reward. Brain network dynamics were flattened across cognitive states in individuals with psychiatric illness and could be used to accurately separate dimensional symptom profiles more robustly than both case/control status and primary diagnostic grouping. A key role of inhibitory cognitive control and frontoparietal network interactions was uncovered through systematic model comparison. We provide evidence that brain network dynamics can accurately differentiate the extent that psychiatrically-relevant dimensions of functioning are exhibited across health and disease.

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