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

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

Aberrant crossed corticospinal facilitation in muscles distant from a spinal cord injury.

Crossed facilitatory interactions in the corticospinal pathway are impaired in humans with chronic incomplete spinal cord injury (SCI). The extent to which crossed facilitation is affected in muscles above and below the injury remains unknown. To address this question we tested 51 patients with neurological injuries between C2-T12 and 17 age-matched healthy controls. Using transcranial magnetic stimulation we elicited motor evoked potentials (MEPs) in the resting first dorsal interosseous, biceps brachii, and tibialis anterior muscles when the contralateral side remained at rest or performed 70% of maximal voluntary contraction (MVC) into index finger abduction, elbow flexion, and ankle dorsiflexion, respectively. By testing MEPs in muscles with motoneurons located at different spinal cord segments we were able to relate the neurological level of injury to be above, at, or below the location of the motoneurons of the muscle tested. We demonstrate that in patients the size of MEPs was increased to a similar extent as in controls in muscles above the injury during 70% of MVC compared to rest. MEPs remained unchanged in muscles at and within 5 segments below the injury during 70% of MVC compared to rest. However, in muscles beyond 5 segments below the injury the size of MEPs increased similar to controls and was aberrantly high, 2-fold above controls, in muscles distant (>15 segments) from the injury. These aberrantly large MEPs were accompanied by larger F-wave amplitudes compared to controls. Thus, our findings support the view that corticospinal degeneration does not spread rostral to the lesion, and highlights the potential of caudal regions distant from an injury to facilitate residual corticospinal output after SCI

Grasp-specific motor resonance is influenced by the visibility of the observed actor

Motor resonance is the modulation of M1 corticospinal excitability induced by observation of others' actions. Recent brain imaging studies have revealed that viewing videos of grasping actions led to a differential activation of the ventral premotor cortex depending on whether the entire person is viewed versus only their disembodied hand. Here we used transcranial magnetic stimulation (TMS) to examine motor evoked potentials (MEPs) in the first dorsal interosseous (FDI) and abductor digiti minimi (ADM) during observation of videos or static images in which a whole person or merely the hand was seen reaching and grasping a peanut (precision grip) or an apple (whole hand grasp). Participants were presented with six visual conditions in which visual stimuli (video vs static image), view (whole person vs hand) and grasp (precision grip vs whole hand grasp) were varied in a 2 × 2 × 2 factorial design. Observing videos, but not static images, of a hand grasping different objects resulted in a grasp-specific interaction, such that FDI and ADM MEPs were differentially modulated depending on the type of grasp being observed (precision grip vs whole hand grasp). This interaction was present when observing the hand acting, but not when observing the whole person acting. Additional experiments revealed that these results were unlikely to be due to the relative size of the hand being observed. Our results suggest that observation of videos rather than static images is critical for motor resonance. Importantly, observing the whole person performing the action abolished the grasp-specific effect, which could be due to a variety of PMv inputs converging on M1

Selective Effects of Baclofen on Use-Dependent Modulation of GABAB Inhibition after Tetraplegia

Baclofen is a GABA B receptor agonist commonly used to relief spasticity related to motor disorders. The effects of baclofen on voluntary motor output are limited and not yet understood. Using noninvasive transcranial magnetic and electrical stimulation techniques, we examined electrophysiological measures probably involving GABA B (long-interval intracortical inhibition and the cortical silent period) and GABA A (short-interval intracortical inhibition) receptors, which are inhibitory effects mediated by subcortical and cortical mechanisms. We demonstrate increased active long-interval intracortical inhibition and prolonged cortical silent period during voluntary activity of an intrinsic finger muscle in humans with chronic incomplete cervical spinal cord injury (SCI) compared with age-matched controls, whereas resting long-interval intracortical inhibition was unchanged. However, long-term (∼6 years) use of baclofen decreased active long-interval intracortical inhibition to similar levels as controls but did not affect the duration of the cortical silent period. We found a correlation between signs of spasticity and long-interval intracortical inhibition in patients with SCI. Short-interval intracortical inhibition was decreased during voluntary contraction compared with rest but there was no effect of SCI or baclofen use. Together, these results demonstrate that baclofen selectively maintains use-dependent modulation of largely subcortical but not cortical GABA B neuronal pathways after human SCI. Thus, cortical GABA B circuits may be less sensitive to baclofen than spinal GABA B circuits. This may contribute to the limited effects of baclofen on voluntary motor output in subjects with motor disorders affected by spasticity

Locomotor adaptation and aftereffects in patients with reduced somatosensory input due to peripheral neuropathy.

