Paired Associative Electroacupuncture and Transcranial Magnetic Stimulation in Humans.

Yi Huang,Ming-Kuei Lu,Jui-Cheng Chen,Chon-Haw Tsai,Chun-Ming Chen

doi:10.3389/fnhum.2019.00049

Abstract

Pairing transcutaneous electric nerve stimulation (TENS) and transcranial magnetic stimulation (TMS) with specific stimulus-intervals induces associative motor plasticity at the primary motor cortex (M1). Electroacupuncture (EA) is an established medical technique in the eastern countries. This study investigates whether EA paired with TMS induces distinct M1 motor plasticity. Fifteen healthy, right-handed subjects (aged 23.6 ± 2.0 years, eight women) were studied. Two-hundred and twenty-five pairs of TMS of the left M1 preceded by right EA at acupoint “Neiguan” [Pericardium 6 (PC6), located 2 decimeters proximal from the wrist wrinkle] were respectively applied with the interstimulus interval (ISI) of individual somatosensory evoked potential (SSEP) N20 latency plus 2 ms (N20+2) and minus 5 ms (N20-5) with at least 1-week interval. The paired stimulation was delivered at a rate of 0.25 Hz. Sham TMS with a sham coil was adopted to examine the low-frequency EA influence on M1 in eleven subjects. M1 excitability was assessed by motor-evoked potential (MEP) recruitment curve with five TMS intensity levels, short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and cerebellar inhibition (CBI) at the abductor pollicis brevis (APB) muscle of the right hand before and after the EA-M1 paired associative stimulation (PAS). In addition, median nerve SSEPs and H-reflex were respectively measured to monitor somatosensory and spinal excitability. The MEP showed significantly facilitated after the sham EA-M1 PAS while tested with 80% of the TMS intensity producing on average 1 mV amplitude (i.e., MEP1 mV) in the resting APB muscle. It was also facilitated while tested with 90% MEP1 mV irrespective of the stimulation conditions. The SSEP showed a higher amplitude from the real EA-M1 PAS compared to that from the sham EA-M1 PAS. No significant change was found on SICI, ICF, CBI and H-reflex. Findings suggest that repetitive low frequency EA paired with real TMS did not induce spike-timing dependent motor plasticity but EA paired with sham TMS induced specific M1 excitability change. Complex sensory afferents with dispersed time locked to the sensorimotor cortical area could hamper instead of enhancing the induction of the spike-timing dependent plasticity (STDP) in M1.

Highlights

Primary motor cortex (M1) receives multi-direction gated sensory information and executes the final motor command in humans (Cheng et al, 2017; Lei et al, 2018)
RmANOVA of the motor-evoked potential (MEP) amplitude revealed a significant effect of TIME (F(1,14) = 8.8, P = 0.01) and a significant CONDITION × TIME interaction at transcranial magnetic stimulation (TMS) intensity of 80% MEP1 mV (F(1,14) = 5.63, P = 0.03), and a significant effect of TIME at TMS intensity of 90% MEP1 mV (F(1,14) = 12.73, P = 0.003; Table 2)
Repetitive EA paired with sham TMS at M1 induces specific motor cortical plasticity which could be only detectable with moderate TMS intensities

Summary

Introduction

Primary motor cortex (M1) receives multi-direction gated sensory information and executes the final motor command in humans (Cheng et al, 2017; Lei et al, 2018) It plays a key role in motor learning and motor performance. The most traditional form of PAS consists of repeated pairing of a single electric stimulus at the peripheral median nerve and a TMS pulse on the contralateral M1 with a specific interstimulus interval (ISI) between these two stimuli. It induces aftereffects representing the associative long-term potentiation (LTP)- and depression (LTD)-like phenomenon that bears resemblance to spike-timing dependent plasticity (STDP) as it has been elaborated in animal models (Carson and Kennedy, 2013). The electric stimulation is prone to be adapted for most of the subjects so an additional device for maintaining the subject’s attention during the experiment is usually required (Stefan et al, 2004; Lu et al, 2009)

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