Mechanisms Underlying the Neuromodulation of Spinal Circuits for Correcting Gait and Balance Deficits after Spinal Cord Injury

• Simulations reproduce motor pattern formation during epidural electrical stimulation
• Epidural electrical stimulation modulates muscle spindle feedback circuits
• Simulations lead to novel stimulation protocols correcting gait and balance deficits
• This new conceptual framework improves stimulation protocols for clinical applications

SummaryEpidural electrical stimulation of lumbar segments facilitates standing and walking in animal models and humans with spinal cord injury. However, the mechanisms through which this neuromodulation therapy engages spinal circuits remain enigmatic. Using computer simulations and behavioral experiments, we provide evidence that epidural electrical stimulation interacts with muscle spindle feedback circuits to modulate muscle activity during locomotion. Hypothesis-driven strategies emerging from simulations steered the design of stimulation protocols that adjust bilateral hindlimb kinematics throughout gait execution. These stimulation strategies corrected subject-specific gait and balance deficits in rats with incomplete and complete spinal cord injury. The conservation of muscle spindle feedback circuits across mammals suggests that the same mechanisms may facilitate motor control in humans. These results provide a conceptual framework to improve stimulation protocols for clinical applications.