The Immediate and Short-Term Effects of Transcutaneous Spinal Cord Stimulation and Peripheral Nerve Stimulation on Corticospinal Excitability

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 (PAS_0ms) or slightly delayed (PAS_5ms). 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 (PAS_0ms) 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.

Keywords: corticospinal excitability; paired associative stimulation (PAS); peripheral nerve stimulation (PNS); rehabilitation; spinal cord stimulation (SCS); transcranial magnetic stimulation.

FIGURE 1

Schematic representation of Experiment I setup. Transcutaneous stimulating electrodes were placed paravertebral at landmarks over T12/L1 to L3/4 spinous processes (tSCS) and the popliteal fossa (PNS). Pairs of surface EMG electrodes were placed over tibialis anterior (TA), soleus (Sol) and Vastus Medialis (VM) muscle groups bilaterally and corticospinal (MEPs), spinal (PRR), peripheral (H-Reflex) activity and motor task response (Force) was evaluated 5 min before and after selected Paired Associative Stimulation (PAS) protocol. PAS lasted ∼14 min, and consisted of 100 pairs of transcranial magnetic stimuli applied to leg motor cortex and non-invasive, transcutaneous spinal cord stimuli to participants in the seated position.

FIGURE 2

Schematic representation of experiments 2&3 setup. Transcutaneous stimulating electrodes were placed paravertebral at landmarks over T12/L1 to L3/4 spinous processes (tSCS) and the popliteal fossa (PNS). TMS was delivered over the motor cortex region for lower limb at various interstimulus intervals following tSCS or PNS to participants in the supine position. Pairs of surface EMG electrodes were placed over tibialis anterior (TA) and soleus (Sol) muscle groups and MEP activity was recorded.

FIGURE 3

Physiological changes following PAS protocol. (A) Corticospinal excitability in the right lower leg muscles was significantly altered by PAS interval (p < 0.01, n = 22) in the TA (p < 0.001), SOL (p < 0.001) and VM (p < 0.05) following PAS_0ms. This effect was similarly identified in the (B) amplitude of H-reflexes (in the SOL muscle), significantly increased by PAS_0ms (n = 13, p < 0.05). Interestingly, (C) spinal root reflexes in the lower limb were unaffected by both PAS protocols (n = 10, p > 0.05). Each box indicates the Upper (25 percentile) and Lower (75 th percentiles), the whiskers represent the minimum and maximum values, the central line is median value and open circles represent outliers (values that are more than 1.5 of the interquartile range away from the top or bottom of the box). *p < 0.05 ***p < 0.001.

FIGURE 4

The effects of PAS on voluntary motor tasks. During ballistic dorsiflexion both muscle activation of (A) agonist/antagonist muscles and force including (B) Peak Force (PF) and Peak Rate of Force Development (PRFD) were unaffected by PAS protocols (p > 0.05, n = 11). During a force-task matching exercise (pinch and dorsiflexion) Muscle EMG (C) remained unaffected (p > 0.05, n = 11), however, (D) Force production was significantly affected (p < 0.01, n = 11) in the hand after PAS_5Ms (p < 0.05) and in the foot after PAS_0Ms (p < 0.01). Each box indicates the Upper (25 percentile) and Lower (75 th percentiles), the whiskers represent the minimum and maximum values, the central line is median value and open circles represent outliers (values that are more than 1.5 of the interquartile range away from the top or bottom of the box). *P < 0.05 **P < 0.01.

FIGURE 5

Effects of single pulses of tSCS delivered at various ISIs on TMS evoked potentials in the lower limb. (A) Example waveform average (10-control, 4-conditioned trials) EMG trace responses evoked in the TA from one participant under control (gray dashed line) and tSCS conditioned (solid black line) at each ISIs. (B) Normalized peak-to-peak MEP amplitude in the TA (black dashed line) and Sol (gray dashed line) muscles at interstimulus intervals. Mean ± SEM; *P < 0.05.

FIGURE 6

Effects of trains of tSCS (30 Hz) delivered at various ISIs on TMS evoked potentials in the lower limb. (A) Example waveform average (10-control, 4-conditioned trials) EMG responses evoked in the TA from one participant under control (gray dashed line) and tSCS/PNS conditioned (solid black line) at each ISIs. (B) Normalized peak-to-peak MEP amplitudes following either tSCS (black solid line) or PNS (gray solid line) in the TA and (C) Sol muscles at interstimulus intervals. Mean ± SEM; *P < 0.05.

FIGURE 7

The effects of two separate waveforms (Traditional tSCS and High-frequency tSCS). (A) Example waveform average (20-control, 10-conditioned trials) EMG responses evoked in the TA from single participant under control (gray dashed line) and tSCS/HF-tSCS conditioned (solid black line) with single pulses or 30 Hz trains. Normalized peak-to-peak MEP amplitudes in tSCS and HF-tSCS waveform conditions in the (B) TA and (C) Sol muscles at interstimulus intervals. Mean ± SEM; *P < 0.05; **P < 0.01; ***P < 0.001.