Peripheral nerve pathway reconnections promote the reorganization of central motor representations

Dexterous hand motor functions are highly flexible and finely controlled by complex neural commands from the motor cortex. However, in patients with brain injuries such as stroke, restoring fine motor control from the perilesional cortex remains extremely challenging. A major obstacle is the absence of appropriate non-human primate models to elucidate the behavioral and neural signatures of hand motor function during recovery following treatments. Here, we present a new non-human primate model that reflects the motor function recovery processes following lesion-induced hand paralysis after contralateral C7 nerve transfer (CC7) surgery, which establishes a new neural pathway from the ipsilateral cortex to control the paralyzed hand. By developing a hand reach-to-pinch task and quantifying finger kinematics, we established systematic, objective profiles of fine motor recovery in human patients and monkey models following CC7 treatment. Furthermore, when considering behavioral aspects, spontaneous recovery of hand motor skills was notably limited in human patients and monkey models, as indicated by the consistently abnormal "thumb-in-palm" patterns observed in finger kinematic analysis. However, the CC7 surgery gradually restored the finger kinematic patterns during hand-pinch actions to nearly identical patterns to those of the healthy hand. In addition, the human functional MRI and macaque electrophysiology results revealed, on a neural level, the emergence of a new command area and its spiking-based motor-command refinements specifically for the paralyzed hand in the contralesional M1 and premotor cortex (PMC) after CC7 treatment. Thus, our findings strongly support the notion that modifying peripheral nerve pathways greatly promotes the recovery of dexterous motor function in a paralyzed hand by reconstructing new motor-control neural mechanisms within the ipsilateral healthy motor cortex.