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

Abstract

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.

Timing is everything: event-related transcranial direct current stimulation improves motor adaptation

“…In contrast, event-related TDCS may selectively modulate only those circuits and task-related synapses that are contemporaneously active and undergoing concurrent plasticity [16,41]. As such, er-TDCS could prove beneficial when long experimental or rehabilitative protocols are required, as recent research suggests that long continuous bouts of TDCS may cause the resultant modulatory effects to diminish and even reverse over time, i.e., from excitation to inhibition [42]. Neural recording studies have also found that the effects of direct current stimulation may attenuate during long stimulation blocks.…”

Effect of a tailored upper extremity strength training intervention combined with direct current stimulation in chronic stroke survivors: A Randomized Controlled Trial

“…Also, a higher tDCS intensity has been shown to reverse tDCS-induced neuroplastic effects in healthy people (63)(64)(65). For example, Hassanzahraee et al found that stimulation >1 mA for 26 min resulted in a reversal of anodal tDCS effects and was associated with a decrease in MEP amplitude and an increase in short-interval intracortical inhibition (63). However, these effects were also shown subsequently to be linked with the duration of the application (64), duration >26 min leading to a reversal of anodal stimulation.…”

Letter to the editor: Reducing seizure frequency in patients with refractory epilepsy with cathodal transcranial direct current stimulation

“…When using tDCS as a neuromodulatory technique for therapeutic purposes, it should be noted that the higher intensities or longer durations do not necessarily increase the expected effect of the used protocol [6,8]. It is important to know that the threshold for reaching the physiological limit for the reversal of the effect can be quite different in healthy population compared to patient populations which may be dependent on the synaptic history in the neurons in the stimulated area.…”