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

Abstract

Introduction: Weak direct current stimulation (tDCS) of the human motor cortex results in excitability shifts which occur during and after stimulation. These are polarity-specific with anodal tDCS enhancing excitability, and cathodal reducing it. To explore the origin of this excitability modulation, 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) interaction. Measurements were performed during short-term tDCS, which elicits no after-effects, and for tDCS-protocols eliciting short- and long-lasting after-effects. Methods: Twelve to twenty healthy human subjects participated in each experiment. Active and resting motor threshold, input/output curve, short-term interval inhibition/facilitation and I-wave interaction were measured by transcranial magnetic stimulation (TMS) standard paradigms. Motor cortex excitability was evaluated during short-lasting tDCS, which elicits no after-effects (4s anodal or cathodal stimulation), and for short-lasting (7min tDCS) and long-lasting (9min cathodal, 13min anodal tDCS) after-effects. Results: Resting and active motor thresholds remained stable during and after tDCS. The slope of the input/output curve was increased by anodal and decreased by cathodal tDCS. Anodal tDCS of the primary motor cortex reduced intracortical inhibition and enhanced facilitation after, but not during tDCS, while cathodal tDCS reduced facilitation during and additionally increased inhibition after its administration. During tDCS, I-wave (indirect wave) facilitation was not influenced, but for the after-effects anodal tDCS increased I-wave facilitation, while cathodal tDCS had only minor effects. Discussion: These results suggest that the effect of tDCS on cortico-spinal excitability during a short stimulation, which does not induce after-effects, primarily depends on subthreshold resting membrane potential changes, which 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 are controlled by synaptic activity.