Spinal Cord Stimulation to Enable Leg Motor Control and Walking in People with Spinal Cord Injury

Abstract

Spinal cord injury (SCI) disrupts the communication between the brain and the spinal circuits that control movement and integrate sensory feedback, which are usually located below the lesion. The disruption of the different anatomical sources of descending motor control and ascending sensory afferents can result in complete or partial, but permanent motor paralysis. For decades, recovery of motor function after long-standing SCI was thought impossible because of the severe and multi-modal failure of these bidirectional communication pathways. This conclusion was supported by overwhelming and disappointing empirical evidence showing poor recovery in people with chronic (>6 months post-injury), severe SCI despite intensive rehabilitation. However, a recent wave of clinical studies has reported unprecedented outcomes in people with both incomplete and complete SCI, independently demonstrating the long-term recovery of voluntary motor function in the chronic stage after SCI. These studies utilized a combination of intensive rehabilitation and electrical spinal cord stimulation (SCS), which was delivered via epidural multi-electrode arrays implanted between the vertebral bone and the dura mater of the lumbosacral spinal cord. SCS has a long history of applications in motor control, which started soon after its first applications as interventional studies in pain management. To date, SCS has been applied in thousands of individuals with neuromotor disorders ranging from multiple sclerosis to SCI. However, even though the motor-enabling effects of SCS were first observed about half a century ago, the lack of a coherent conceptual framework to interpret and expand these clinical findings hindered the evolution of this technology into a clinical therapy. More importantly, it led to substantial variability in the clinical reports ranging from anecdotal to subjective descriptions of motor improvements, without standardized methods and rigorous statistical analyses. For several decades, these limitations clouded the potential of SCS to promote long-term recovery in individuals with SCI. In this chapter, we present the historical background for the development of SCS to treat motor disorders and its evolution toward current applications for neurorehabilitation in individuals with SCI (Sect. 18.1). We then provide an overview of the conjectured mechanisms of action (Sect. 18.2), and how this collective knowledge has been used to develop SCS into a promising approach to treat motor paralysis after SCI, ranging from tonic stimulation to more sophisticated spatiotemporal protocols (Sect. 18.3). Finally, we open up this review to the recent development of non-invasive methods to deliver SCS, namely transcutaneous SCS, and its comparison with epidural SCS in terms of functional effects and underlying mechanisms (Sect. 18.4).

Fundamental Limitations of Kilohertz-Frequency Carriers in Afferent Fiber Recruitment With Transcutaneous Spinal Cord Stimulation

“…Decades of research in computational modeling 6,11,12 and neurophysiological studies in animals 13,14 and humans 15,16 support the notion that the motor effects evoked by epidural spinal cord stimulation (eSCS) are elicited by artificially induced action potentials in medium to largediameter somatosensory fibers within the posterior roots 17,18 . Therefore, the activity of specific neural networks within the spinal cord can be effectively modulated by electrical stimulation of their afferents-a fundamental aspect of neuromodulation 19 .…”

“…Recruitment of afferent fibers by neurostimulation is an essential component for neuromodulation 24 . Studies in computational modeling and human neurophysiology have suggested that muscle responses elicited with conventional waveforms by eSCS and tSCS of the lumbar spinal cord are mediated by the preferential recruitment of proprioceptive fibers within the posterior roots 17,18 . However, the activation mechanisms of KHF waveforms in tSCS remain poorly understood.…”

“…However, the specific neural substrates targeted by these novel techniques and the mechanisms by which they are activated remain largely understudied. In the present study, we use human neurophysiology and computational modeling to explore these fundamental questions on two common stimulation waveforms currently employed in transcutaneous spinal cord stimulation (tSCS).Decades of research in computational modeling 6,11,12 and neurophysiological studies in animals 13,14 and humans 15,16 support the notion that the motor effects evoked by epidural spinal cord stimulation (eSCS) are elicited by artificially induced action potentials in medium to largediameter somatosensory fibers within the posterior roots 17,18 . Therefore, the activity of specific neural networks within the spinal cord can be effectively modulated by electrical stimulation of their afferents-a fundamental aspect of neuromodulation 19 .…”

Enhanced selectivity of transcutaneous spinal cord stimulation by multielectrode configuration

“…However, because of the complex topographic anatomy in the lumbosacral spinal cord (Wall et al, 1990), noninvasive stimulation at different lumbosacral vertebral segments can excite both afferent and efferent pathways to different degrees. The engagement of each pathway is crucial to both the immediate prosthetic effect that may be enabled by tSCS and the rehabilitation effect that may be observed through SCS-assisted therapy (Seáñez et al, 2022). Therefore, careful evaluation of evoked responses should be performed.…”