Pharmacological approach to the mechanisms of transcranial DC-stimulation-induced after-effects of human motor cortex excitability

Abstract

Weak transcranial direct current stimulation (tDCS) induces persisting excitability changes in the human motor cortex. These plastic excitability changes are selectively controlled by the polarity, duration and current strength of stimulation. To reveal the underlying mechanisms of direct current (DC)-induced neuroplasticity, we combined tDCS of the motor cortex with the application of Na(+)-channel-blocking carbamazepine (CBZ) and the N-methyl-D-aspartate (NMDA)-receptor antagonist dextromethorphan (DMO). Monitored by transcranial magnetic stimulation (TMS), motor cortical excitability changes of up to 40% were achieved in the drug-free condition. Increase of cortical excitability could be selected by anodal stimulation, and decrease by cathodal stimulation. Both types of excitability change lasted several minutes after cessation of current stimulation. DMO suppressed the post-stimulation effects of both anodal and cathodal DC stimulation, strongly suggesting the involvement of NMDA receptors in both types of DC-induced neuroplasticity. In contrast, CBZ selectively eliminated anodal effects. Since CBZ stabilizes the membrane potential voltage-dependently, the results reveal that after-effects of anodal tDCS require a depolarization of membrane potentials. Similar to the induction of established types of short- or long-term neuroplasticity, a combination of glutamatergic and membrane mechanisms is necessary to induce the after-effects of tDCS. On the basis of these results, we suggest that polarity-driven alterations of resting membrane potentials represent the crucial mechanisms of the DC-induced after-effects, leading to both an alteration of spontaneous discharge rates and to a change in NMDA-receptor activation.

Bilateral Transcranial Direct Current Stimulation Modulates Activation-Induced Regional Blood Flow Changes during Voluntary Movement

“…The online effects of tDCS, as we have shown here with active movements, seem to be localized under the tDCS electrodes. Because the tDCS currents used in the present study are well below threshold to induce action potentials, our results imply that the immediate effects of tDCS are detected when neurons are active and support the hypothesis that low current tDCS mainly modulates resting membrane potential thresholds (e.g., Liebetanz et al, 2002;Nitsche et al, 2003a;Zaghi et al, 2010). According to this theory, tDCS would thus modulate neuronal activation by inhibiting or facilitating the generation of action potentials.…”

Transcranial direct current stimulation may modulate extinction memory in posttraumatic stress disorder

“…Other limitations involve the possibility that our fear‐conditioning paradigm did not elicit strong conditioned responses, as well as the inability to determine possible interactions between tDCS, fear extinction processes, and psychotropic medication use in our sample, as these could influence the (after)effects of tDCS (Liebetanz, Nitsche, Tergau, & Paulus, 2002; Monte‐Silva et al., 2009; Nitsche et al., 2006, 2009). However, the focus of this pilot study was on the feasibility of combining tDCS with a PTSD‐relevant emotional learning paradigm in a real‐world clinical sample, to guide subsequent clinical research.…”

Transcranial direct current stimulation (tDCS) priming of 1Hz repetitive transcranial magnetic stimulation (rTMS) modulates experimental pain thresholds

“…tDCS does not function to induce action potentials in the neurons, but rather to influence spontaneous neuronal activity already occurring in the brain in a polarity dependent fashion [15,17,27]. Anodal tDCS has been found to induce an increase in cortical excitability via the depolarisation of neuronal membrane potentials and cathodal tDCS has been shown to decrease cortical excitability via the hyperpolarisation of these [13]. Short lasting effects of tDCS on cortical excitability are mediated by the activity of sodium and calcium channels, whereas long term after effects depend on both changes in the membrane potential and modulations of the N-methyl-D-aspartate (NMDA) and gamma-amino-butyricacid (GABA) receptor efficacy [13].…”