Abstract

Introduction Excitability and connectivity in the human motor network comprising the supplementary motor area (SMA) and primary motor cortex (M1) are important for voluntary movement generation and rehabilitation of lost motor function after stroke. Previously, we demonstrated that paired associative stimulation of SMA and M1 (SMA–M1-PAS) by dual coil transcranial magnetic stimulation (TMS) may induce LTP-like plasticity in this network (Arai et al., 2011. J Neurosci 31:15376–83). Here, we tested the influence of simultaneous modulation of general network excitability by transcranial direct current stimulation (tDCS) on associative SMA–M1 plasticity. Methods 12 healthy right-handed male subjects took part in this pseudo-randomized,single-blinded, crossover study. Subjects received two blocks (spaced by 5 min) of 50 pairs of neuronavigated SMA-before-M1 PAS at an interstimulus interval of 6 ms and intertrial interval of 5 s. Simultaneously we applied anodal, cathodal, or sham tDCS over the left M1 in three different sessions, at least 1 week apart. Associative SMA–M1 plasticity was quantified by changes in (i) motor-evoked potentials (MEP) in the right first dorsal interosseus muscle, and (ii) SMA-to-M1 connectivity (ratio of SMA-conditioned/unconditioned MEPs), at baseline versus for up to two hours after the intervention. Results SMA–M1-PAS resulted in an expected LTP-like MEP amplitude increase in 9 of 12 subjects in the sham tDCS condition. In 7 of these 9 SMA–M1-PAS responders, the LTP-like MEP amplitude increase was suppressed or even turned into depression both in the anodal and cathodal tDCS condition. In contrast, in all three non-responders anodal and cathodal tDCS led to less MEP suppression or even turned it into facilitation. Likewise, in 7 (anodal tDCS) and 6 (cathodal tDCS) of the 8 subjects who showed a facilitation of SMA-to-M1 connectivity in the sham tDCS condition this connectivity was reduced in the anodal and cathodal tDCS conditions, whereas it was less reduced or even facilitated in 2 (anodal tDCS) and all (cathodal tDCS) of the 4 subjects showing a reduction of SMA-to-M1 connectivity in the sham condition. Conclusion Our results demonstrate a reversing interaction between general network excitability modulation by tDCS and associative plasticity in the human SMA–M1 network, independent of the polarity of tDCS.

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