Sub-threshold spinal cord stimulation facilitates spontaneous motor activity in spinal rats

Abstract

BackgroundEpidural stimulation of the spinal cord can be used to enable stepping on a treadmill (electrical enabling motor control, eEmc) after a complete mid-thoracic spinal cord transection in adult rats. Herein we have studied the effects of eEmc using a sub-threshold intensity of stimulation combined with spontaneous load-bearing proprioception to facilitate hindlimb stepping and standing during daily cage activity in paralyzed rats.MethodsWe hypothesized that eEmc combined with spontaneous cage activity would greatly increase the frequency and level of activation of the locomotor circuits in paralyzed rats. Spontaneous cage activity was recorded using a specially designed swivel connector to record EMG signals and an IR based camcorder to record video.Results and conclusionThe spinal rats initially were very lethargic in their cages showing little movement. Without eEmc, the rats remained rather inactive with the torso rarely being elevated from the cage floor. When the rats used their forelimbs to move, the hindlimbs were extended and dragged behind with little or no flexion. In contrast, with eEmc the rats were highly active and the hindlimbs showed robust alternating flexion and extension resulting in step-like movements during forelimb-facilitated locomotion and often would stand using the sides of the cages as support. The mean and summed integrated EMG levels in both a hindlimb flexor and extensor muscle were higher with than without eEmc. These data suggest that eEmc, in combination with the associated proprioceptive input, can modulate the spinal networks to significantly amplify the amount and robustness of spontaneous motor activity in paralyzed rats.

Noninvasive Reactivation of Motor Descending Control after Paralysis

“…For example, at stimulation intensities 20% below the motor threshold the spinal networks in paralyzed rats were modulated to a physiological state that enabled proprioception and cutaneous input to initiate a fivefold increase in spontaneous cage activity and more normal EMG bursting patterns. 26 We propose an elemental spinal network that could generate the observed output patterns with pharmacological and electrical spinal cord stimulation in the presence of proprioceptive input in our paralyzed subjects. Such a pathway architecture can conceptually account for all interactive observations made in the present study when guided by activity-dependent mechanisms (i.e., stimulation, pharmacology, conditioning, and training).…”

Trans-spinal direct current stimulation for the modulation of the lumbar spinal motor networks

“…One possible source of variation shown by others [20,21,45], are the different polymorphisms of BDNF due to its involvement in neuroplasticity and synapse function [46][47][48]. However, our analysis does not show such a clear dependency for the data presented here.…”

“…For instance, in a study by Gerasimenko and colleagues, several subjects diagnosed with motor complete paralysis were able to partly regain voluntary movement control after an 18-week training program, including weekly transcutaneous pulsed, supra-threshold spinal stimulation in combination with pharmaceutical intervention. Thus, while the more substantial improvements in voluntary control have only been achieved after long periods of combined manual training and electrical stimulation [36][37][38][46][47][48][49], immediate acute effects can already be observed during the first application [47,50].…”

“…Both axons were modeled as simple cylinders with a length of 40 mm and a diameter of 10 µm. Reported diameters for both axon types, including myelin, are within a range of 13 µm to 20 µm for afferent (Ia) fibers [46] and 16 µm to 20 µm for efferent axons originating from cortical Betz neurons [47,48]. The inner axonal diameter, without myelin, was estimated via multiplication of the g-ratio (g=0.6) [49], whereby the chosen axon diameter of 10 µm is within the resulting range for both axons.…”

“…Using both invasive [36,37,46,47] and noninvasive [38,48] approaches, as well as either sub- [38,46,48] and supra-threshold [38,47] pulsed stimulation, a variety of studies have reported significant long or short-term improvements on voluntary motor control, weight bearing or other clinical outcome parameters [36][37][38][46][47][48][49]. For instance, in a study by Gerasimenko and colleagues, several subjects diagnosed with motor complete paralysis were able to partly regain voluntary movement control after an 18-week training program, including weekly transcutaneous pulsed, supra-threshold spinal stimulation in combination with pharmaceutical intervention.…”