Paired Stimulation of Human Motor Cortex and Cervical Spine Generates Synergistic Motor Responses

Introduction: By electrically stimulating the brain and spinal cord, it is possible to reinforce sensorimotor pathways and improve skilled movement in people with neurological impairments. While most existing paired stimulation protocols target either the motor system or cortical sensorimotor connections, we developed a technique in rats timed for convergence of descending motor and spinal afferent connections in the cervical cord. Here we test this technique in humans and hypothesize that brain stimulation over motor cortex combined with posterior cervical spinal cord stimulation would lead to synergistic upper extremity muscle responses, contingent on the precise timing of stimulation.

Methods: We tested this idea during clinically indicated spine surgeries that allowed access to the spinal epidural space. Motor cortex was stimulated intraoperatively through scalp electrodes, while the spinal cord was stimulated through epidural electrodes placed either anteriorly or posteriorly, depending on surgical approach. We adjusted the inter-stimulus interval between motor cortex and spinal cord stimulation while motor evoked potentials (MEPs) were recorded in multiple arm and leg muscles.

Results: When transcranial electrical stimulation was paired with posterior (n = 47, 27M/20F), but not anterior (n = 13, 5M/8F), epidural spinal cord stimulation, MEPs were augmented over 500% compared to brain stimulation alone. The enhancement was only present when stimuli from the descending motor pathway and the spinal afferents converged in the cervical spinal cord. Strong effects of paired stimulation were observed above, at, and below segments with myelopathy. Paired stimulation also increased muscle selectivity of MEPs when compared to isolated brain-only or spinal only stimulation.

Conclusion : The demonstrated MEP facilitation from pairing brain and spinal stimulation is a prerequisite for the next goal of inducing timing-dependent plasticity. The large effect size of this invasive pairing technique and the robustness of the pairing effects in spinal cord injury make it a promising candidate for therapeutic neuromodulation.