Central Pattern Generators in Spinal Cord Injury: Mechanisms, Modulation, and Therapeutic Strategies for Motor Recovery.

Abstract

Spinal cord injury (SCI) compromises the communication between the brain and spinal circuits involved in locomotion, resulting in severe motor dysfunction. However, currently available therapies have limited effectiveness in restoring motor function after SCI. Recent research has highlighted the importance of the central pattern generator (CPG), a spinal circuitry responsible for generating coordinated patterns of leg motor activity in the absence of brain-derived inputs, in locomotor recovery. Therefore, a highly promising approach for restorative treatment after SCI involves reactivating the CPG network to harness its rhythmic activity-generating capabilities. Various forms of neuromodulation, such as pharmacological agents, electrical stimulation, and light-based regulatory strategies, have been utilized for this purpose. This review summarizes the organizational structure and functional characteristics of CPG networks, examines CPG alterations following SCI, and evaluates recent advances in neuromodulation strategies aimed at restoring motor function through CPG reactivation. This review also highlights existing challenges and outlines prospective directions for future research in the field.