Cortical and Subcortical Effects of Transcutaneous Spinal Cord Stimulation in Humans with Tetraplegia

Abstract

An increasing number of studies supports the view that transcutaneous electrical stimulation of the spinal cord (TESS) promotes functional recovery in humans with spinal cord injury (SCI). However, the neural mechanisms contributing to these effects remain poorly understood. Here we examined motor-evoked potentials in arm muscles elicited by cortical and subcortical stimulation of corticospinal axons before and after 20 min of TESS (30 Hz pulses with a 5 kHz carrier frequency) and sham-TESS applied between C5 and C6 spinous processes in males and females with and without chronic incomplete cervical SCI. The amplitude of subcortical, but not cortical, motorevoked potentials increased in proximal and distal arm muscles for 75 min after TESS, but not sham-TESS, in control subjects and SCI participants, suggesting a subcortical origin for these effects. Intracortical inhibition, elicited by paired stimuli, increased after TESS in both groups. When TESS was applied without the 5 kHz carrier frequency both subcortical and cortical motor-evoked potentials were facilitated without changing intracortical inhibition, suggesting that the 5 kHz carrier frequency contributed to the cortical inhibitory effects. Hand and arm function improved largely when TESS was used with, compared with without, the 5 kHz carrier frequency. These novel observations demonstrate that TESS influences cortical and spinal networks, having an excitatory effect at the spinal level and an inhibitory effect at the cortical level. We hypothesized that these parallel effects contribute to further the recovery of limb function following SCI.

Transcutaneous Spinal Cord Stimulation Enhances Quadriceps Motor Evoked Potential in Healthy Participants: A Double-Blind Randomized Controlled Study

“…In our study, the increase in peak-to-peak Q and TA MEP amplitude was not maintained up to 2 and 4 min after tSCS. In contrast in a recent study a 20-min single session of tSCS increased the amplitude of subcortical motor evoked responses in arm muscles of people with a high level of SCI for up to 75 min [ 27 ]. Moreover, other studies have identified prolonged post intervention effects of tSCS based on improvement of spasticity [ 13 ] or the subjective perception of voluntary movement [ 8 ].…”

“…This is the first study to identify a selective effect of tSCS on Q MEPs compared to distal lower limb muscles such as the TA. Recently, an effect of non-invasive spinal stimulation applied at 30 Hz pulses, with a 5 kHz carrier frequency, has been identified on MEPs recorded from the upper limb muscles following TMS in cases of cervical spinal cord injury [ 27 ]. Previously low frequency stimulation of afferents has been shown to increase corticospinal excitability in the upper limb [ 42 ].…”

“…Activation of cutaneous afferents within the sural nerve have been shown to facilitate TMS evoked TA muscle activity [ 44 ]. Cutaneous afferents are also known to activate transcortical pathways as suggested in studies of people with dorsal column injury or corticospinal tract abnormalities [ 45 ], although activation of subcortical pathways may also be possible [ 27 , 46 ]. Cutaneous volleys evoke muscle responses at a transcortical latency followed by a longer-latency excitatory response [ 47 , 48 ] and ongoing voluntary contraction of lower limb muscles can also potentiate this longer-latency excitatory cutaneomuscular response [ 48 ].…”

“…However, these measurement tools have a low sensitivity to single session tSCS-induced neuromodulation and cannot detect small changes in neuromuscular activity. Neurophysiological methods aimed at measuring changes in spinal excitability, such as the PRM reflex and the Hoffman reflex, have been used to assess neuromodulation after tSCS [ 24 , 25 , 26 , 27 ]. However, the extent to which tSCS can lead to a change in cortical and spinal excitability has only been studied in the upper limb [ 27 ].…”

“…Neurophysiological methods aimed at measuring changes in spinal excitability, such as the PRM reflex and the Hoffman reflex, have been used to assess neuromodulation after tSCS [ 24 , 25 , 26 , 27 ]. However, the extent to which tSCS can lead to a change in cortical and spinal excitability has only been studied in the upper limb [ 27 ]. Therefore, the measurement of MEPs evoked by TMS has been used in this study as the standard and sensitive neurophysiological method to assess changes in excitability of the corticospinal pathway in response to tSCS.…”