Structural reserve-dependent cortical rerouting of motor control after stroke.

Structural cortico-cortical connectivity is essential for motor recovery after stroke, with undamaged fibre tracts potentially serving as structural reserve for functional reorganization. Yet, the mechanisms by which the structural reserve contributes to changes in functional network configurations to improve post-stroke motor control remain unknown. Here, we assessed structural (diffusion spectrum imaging) and effective (functional MRI-based dynamic causal modelling) connectivity to examine how the structural reserve may guide motor network reorganization of upper limb motor control. Specific features of cortico-cortical structural reserve were associated with distinct patterns of functional network configurations: limited intrahemispheric structural reserve between ipsilesional primary motor cortex and premotor areas was linked to interhemispheric rerouting of motor commands via the contralesional primary motor cortex, particularly when ipsilesional corticospinal tract integrity was low. In contrast, limited interhemispheric structural reserve between ipsilesional primary motor cortex and contralesional premotor areas was related to intrahemispheric rerouting via the ipsilesional premotor cortex, especially in patients with high residual corticospinal tract integrity. Even though both alternative pathways may allow bypassing damaged corticospinal tract fibres originating from the ipsilesional primary motor cortex, we observed a clear behavioural dissociation: in patients who substantially recovered, enhanced intrahemispheric rerouting was indicative of better hand function, reflecting beneficial reorganization. Conversely, interhemispheric rerouting was associated with pronounced motor impairment of the paretic arm and primarily observed in non-substantially recovered patients, in line with task-specific maladaptive reorganization. Our findings emphasize that the motor network's available structural reserve critically shapes functional network reorganization by predetermining whether motor commands are primarily rerouted intra- or interhemispherically with distinct implications for motor recovery. Besides helping to reconcile previous conflicting interpretations on the role of contralesional primary motor cortex, our results underscore that the individual level of structural motor network reserve should be considered for future therapeutic approaches aiming at amplifying motor recovery after stroke.