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 (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.

Neural Substrates of Transcutaneous Spinal Cord Stimulation: Neuromodulation across Multiple Segments of the Spinal Cord

“…Further study is required for understanding the effects of multisite tSCS in individuals living with an SCI, as well as its effects on spasticity both within a session and after training. Interestingly, in neurologically intact study participants, modulated tSCS was unable to alter the excitability of either H-reflexes or MEPs when combined with either arm or leg cycling, regardless of whether single-site or multisite tSCS was applied [70,82]. This indicates that in neurologically intact individuals where interlimb coordination and the corticospinal tract are intact, the effects of arm or leg cycling on cervicolumbar coupling and corticospinal drive were not impacted significantly by the tSCS intensity used.…”

“…This is similar to our recent investigation, which found that modulated tSCS (33 Hz trains of 1 m long pulses with a 10 kHz carrier frequency) applied over the C3-4 and C6-7 spinous processes in neurologically intact individuals did not alter MEPs assessed in the forearm flexors [69]. Moreover, data from a paired associative stimulation (PAS) paradigm involving single pulses of transcranial magnetic stimulation (TMS) and unmodulated tSCS arriving at the same time at spinal motor neurons revealed increases in corticospinal excitability, but facilitation of MEPs following tSCS was less pronounced when tSCS pulses were filled with a carrier frequency [70]. These studies highlight the fact that in the presence of a carrier frequency, tSCS may be unable to facilitate MEPs.…”

“…Evidence indicates that tSCS alters the excitability of multiple segments of the spinal cord [70,82]. These multi-segmental effects were specifically investigated in our recent work exploring how stimulation alters excitability across multiple levels of the spinal cord in neurologically intact participants, using the setup described in Figure 3.…”

Effect of Cervical Transcutaneous Spinal Cord Stimulation on Sensorimotor Cortical Activity during Upper-Limb Movements in Healthy Individuals

“…Numerous studies have investigated tSCS modulation at both the cortical and spinal level [7][8][9][10][11][12][13]. Benavides et al, for example, investigated cortical modulation by comparing motor evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS) before and after 20 min of tSCS.…”

The effects of transcutaneous spinal cord stimulation delivered with and without high‐frequency modulation on spinal and corticospinal excitability

“…To deliver high currents with less discomfort, some groups deliver TSCS modulated with high frequencies ranging from 5 to 10 kHz. [18][19][20] While higher current intensities could be tolerated when the TSCS was modulated with a kHz frequency (TSCS-kHz), much higher currents were also required to reach PRR threshold (~180-200 mA for TSCS-kHz, compared with ~50 mA for TSCS 21,22 ), due to the TSCS-kHz waveform being active for half the duration of the TSCS waveform, and the apparently reduced neural recruitment efficiency with TSCS-kHz. 23 TSCS-kHz interventions are typically delivered in the range 60-120 mA 19,24 ; therefore, they are delivered at considerably subthreshold intensities with respect to the PRR threshold (~40%).…”