Paired Associative Electroacupuncture and Transcranial Magnetic Stimulation in Humans

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., MEP_{1 mV}) in the resting APB muscle. It was also facilitated while tested with 90% MEP_{1 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.

Keywords: electroacupuncture; motor cortex; motor evoked potential; paired associative stimulation; transcranial magnetic stimulation.

Figure 1

Localization of the acupoint “Neiguan” (Pericardium 6, PC6; *).

Figure 2

Experimental design and the time line of the paired associative electroacupuncture and transcranial magnetic stimulation (TMS; PAET) study.

Figure 3

Post hoc comparisons of the motor evoked potential (MEP) evoked with different TMS intensities for the 15 subjects. MEP_{1 mV} means the TMS intensity inducing on average 1 mV MEP amplitude in the resting abductor pollicis brevis (APB) muscle. The MEP amplitude showed a significant facilitation after the sham PAET intervention with 80% MEP_{1 mV} and the PAET intervention with 90% MEP_{1 mV}. Data are shown by means ± standard errors. **P < 0.01 by paired t-test with Bonferroni’s correction.

Figure 4

Post hoc comparisons of the intracortical facilitation (ICF) and somatosensory evoked potential (SSEP). The ICF comparisons did not show any significant difference. The SSEP amplitude of the real condition was significantly higher than that of the sham condition. Data are shown by means ± standard errors. **P < 0.01 by paired t-test with Bonferroni’s correction.