Spinal cord bioelectronic interfaces: opportunities in neural recording and clinical challenges

Abstract

Bioelectronic stimulation of the spinal cord has demonstrated significant progress in restoration of motor function in spinal cord injury (SCI). The proximal, uninjured spinal cord presents a viable target for the recording and generation of control signals to drive targeted stimulation. Signals have been directly recorded from the spinal cord in behaving animals and correlated with limb kinematics. Advances in flexible materials, electrode impedance and signal analysis will allow SCR to be used in next-generation neuroprosthetics. In this review, we summarize the technological advances enabling progress in SCR and describe systematically the clinical challenges facing spinal cord bioelectronic interfaces and potential solutions, from device manufacture, surgical implantation to chronic effects of foreign body reaction and stress-strain mismatches between electrodes and neural tissue. Finally, we establish our vision of bi-directional closed-loop spinal cord bioelectronic bypass interfaces that enable the communication of disrupted sensory signals and restoration of motor function in SCI.

Flexible Circumferential Bioelectronics to Enable 360-degree Recording and Stimulation of the Spinal Cord

“…The density of electrode recordings around the spinal cord also allows better differentiation of various hotspots around the spinal cord. The descending motor pathway is mediated by the rubrospinal and corticospinal tract in rats [1], [20], [21]This is substantiated by the spinal cord topography maps generated in Fig. 3C, where two locations of peak activation are highlighted simultaneously following MEP stimulation; this would correspond to the approximate location of these descending motor axons.…”

“…Conversely, the capacity to effectively interface with the spinal cord presents a unique opportunity to unlock unprecedented potential in modulating and potentially restoring these crucial functions. This capability could dramatically alter the landscape of therapeutic interventions for spinal cord injuries and associated neurological disorders [1]. Recent advances in targeted spinal cord stimulation (SCS) have enabled the restoration of assisted walking in patients paralyzed by spinal cord injury (SCI) [2]- [4].…”

Flexible circumferential bioelectronics to enable 360-degree recording and stimulation of the spinal cord

“…The density of electrode recordings around the spinal cord also allows better differentiation of various hotspots around the spinal cord. The descending motor pathway is mediated by the rubrospinal and corticospinal tract in rats ( 1 , 23 , 24 ). This is substantiated by the spinal cord topography maps generated in Fig.…”

“…Conversely, the capacity to effectively interface with the spinal cord presents a unique opportunity to unlock unprecedented potential in modulating and potentially restoring these crucial functions. This capability could markedly alter the landscape of therapeutic interventions for spinal cord injuries and associated neurological disorders (1). Recent advances in targeted spinal cord stimulation (SCS) have enabled the restoration of assisted walking in patients paralyzed by spinal cord injury (SCI) (2)(3)(4).…”

Ultraflexible electrodes for recording neural activity in the mouse spinal cord during motor behavior

“…Because most electrodes are substantially more rigid than nervous tissue, they typically fail to stay compliant with the spinal cord during such motions, resulting in excessive noise, position drifts, injury to the tissue, and quick deterioration in recording performance. 17 – 20 As a result, electrophysiological recordings in the spinal cord are mostly restricted to ex vivo , 21 , 22 anesthetized, 23 – 26 or acute preparations. 27 Even in the impressive but few examples of spinal recordings in awake-behaving contexts, animals were highly constrained, 28 – 33 motor activity was tightly circumscribed (e.g., isometric contractions of wrist muscles), 28 , 29 , 31 , 32 and/or neurons were recorded one at a time 30 , 34 , 35 or for short time periods.…”