Peripheral pathway rerouting shapes whole-brain functional network

Pathway rerouting is critical for severe peripheral nerve injury (PNI), which induces widespread neuroplastic alterations within the central nervous system, yet whether different rerouting approaches differentially affect whole-brain functional networks remains unknown. The present study investigated alterations in brain network organization following different peripheral pathway rerouting after PNI. Adult Sprague-Dawley rats underwent complete left brachial plexus transection and were assigned to nerve repair, end-to-end nerve transfer, end-to-side nerve transfer, or untreated PNI groups. Resting-state functional magnetic resonance imaging was acquired 7 months after surgery. Whole-brain functional connectivity matrices were constructed, and graph theoretical analysis was performed to assess global and nodal network properties, including global efficiency, nodal efficiency, and small-world characteristics. Rich-club, feeder, and local connections were further analyzed to characterize patterns of network reorganization. The results revealed significant differences in global efficiency, nodal efficiency, small-world organization and feeder connection among the four groups. Compared with the other reconstruction procedures, end-to-end nerve transfer showed reduced global efficiency, impaired small-world organization, lower nodal efficiency in subcortical regions, and increased functional connectivity and feeder connections, indicating reduced efficiency of large-scale information processing. In contrast, end-to-side nerve transfer preserved global efficiency, nodal efficiency, and small-world properties to a greater extent and was accompanied by more extensive increases in functional connectivity. These findings suggest that end-to-end nerve transfer appears to have a negative effect on the order of the whole-brain network, whereas end-to-side nerve transfer better preserves and restores network stability.