We studied 12 peripheral neuropathy patients (PNP) and 13 age-matched controls with the “broken escalator” paradigm to see how somatosensory loss affects gait adaptation and the release and recovery (“braking”) of the forward trunk overshoot observed during this locomotor aftereffect. Trunk displacement, foot contact signals, and leg electromyograms (EMGs) were recorded while subjects walked onto a stationary sled (BEFORE trials), onto the moving sled (MOVING or adaptation trials), and again onto the stationary sled (AFTER trials). PNP were unsteady during the MOVING trials, but this progressively improved, indicating some adaptation. During the after trials, 77% of control subjects displayed a trunk overshoot aftereffect but over half of the PNP (58%) did not. The PNP without a trunk aftereffect adapted to the MOVING trials by increasing distance traveled; subsequently this was expressed as increased distance traveled during the aftereffect rather than as a trunk overshoot. This clear separation in consequent aftereffects was not seen in the normal controls suggesting that, as a result of somatosensory loss, some PNP use distinctive strategies to negotiate the moving sled, in turn resulting in a distinct aftereffects. In addition, PNP displayed earlier than normal anticipatory leg EMG activity during the first after trial. Although proprioceptive inputs are not critical for the emergence or termination of the aftereffect, somatosensory loss induces profound changes in motor adaptation and anticipation. Our study has found individual differences in adaptive motor performance, indicative that PNP adopt different feed-forward gait compensatory strategies in response to peripheral sensory loss

MEPs above the injury site.

<p>MEPs recorded from the resting BB and FDI of representative patients with a T3-T5 (A) and T6-T12 (B) injury, while the other side remained at rest or performed 70% of index finger abduction or elbow flexion. Group data (C, healthy controls, n=17 and T3-T5, n=6; D, healthy controls, n=17 and T6-T12, n=14). The abscissa shows the muscle tested (BB and FDI). The ordinate shows the size of FDI and BB MEPs as a % of the baseline FDI and BB MEPs. Note that the increase in FDI and BB MEP size during contralateral index finger abduction and elbow flexion in both groups of patients was similar to healthy controls. Error bars indicate SEs. *p<i><</i>0.05.</p

Segmental level of injury and MEPs.

<p>Schematics of the spinal cord illustrating segments above the injury (white area), at the injury site (black shaded area), within 5 segment below the injury (dark gray shaded area) and greater than 5 segments below the injury site (5-8 segments light shaded area; 17-23 segments light gray-striped area). (B) MEPs recorded from the BB, FDI, and TA in all motor tasks and patients tested are plotted as a function of the segmental level of injury. The abscissa shows the number of segments (grouped by 3 segments) from all muscles tested. The ordinate shows the size of MEPs as a % of the baseline MEPs in all muscles. Note that when the muscle tested was at or within 5 segments below the injury the size of MEPs remained unchanged during 70% of MVC compared to rest. Whereas, when the muscle tested was more than 5 segments below the injury the size of MEPs was increased and aberrantly high at longer distances during 70% of MVC compared to rest. Error bars indicate SEs. </p

MEPs below the injury site.

<p>MEPs recorded from the resting BB, FDI, and TA of representative patients with a C2-C4 (A) and C5-C7 injury (B), while the other side remained at rest or performed 70% of index finger abduction, elbow flexion, or ankle dorsiflexion. Group data (C, healthy controls, n=17 and C2-C4, n=7; D, healthy controls, n=16 and C5-T7, n=11). The abscissa shows the muscle tested (BB, FDI, and TA). The ordinate shows the size of BB, FDI, and TA MEPs as a % of the baseline BB, FDI and TA MEPs. Note the increase in FDI and TA MEP size during contralateral index finger abduction and elbow flexion, but not in BB MEPs during elbow flexion in patients with C2-C4 injuries. Interestingly, TA MEPs size was increased in both groups of patients more than in healthy controls. Error bars indicate SEs. *p<i><</i>0.05.</p

MEPs at the injury site.

<p>(A) MEPs recorded from the resting BB and FDI of representative patients with a C5-C6 and C8-T1 SCI, while the other side remained at rest or performed 70% of elbow flexion or index finger abduction. Group data (B, healthy controls, n=17; C5-C6, n=9, C8-T1, n=5). The abscissa shows the muscle tested (BB and FDI). The ordinate shows the size of BB and FDI MEPs as a % of the baseline BB and FDI MEPs. Note the increase in BB and FDI MEP size during contralateral index finger abduction and elbow flexion in healthy controls, but not in patients with C5-C6 and C8-T1 SCI. Error bars indicate SEs. *p<i><</i>0.05.</p