Determination of anodal tDCS intensity threshold for reversal of corticospinal excitability: an investigation for induction of counter-regulatory mechanisms

Transcranial direct current stimulation is applied to modulate activity, and excitability of the brain. Basically, LTP-like plasticity is induced when anodal tDCS (a-tDCS) is applied over the primary motor cortex. However, it has been shown that specific parameters of a-tDCS can induce a plasticity reversal. We aimed to systematically assess the intensity threshold for reversal of the direction of plasticity induced by a-tDCS, monitored by corticospinal excitability (CSE), and explored mechanisms regulating this reversal. Fifteen healthy participants received a-tDCS in pseudo-random order for 26 min with four intensities of 0.3, 0.7, 1, and 1.5 mA. To measure CSE changes, single-pulse TMS was applied over the left M1, and motor evoked potentials of a contralateral hand muscle were recorded prior to a-tDCS, immediately and 30-min post-intervention. Paired-pulse TMS was used to evaluate intracortical excitation and inhibition. CSE increased significantly following a-tDCS with an intensity of 0.7 mA; however, the expected effect decreased and even reversed at intensities of 1 and 1.5 mA. ICF was significantly increased while SICI and LICI decreased at 0.7 mA. On the other hand, a significant decrease of ICF, but SICI and LICI enhancement was observed at intensities of 1, and 1.5 mA. The present findings show an intensity threshold of ≥ 1 mA for 26 min a-tDCS to reverse LTP- into LTD-like plasticity. It is suggested that increasing stimulation intensity, with constant stimulation duration, activates counter-regulatory mechanisms to prevent excessive brain excitation. Therefore, stimulation intensity and plasticity induced by a-tDCS might non-linearly correlate in scenarios with prolonged stimulation duration.