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bioRxivNeurosciencePreprint

Individual connectome fingerprints reveal early stabilization and long-term circuit remodeling after stroke

Andrea SantoroiD, Alessandro Lucatelli, Fabienne WindeliD, Beatrice LugliiD, Maria Giulia PretiiD, Lisa FleuryiD, Flavia PetrusoiD, Elena BeanatoiD, Dimitri Van De VilleiD, Friedhelm Christoph HummeliD, Enrico AmicoiD

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Abstract

Stroke is one of the leading causes of global disability, yet the principles governing how focal brain injury disrupts large-scale neural connectivity over time remain poorly understood. Here, we leverage a longitudinal multimodal dataset to track the evolution of individual-specific connectivity patterns, or brain fingerprints, over the first year after stroke. Despite a persistent shift from healthy architecture, we demonstrate that each patients unique functional connectome fingerprint is remarkably resilient and stabilizes within three weeks. This early global stabilization masks a protracted system-specific reorganization of brain circuits, which is characterized by an initial increase in connectivity within sensory and attention systems, followed by a decline across higher-level association networks. A joint structure-function embedding further shows that recovery involves a gradual shift toward the normative healthy range, driven primarily by functional reconfiguration atop a stable structural lesion. Crucially, a multivariate prediction model reveals that early functional signatures selectively forecast long-term impairment in language, executive function, and attention. Together, our results define the post-stroke brain as a shifting but constrained dynamical system, identifying early-stabilized brain patterns as biomarkers for individual recovery profiles and targets for personalized neurorehabilitation.

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