Modulating parameters of excitability during and after transcranial direct current stimulation of the human motor cortex

Abstract

Weak transcranial direct current stimulation (tDCS) of the human motor cortex results in excitability shifts which occur during and after stimulation. These excitability shifts are polarity-specific with anodal tDCS enhancing excitability, and cathodal reducing it. To explore the origin of this excitability modulation in more detail, we measured the input-output curve and motor thresholds as global parameters of cortico-spinal excitability, and determined intracortical inhibition and facilitation, as well as facilitatory indirect wave (I-wave) interactions. Measurements were performed during short-term tDCS, which elicits no after-effects, and during other tDCS protocols which do elicit short- and long-lasting after-effects. Resting and active motor thresholds remained stable during and after tDCS. The slope of the input-output curve was increased by anodal tDCS and decreased by cathodal tDCS. Anodal tDCS of the primary motor cortex reduced intracortical inhibition and enhanced facilitation after tDCS but not during tDCS. Cathodal tDCS reduced facilitation during, and additionally increased inhibition after its administration. During tDCS, I-wave facilitation was not influenced but, for the after-effects, anodal tDCS increased I-wave facilitation, while cathodal tDCS had only minor effects. These results suggest that the effect of tDCS on cortico-spinal excitability during a short period of stimulation (which does not induce after-effects) primarily depends on subthreshold resting membrane potential changes, which are able to modulate the input-output curve, but not motor thresholds. In contrast, the after-effects of tDCS are due to shifts in intracortical inhibition and facilitation, and at least partly also to facilitatory I-wave interaction, which is controlled by synaptic activity.

Figure 1. tDCS shifts the slope of the input–output curve polarity-specifically

The MEP amplitudes (means ±s.e.m.) at 100, 110, 130 and 150% of resting MT (RMT) are shown for the intra-tDCS conditions (A) and the short- (B) and long-lasting (C) after-effects. During tDCS, cathodal stimulation diminishes the MEP-amplitude relative to no-tDCS values, whereas anodal tDCS tends to enhance it. Due to the experimental protocol, the no-tDCS (non) curves used for comparisons in the anodal and cathodal intra-tDCS conditions are identical (applies also to the following figures). For the after-effects, the direction of the current-induced MEP amplitude changes is similar to the effects during stimulation, but the anodal tDCS-elicited effects are more clear-cut here. Here, no-tDCS (non) values represent the ‘before-tDCS’ baselines and are different for the anodal and cathodal conditions (applies also to the following figures). *P < 0.05, Fisher's LSD test, comparing the respective tDCS and no-tDCS values.

Figure 2. Intracortical inhibition and facilitation is modulated by tDCS

The single-pulse standardized double-stimulation MEP amplitude ratios ±s.e.m. are depicted for ISIs revealing inhibitory (ISIs of 2, 3 and 5 ms) and facilitatory (ISIs of 10 and 15 ms) effects for the different tDCS protocols. A, during a short tDCS, which elicits no after-effects, anodal stimulation does not shift inhibition and facilitation relative to the no-tDCS (non) values. Cathodal stimulation reduces facilitation for the ISI of 15 ms. B, however, during the short-lasting after-effects, cathodal stimulation reduces the amplitude of all ISIs tested, whereas anodal tDCS results in reversed effects, thus reducing inhibition and increasing facilitation. C, for the long-lasting after-effects, the principal effect is identical, but not all ISIs are modulated here by tDCS significantly. *P < 0.05, Fisher's LSD test, comparing the respective tDCS and no-tDCS values.

Figure 3. I-wave facilitation is modulated by tDCS

Single pulse-standardized double-stimulation MEP amplitude ratios ±s.e.m. are depicted for I-wave facilitation within the different tDCS protocols. A, during a short tDCS, which elicits no after-effects, it does not shift I-wave facilitation relative to the no-tDCS (non) values. B, for the short-lasting after-effects, cathodal tDCS does not modulate I-wave peaks, whereas anodal tDCS results in a separation of I-wave peak-values. C, for the long-lasting after-effects, anodal and cathodal tDCS increase the first I-wave peaks, while only anodal tDCS increases the fourth I-wave peak. *P < 0.05, Fisher's LSD test, comparing the respective tDCS and no-tDCS values.