Combined neuromuscular electrical stimulation and transcutaneous spinal direct current stimulation increases motor cortical plasticity in healthy humans

Abstract

Introduction: Neuromuscular electrical stimulation (NMES) induces neural plasticity of the central nervous system (CNS) and improves motor function in patients with CNS lesions. However, the extended stimulus duration of NMES reduces its clinical applicability. Transcutaneous spinal direct current stimulation (tsDCS), which increases afferent input, may enhance the effects and reduce the stimulus duration of NMES. This study investigated the excitability of the motor cortex, somatosensory cortex, and spinal motor neurons after the combined stimulation of NMES and tsDCS.

Methods: Among the 55 participants in this study, 24 were allocated to experiment 1, 15 to experiment 2, and 16 to experiment 3. They received intervention for 20 min on different days: (1) NMES combined with tsDCS (NMES + tsDCS), (2) NMES combined with sham tsDCS (NMES + sham tsDCS), and (3) sham NMES combined with tsDCS (sham NMES + tsDCS). NMES was delivered to the right common peroneal nerve at 25 Hz with the intensity at 120% of the motor threshold. For tsDCS, the cathodal electrode was positioned on the thoracic 10th-12th vertebral levels, and the anodal electrode was located on the right shoulder. The stimulus intensity was 2.5 mA. In experiment 1, motor evoked potentials (MEPs) and short-latency intracortical inhibition (SICI) were measured by transcranial magnetic stimulation up to 60 min after stimulation. The spinal motor neurons' excitability was assessed by recording the posterior root muscle reflex (PRMR) induced via transcutaneous spinal cord stimulation in experiment 2, and the primary somatosensory cortex excitability was evaluated by recording the somatosensory evoked potentials (SEPs) in experiment 3 up to 15 min after stimulation.

Results: Compared to before the stimulation, NMES + tsDCS significantly increased MEP for 60 min or more, and significantly decreased SICI immediately after. Conversely contrast, the PRMR significantly decreased immediately after, and SEPs were unchanged.

Discussion: These results suggest that simultaneous afferent inputs from different stimulus positions critically induce primary motor cortex plasticity. The combined stimulation of NMES with tsDCS may facilitate the development of a new neurorehabilitation technique.

Keywords: afferent input; corticospinal projection; motor cortical excitability; neural plasticity; spinal excitability.

FIGURE 1

Experimental procedure. The participants received neuromuscular electrical stimulation (NMES) + transcutaneous spinal direct current stimulation (tsDCS), NMES + sham tsDCS, or sham NMES + tsDCS (experiments 1, 2, and 3, respectively) in 20 min session conducted on different days. In experiment 1, motor evoked potentials (MEPs) and short-interval intracortical inhibition (SICI) were measured at baseline, before the intervention (T0), and after the intervention at 0 min (T1), 15 min (T2), 30 min (T3), and 60 min (T4). In experiment 2, maximum M-wave (M-max) and posterior root muscle reflex (PRMR) were measured at baseline, T0, T1, and T2. In experiment 3, somatosensory evoked potentials (SEPs) were measured at baseline, T0, T1, and T2.

FIGURE 2

The raw data of somatosensory evoked potentials (SEPs). The peaks of the SEPs were labeled based on latency from the stimulus onset for peak-to-peak analysis. P30 was defined as a positive peak with a latency of around 39 ms (39 ± 5 ms). N40 was defined as a negative peak following P30 and with a latency of around 45 ms (45 ± 5 ms).

FIGURE 3

The combined effects of neuromuscular electrical stimulation (NMES) and transcutaneous spinal direct current stimulation (tsDCS) on motor evoked potentials (MEPs) and short-interval intracortical inhibition (SICI). (A) Represents the MEPs changes before and after the intervention. MEP amplitudes were normalized to baseline MEP amplitudes. (B) Represents the SICI changes before and after the intervention. Conditioned MEP amplitudes were normalized to test MEP amplitudes to calculate SICI. NMES + tsDCS is denoted as dark gray boxes, NMES + sham tsDCS is denoted as light gray boxes, and sham NMES + tsDCS is denoted as white boxes. The median value and interquartile ranges are represented by horizontal lines within boxes and whiskers representing minimum and maximum values, respectively. Asterisks indicate significant differences compared to “T0” (P < 0.05).

FIGURE 4

Raw traces of posterior root muscle reflex (PRMR) waveforms from the right tibialis anterior muscle were obtained from a participant before and after neuromuscular electrical stimulation (NMES) + transcutaneous spinal direct current stimulation (tsDCS); NMES + sham tsDCS; and sham NMES + tsDCS. Each waveform represents the average of five trials.