Date Published: March 7, 2019
Publisher: Public Library of Science
Author(s): Lynda M. Murray, Maria Knikou, Antal Nógrádi.
Targeted neuromodulation strategies that strengthen neuronal activity are in great need for restoring sensorimotor function after chronic spinal cord injury (SCI). In this study, we established changes in the motoneuron output of individuals with and without SCI after repeated noninvasive transspinal stimulation at rest over the thoracolumbar enlargement, the spinal location of leg motor circuits. Cases of motor incomplete and complete SCI were included to delineate potential differences when corticospinal motor drive is minimal. All 10 SCI and 10 healthy control subjects received daily monophasic transspinal stimuli of 1-ms duration at 0.2 Hz at right soleus transspinal evoked potential (TEP) subthreshold and suprathreshold intensities at rest. Before and two days after cessation of transspinal stimulation, we determined changes in TEP recruitment input-output curves, TEP amplitude at stimulation frequencies of 0.1, 0.125, 0.2, 0.33 and 1.0 Hz, and TEP postactivation depression upon transspinal paired stimuli at interstimulus intervals of 60, 100, 300, and 500 ms. TEPs were recorded at rest from bilateral ankle and knee flexor/extensor muscles. Repeated transspinal stimulation increased the motoneuron output over multiple segments. In control and complete SCI subjects, motoneuron output increased for knee muscles, while in motor incomplete SCI subjects motoneuron output increased for both ankle and knee muscles. In control subjects, TEPs homosynaptic and postactivation depression were present at baseline, and were potentiated for the distal ankle or knee flexor muscles. TEPs homosynaptic and postactivation depression at baseline depended on the completeness of the SCI, with minimal changes observed after transspinal stimulation. These results indicate that repeated transspinal stimulation increases spinal motoneuron responsiveness of ankle and knee muscles in the injured human spinal cord, and thus can promote motor recovery. This noninvasive neuromodulation method is a promising modality for promoting functional neuroplasticity after SCI.
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. Evidence supports for some recovery of standing and walking ability during or after epidural delivery of electrical current to the spinal cord of individuals with complete SCI that received concomitantly a variable number of locomotor training sessions [7–14]. Epidural stimulation also promoted bladder control, cardiovascular function, respiration and cough in human SCI [14–18]. Similarly, transcutaneous spinal cord (termed here transspinal) stimulation at low and high frequencies strengthens corticomotoneuronal connectivity, decreases hyperreflexia, improves bladder function, seated postural control, and autonomic cardiovascular function [19–23]. Step-like movements produced by transspinal stimulation , further support its ability to modulate spinal locomotor circuits in persons with paralysis. However, the effect of repeated low-frequency transspinal stimulation on the responsiveness of spinal motoneurons in individuals with SCI remains largely undetermined.
Neuromodulatory noninvasive therapeutic approaches that can strengthen motoneuron depolarization are in great need to promote recovery of motor function after SCI. Here we show for the first time that repeated low-frequency transspinal stimulation over the thoracolumbar enlargement, the location of leg motor circuits, increases the responsiveness of motoneurons over multiple segments in individuals with chronic motor incomplete and complete SCI. While transspinal stimulation induced mixed effects on homosynaptic and postactivation TEP depression, this intervention may be used to functionally improve the neural control of standing and walking.
This study provides evidence that repeated transspinal stimulation increases the responsiveness of motoneuron pools over multiple spinal segments, and produces mixed effects in spinal inhibitory mechanisms after motor paralysis or paresis. From a functional perspective, increased motoneuron output may contribute to better motor control and improved tasks such as standing and walking. We propose that noninvasive low-frequency transspinal stimulation can be used to strengthen spinal synapses and depolarization of alpha motoneurons in individuals with chronic motor paralysis or paresis.