Probing the Human Spinal Locomotor Circuits by Phasic Step-Induced Feedback and by Tonic Electrical and Pharmacological Neuromodulation

Abstract

The mammalian lumbar spinal cord experimentally isolated from supraspinal and afferent feedback input remains capable of expressing some basic locomotor function when appropriately stimulated. This ability has been attributed to spinal neural circuits referred to as central pattern generators (CPGs). In individuals with a severe spinal cord injury, rhythmic activity in paralyzed leg muscles can be generated by phasic proprioceptive feedback during therapist- or robotic-assisted stepping on a motorized treadmill. Here, we critically review to what extent the resulting motor output represents locomotor-like activity, and whether these motor patterns are the result of activation of CPGs, as commonly suggested in the literature. Attempts will be made to further delineate the pivotal roles played by mechanisms such as spinal proprioceptive reflexes and their alterations after spinal cord injury, the central excitability level, and by neurotransmitters critical for spinal locomotor activity. We will discuss the view that the muscle activity produced during assisted passive treadmill stepping is resulting from the entrainment of spinal reflex circuits by the cyclically generated proprioceptive feedback. We suggest that the activation of CPG circuits depends rather on the presence of a sustained tonic excitatory drive, as can be provided by electrical spinal cord stimulation, or by specific combinations of dopaminergic agonists, adrenergic/ dopaminergic precursors and/or 5-HT receptor agonists. Novel rehabilitation strategies using spinal cord stimulation and rhythmic-activity producing drugs during locomotor therapy will pave the way for clinically relevant advances in restoration of motor function in people with severe spinal cord injury.

Spinal Control of Locomotion: Individual Neurons, Their Circuits and Functions

“…Despite an abundance of evidence on gait recovery by locomotor training in people with spinal cord injury ( Smith and Knikou, 2016 ), the neurophysiological changes with respect to function and interaction of PINs, CINs, and IaINs-IbINs remain poorly understood. In addition, repetitive stimulation of the brain and/or spinal cord ( Knikou, 2014 ; Hofstoetter et al, 2017 ) can be utilized alone or combined with activity-based therapies to further promote locomotor function recovery in people with pathological gait; however, stimulation protocols are still in their infancy and warrant further investigation since they cannot target a specific neuromodulation pathway.…”

Transspinal stimulation increases motoneuron output of multiple segments in human spinal cord injury

“…Targeted neuromodulation strategies that strengthen neuronal activity are in great need for restoring sensorimotor function after chronic spinal cord injury (SCI). Within this concept, several therapeutic approaches promoting neuromodulation and thereby neuroplasticity have been adapted over the last few decades [1–6]. One of these methods includes spinal cord stimulation delivered epidurally or transcutaneously to the lumbar spinal region, the location of the leg motor circuits.…”

Repeated transspinal stimulation decreases soleus H-reflex excitability and restores spinal inhibition in human spinal cord injury

“…Electrical stimulation is commonly used to promote recovery of motor function in upper motoneuron lesions. Stimulation of the primary motor cortex, spinal cord, peripheral nerve(s), and muscle(s) has been employed to improve sensorimotor function after spinal cord injury (SCI) [1–6]. Transcutaneous spinal cord (termed here transspinal) stimulation delivered via single monophasic pulses generates transspinal evoked potentials (TEPs) simultaneously in both legs of individuals with and without SCI that have distinct characteristics regarding their latency, duration, shape, and spinal integration [7–10].…”