Functional vulnerability of the M1/S1 transitional zone in post-stroke motor deficits in mice

Functional outcome after cortical infarction depends not only on lesion volume but also on its anatomical location. However, the functional differences between the primary motor cortex (M1), secondary motor cortex (M2), and primary somatosensory cortex (S1) have rarely been compared within a single task, and the functional significance of the territory between them remains unexplored. In this study, we induced photothrombotic infarctions centered on M1, M2, or S1 in mice and assessed right forelimb movement during a skilled lever-pull task for up to 28 days post-infarction, using DeepLabCut with manual curation. By registering every lesion to the Allen Mouse Brain Common Coordinate Framework, we performed pixel-wise mapping of impairment independent of anatomical boundaries. We found that while lesion volume in M1 correlated with the magnitude of the deficit, M2 lesions failed to induce detectable deficits, and S1-centered lesions produced deficits that did not persist above baseline. Importantly, pixel-wise mapping revealed that infarcts encompassing the M1/S1 transitional zone caused the most severe and persistent deficits. These results demonstrate that coverage of this motor-somatosensory transitional zone, rather than anatomical labeling, is the key determinant of behavioral impairment and its long-term recovery.