Abstract

Rehabilitative interventions involving electrical stimulation show promise for neuroplastic recovery in people living with Spinal Cord Injury (SCI). However, the understanding of how stimulation interacts with descending and spinal excitability remain unclear. In this study we compared the immediate and short-term (within a few minutes) effects of pairing Transcranial Magnetic Stimulation (TMS) with transcutaneous Spinal Cord stimulation (tSCS) and Peripheral Nerve Stimulation (PNS) on Corticospinal excitability in healthy subjects. Three separate experimental conditions were assessed. In Experiment I, paired associative stimulation (PAS) was applied, involving repeated pairing of single pulses of TMS and tSCS, either arriving simultaneously at the spinal motoneurones (PAS0ms) or slightly delayed (PAS5ms). Corticospinal and spinal excitability, and motor performance, were assessed before and after the PAS interventions in 24 subjects. Experiment II compared the immediate effects of tSCS and PNS on corticospinal excitability in 20 subjects. Experiment III compared the immediate effects of tSCS with tSCS delivered at the same stimulation amplitude but modulated with a carrier frequency (in the kHz range) on corticospinal excitability in 10 subjects. Electromyography (EMG) electrodes were placed over the Tibialis Anterior (TA) soleus (SOL) and vastus medialis (VM) muscles and stimulation electrodes (cathodes) were placed on the lumbar spine (tSCS) and lateral to the popliteal fossa (PNS). TMS over the primary motor cortex (M1) was paired with tSCS or PNS to produce Motor Evoked Potentials (MEPs) in the TA and SOL muscles. Simultaneous delivery of repetitive PAS (PAS0ms) increased corticospinal excitability and H-reflex amplitude at least 5 min after the intervention, and dorsiflexion force was increased in a force-matching task. When comparing effects on descending excitability between tSCS and PNS, a subsequent facilitation in MEPs was observed following tSCS at 30-50 ms which was not present following PNS. To a lesser extent this facilitatory effect was also observed with HF- tSCS at subthreshold currents. Here we have shown that repeated pairing of TMS and tSCS can increase corticospinal excitability when timed to arrive simultaneously at the alpha-motoneurone and can influence functional motor output. These results may be useful in optimizing stimulation parameters for neuroplasticity in people living with SCI.

Highlights

  • Non-invasive electrical stimulation (ES) is commonly used alongside activity-based rehabilitation to improve or recover motor function in people with Spinal Cord Injury (SCI)

  • Dorsiflexion EMG in a force matching task was unaffected by PAS interval (p > 0.05; n = 11), dorsiflexion force increased after PAS0ms (n = 11; p < 0.01), and Foot/Hand ratio tended to increase ( this did not reach statistical significance (n = 11; p = 0.11)), hinting that foot force increased relative to hand force for PAS0ms but not PAS5ms

  • We report that trains of tSCS increased corticospinal excitability, whereas trains of peripheral nerve stimulation (PNS) did not, which may explain the immediate recovery of voluntary control, which has been observed in people with chronic SCI when SCS is switched on

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Summary

Introduction

Non-invasive electrical stimulation (ES) is commonly used alongside activity-based rehabilitation to improve or recover motor function in people with Spinal Cord Injury (SCI). Recent studies have shown that non-invasive ES applied over the thoracolumbar cord (transcutaneous spinal cord stimulation tSCS) enabled immediate restoration of some voluntary movement in people with complete and incomplete SCI (Gerasimenko et al, 2015a; Hofstoetter et al, 2015). These effects appear to improve over several weeks or months of tSCS combined with volitional movement (Gerasimenko et al, 2015a; Sayenko et al, 2019). Short-term effects could be due to spike-timing dependent plasticity (STDP) like mechanisms, where repeated pairing of descending and ascending input cause strengthening of synaptic connections in the cord (cortico-motoneuronal and/or Iaafferent-α-motoneuron) (Nishimura et al, 2013)

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