Structure-function coupling reveals hemisphere-specific network reorganization after stroke

MRI is an excellent tool for monitoring functional and structural network reorganization after brain injury and may provide biomarkers for treatment stratification and novel neuromodulatory interventions. In ischemic stroke, functional network changes, particularly within the contralesional hemisphere, and structural integrity, most prominently of the corticospinal tract, have been successfully associated with behavioral deficit and outcome. However, these components are commonly studied separately and at single time points, which does not reflect the highly dynamic nature of brain network plasticity. Here, we characterized structural and functional connectivity (SC-FC) coupling in the healthy mouse brain and longitudinally assessed intra- and inter-hemispheric connections up to 4 weeks after cortical and cortico-striatal stroke. In the healthy brain, intra-hemispheric SC-FC coupling was lateralized in the sensorimotor network (SMN), whereas the default mode network (DMN) showed no significant hemispheric difference. Intra-hemispheric coupling exceeded inter-hemispheric coupling in the SMN. After cortical stroke, regions with high baseline intra-hemispheric SC-FC coupling remained largely stable, whereas initially weakly coupled sensorimotor regions showed delayed increases within the ischemic hemisphere. Contralesional intra-hemispheric SC-FC coupling changed little, but directional inter-hemispheric analyses revealed selective remodeling, including increased contralesional-to-ischemic coupling of primary motor cortex and reduced bidirectional coupling of medial sensorimotor cortex. Cortico-striatal stroke produced fewer longitudinal changes, dominated by reduced inter-hemispheric motor-cortex coupling. These alterations did not simply correspond to regional lesion involvement. Thus, hemisphere- and direction-resolved SC-FC coupling uncovers network- and stroke-model-specific reorganization not detectable when structural and functional connectivity are analyzed independently.