Recruitment of upper-limb motoneurons with epidural electrical stimulation of the cervical spinal cord

Nathan Greiner,Sara Conti,Simon Borgognon,Henri Lorach,Marco Capogrosso,Nicholas James,Melanie Kaeser,Jocelyne Bloch,Giuseppe Schiavone,Grégoire Courtine,Stéphanie Lacour,Florian Fallegger,Beatrice Barra

doi:10.1038/s41467-020-20703-1

Abstract

Epidural electrical stimulation (EES) of lumbosacral sensorimotor circuits improves leg motor control in animals and humans with spinal cord injury (SCI). Upper-limb motor control involves similar circuits, located in the cervical spinal cord, suggesting that EES could also improve arm and hand movements after quadriplegia. However, the ability of cervical EES to selectively modulate specific upper-limb motor nuclei remains unclear. Here, we combined a computational model of the cervical spinal cord with experiments in macaque monkeys to explore the mechanisms of upper-limb motoneuron recruitment with EES and characterize the selectivity of cervical interfaces. We show that lateral electrodes produce a segmental recruitment of arm motoneurons mediated by the direct activation of sensory afferents, and that muscle responses to EES are modulated during movement. Intraoperative recordings suggested similar properties in humans at rest. These modelling and experimental results can be applied for the development of neurotechnologies designed for the improvement of arm and hand control in humans with quadriplegia.

Highlights

Epidural electrical stimulation (EES) of lumbosacral sensorimotor circuits improves leg motor control in animals and humans with spinal cord injury (SCI)
Electrophysiological experiments in monkeys and humans revealed that: (a) cervical EES recruits upper-limb motoneurons transsynaptically; (b) lateral electrodes engage upper-limb motor nuclei with a rostro-caudal order that reflects their segmental innervation in the cervical spinal cord; and (c) the modulation of upper-limb muscle activity exerted by EES in behaving monkeys is movement-phase dependent
Keeping constant the mean number of synapses per Iamotoneuron pair, we found that the number of Iaafferents that needs to be recruited to excite a given motor nucleus is determined by the product rconnec × gsyn (Fig. 6b)

Summary

Introduction

Epidural electrical stimulation (EES) of lumbosacral sensorimotor circuits improves leg motor control in animals and humans with spinal cord injury (SCI). Computational and experimental studies conducted in animal models and humans[10,11,12,13,14,15,16] have brought evidence that EES applied over the lumbosacral spinal cord primarily engages large myelinated afferent fibers running in the dorsal roots and dorsal columns of the spinal cord These fibers form synaptic connections with lumbosacral spinal interneurons and motoneurons, thereby constituting a gateway to the motor circuits controlling leg muscles[17,18]. We investigated the mechanisms underlying the recruitment of arm and hand motoneurons with EES of the cervical spinal cord and we inferred the properties that epidural implants should have to direct the modulation exerted by EES toward specific upper-limb motor nuclei To this end, we implemented a detailed computational model capable of estimating the recruitment of various populations of cervical nerve fibers and neurons in response to single pulses of EES. Electrophysiological experiments in monkeys and humans revealed that: (a) cervical EES recruits upper-limb motoneurons transsynaptically; (b) lateral electrodes engage upper-limb motor nuclei with a rostro-caudal order that reflects their segmental innervation in the cervical spinal cord; and (c) the modulation of upper-limb muscle activity exerted by EES in behaving monkeys is movement-phase dependent

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Discussion

Conclusion