Early premotor-somatosensory remodeling after primary motor cortex injury.

Focal ischemic injury to the primary motor cortex (M1) disrupts distributed sensorimotor networks and initiates structural remodeling in spared cortical regions. Although previous studies have demonstrated axonal sprouting from ventral premotor cortex (PMv) to somatosensory area 1/2 at later post-injury time points, the onset of this reorganization remains unknown. We examined whether PMv-to-area 1/2 structural remodeling is detectable four weeks after focal infarction of the M1 distal forelimb representation in adult squirrel monkeys. Animals received focal ischemic lesions of the M1 distal forelimb area followed by anterograde tracer injections into the PMv distal forelimb representation. Putative synaptic boutons in area 1/2 were quantified using unbiased stereology and compared with intact controls. Four weeks after injury, bouton density within area 1/2 was significantly greater in lesion animals than in controls, indicating robust early remodeling of PMv-to-area 1/2 projections. Behavioral assessments showed partial recovery of skilled forelimb function over the same period. These findings demonstrate that corticocortical structural remodeling begins within the first month after focal M1 injury, identifying an early post-stroke window during which reorganization of premotor-somatosensory pathways may support the restoration of sensorimotor function. Significance statementRecovery after motor cortex injury depends on reorganization of spared neural circuits, but the timing of these changes remains poorly understood. Using a nonhuman primate model of focal motor cortex injury, we show that projections from ventral premotor cortex to higher-order somatosensory area 1/2 undergo substantial structural remodeling within four weeks of injury. Unbiased stereological analysis revealed a near doubling of axonal boutons in this pathway during a period of spontaneous behavioral recovery. These findings demonstrate that cortical network remodeling begins much earlier than previously recognized and identify an early post-injury window during which spared sensorimotor circuits may be particularly amenable to therapeutic intervention.