Closed-loop neuromodulation of spinal sensorimotor circuits controls refined locomotion after complete spinal cord injury

Abstract

Neuromodulation of spinal sensorimotor circuits improves motor control in animal models and humans with spinal cord injury. With common neuromodulation devices, electrical stimulation parameters are tuned manually and remain constant during movement. We developed a mechanistic framework to optimize neuromodulation in real time to achieve high-fidelity control of leg kinematics during locomotion in rats. We first uncovered relationships between neuromodulation parameters and recruitment of distinct sensorimotor circuits, resulting in predictive adjustments of leg kinematics. Second, we established a technological platform with embedded control policies that integrated robust movement feedback and feed-forward control loops in real time. These developments allowed us to conceive a neuroprosthetic system that controlled a broad range of foot trajectories during continuous locomotion in paralyzed rats. Animals with complete spinal cord injury performed more than 1000 successive steps without failure, and were able to climb staircases of various heights and lengths with precision and fluidity. Beyond therapeutic potential, these findings provide a conceptual and technical framework to personalize neuromodulation treatments for other neurological disorders.

Periodic modulation of repetitively elicited monosynaptic reflexes of the human lumbosacral spinal cord

“…Since the SCS-induced motor outputs are composed of series of stimulus-triggered PRM reflexes Minassian et al 2004), the stimulation frequency entrains the motoneuron firing rate and thus critically influences the muscle force produced. This relationship between the stimulation frequency and muscle force was also used in a recent study to achieve control of hindlimb kinematics during SCS-induced locomotion in paralyzed rats (Wenger et al 2014). The phenomenon described in the present report shows that, under specific conditions, the effective output frequencies (given by the larger-amplitude responses within the periodic modulation) may be lower than the stimulation frequency applied.…”

A Systematic Review of Experimental Strategies Aimed at Improving Motor Function after Acute and Chronic Spinal Cord Injury

“…There is recent promising evidence demonstrating recovery of stepping in rats with a transected spinal cord after a combinatorial approach incorporating locomotor training with electrical neuromodulation and a pharmacology agent. 10 There have not been many practical efforts in this direction in humans, however.…”

A Review of Neuromodulation in the Neurorehabilitation

“…SCI often leads to serious neurological sequelae and medical complications. Therefore, more efforts in medical practice development are needed to improve the quality of life of patients with SCI.It has been reported that SCS in lumbosacral segments helped restore voluntary control of locomotion in paralyzed rats after SCI [57].A study using closed-loop neuromodulation to treat rats with complete SCI found that it improved the locomotion and enabled animals to perform more than 1,000 successive steps without failure and to climb staircases of various heights and lengths with precision and fluidity [58]. Another similar study on rats, however, found no treatment effect [59].…”