Nitsche M A, Fricke K, Henschke U, Schlitterlau A, Liebetanz D, Lang N, Henning S, Tergau F, Paulus W
Department of Clinical Neurophysiology, Georg-August-University, Goettingen, Germany.
J Physiol. 2003 Nov 15;553(Pt 1):293-301. doi: 10.1113/jphysiol.2003.049916. Epub 2003 Aug 29.
Transcranial direct current stimulation (tDCS) of the human motor cortex results in polarity-specific shifts of cortical excitability during and after stimulation. Anodal tDCS enhances and cathodal stimulation reduces excitability. Animal experiments have demonstrated that the effect of anodal tDCS is caused by neuronal depolarisation, while cathodal tDCS hyperpolarises cortical neurones. However, not much is known about the ion channels and receptors involved in these effects. Thus, the impact of the sodium channel blocker carbamazepine, the calcium channel blocker flunarizine and the NMDA receptor antagonist dextromethorphane on tDCS-elicited motor cortical excitability changes of healthy human subjects were tested. tDCS-protocols inducing excitability alterations (1) only during tDCS and (2) eliciting long-lasting after-effects were applied after drug administration. Carbamazepine selectively eliminated the excitability enhancement induced by anodal stimulation during and after tDCS. Flunarizine resulted in similar changes. Antagonising NMDA receptors did not alter current-generated excitability changes during a short stimulation, which elicits no after-effects, but prevented the induction of long-lasting after-effects independent of their direction. These results suggest that, like in other animals, cortical excitability shifts induced during tDCS in humans also depend on membrane polarisation, thus modulating the conductance of sodium and calcium channels. Moreover, they suggest that the after-effects may be NMDA receptor dependent. Since NMDA receptors are involved in neuroplastic changes, the results suggest a possible application of tDCS in the modulation or induction of these processes in a clinical setting. The selective elimination of tDCS-driven excitability enhancements by carbamazepine proposes a role for this drug in focussing the effects of cathodal tDCS, which may have important future clinical applications.
经颅直流电刺激（tDCS）作用于人类运动皮层时，在刺激期间及之后会导致皮层兴奋性发生极性特异性变化。阳极tDCS增强兴奋性，阴极刺激则降低兴奋性。动物实验表明，阳极tDCS的效应是由神经元去极化引起的，而阴极tDCS使皮层神经元超极化。然而，对于这些效应所涉及的离子通道和受体，人们了解得并不多。因此，测试了钠通道阻滞剂卡马西平、钙通道阻滞剂氟桂利嗪和N-甲基-D-天冬氨酸（NMDA）受体拮抗剂右美沙芬对健康人类受试者tDCS诱发的运动皮层兴奋性变化的影响。在给药后应用了能诱导兴奋性改变的tDCS方案：（1）仅在tDCS期间，以及（2）引发持久后效应的方案。卡马西平选择性地消除了tDCS期间及之后阳极刺激所诱导的兴奋性增强。氟桂利嗪也导致了类似的变化。拮抗NMDA受体在短时间刺激期间（该刺激不会引发后效应）并未改变电流诱发的兴奋性变化，但阻止了持久后效应的诱导，且与后效应的方向无关。这些结果表明，与其他动物一样，人类tDCS期间诱发的皮层兴奋性变化也取决于膜极化，从而调节钠通道和钙通道的电导。此外，这些结果表明后效应可能依赖于NMDA受体。由于NMDA受体参与神经可塑性变化，这些结果提示tDCS在临床环境中对这些过程的调节或诱导可能具有潜在应用价值。卡马西平对tDCS驱动的兴奋性增强的选择性消除表明该药物在聚焦阴极tDCS的效应方面具有作用，这可能在未来具有重要的临床应用。
