Structural disconnectome analyses have provided valuable insights into how a stroke lesion results in widespread network disturbances and how these relate to deficits, recovery patterns, and outcomes. Previous analyses have primarily focused on patients with relatively mild to moderate deficits. However, outcomes vary among survivors of severe strokes, and the mechanisms of recovery remain poorly understood. This study assesses the association between lesion-induced network disconnection and outcome after severe stroke. Thirty-eight ischaemic stroke patients underwent MRI brain imaging early after stroke and longitudinal clinical follow-up. Lesion information was integrated with normative connectome data to infer individual disconnectome profiles on a localized regional and region-to-region pathway level. Ordinal logistic regressions were computed to link disconnectome information to the modified Rankin Scale after 3-6 months. Disconnections of ipsilesional frontal, parietal, and temporal cortical brain areas were significantly associated with a worse motor outcome after a severe stroke, adjusted for the initial deficit, lesion volume, and age. The analysis of the underlying pathways mediating this association revealed location-specific results: For frontal, prefrontal, and temporal brain areas, the association was primarily driven by relatively sparse intrahemispheric disconnections. In contrast, the ipsilesional primary motor cortex, the dorsal premotor cortex, and various parietal brain regions showed a remarkable involvement of either frontoparietal intrahemispheric or additionally interhemispheric disconnections. These results indicate that localized disconnection of multiple regions embedded in the structural frontoparietal network correlates with worse outcomes after severe stroke. Specifically, primary motor and parietal cortices might gain particular importance as they structurally link frontoparietal networks of both hemispheres. These data shed novel light on the significance of distinct brain networks for recovery after a severe stroke.
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