Dynamic Functional Connectivity Changes in Cortical and Cortico‐Striatal Strokes in Mice

AIMS: To determine how lesion size and location shape longitudinal functional connectivity (FC) changes after stroke. METHODS: Adult male mice underwent atlas-based resting-state fMRI at baseline and 1, 2, and 4 weeks after either a small photothrombotic cortical stroke (N = 25) or a larger transient cortico-striatal MCAO stroke (N = 6). FC was quantified across 98 atlas regions, focusing on sensorimotor cortex, striatum, and thalamus, including intra- and inter-hemispheric connectivity matrices and regional seed strength. RESULTS: Cortical stroke caused widespread hyperconnectivity at Weeks 1-2, with about 90% of connections increased, followed by partial normalization by Week 4. This effect declined most strongly in the ischemic hemisphere and remained more sustained contralesionally. In contrast, cortico-striatal stroke induced global hypoconnectivity at Week 1, with more than 90% of connections decreased, a modest and heterogeneous shift toward baseline at Week 2, and widespread decreases persisting at Week 4. A subset of sensorimotor connections showing opposite changes in the two models robustly separated groups at all post-stroke time points. Regional lesion involvement scaled with the magnitude of baseline-referenced FC alterations. CONCLUSION: Lesion topography drives distinct longitudinal FC trajectories after stroke and may help define network biomarkers and optimal windows for targeted interventions.