GABAergic modulation of DC stimulation-induced motor cortex excitability shifts in humans.
Weak transcranial DC stimulation (tDCS) of the human motor cortex results in excitability shifts during and after the end of stimulation, which are most probably localized intracortically. Anodal stimulation enhances excitability, whereas cathodal stimulation reduces it. Although the after-effects of tDCS are NMDA receptor-dependent, nothing is known about the involvement of additional receptors. Here we show that pharmacological strengthening of GABAergic inhibition modulates selectively the after-effects elicited by anodal tDCS. Administration of the GABA(A) receptor agonist lorazepam resulted in a delayed, but then enhanced and prolonged anodal tDCS-induced excitability elevation. The initial absence of an excitability enhancement under lorazepam is most probably caused by a loss of the anodal tDCS-generated intracortical diminution of inhibition and enhancement of facilitation, which occurs without pharmacological intervention. The reasons for the late-occurring excitability enhancement remain unclear. Because intracortical inhibition and facilitation are not changed in this phase compared with pre-tDCS values, excitability changes originating from remote cortical or subcortical areas could be involved.
Nitsche
Michael A
MA
Department of Clinical Neurophysiology, University of Goettingen, Robert Koch Str. 40, 37075 Goettingen, Germany.
Liebetanz
David
D
Schlitterlau
Anett
A
Henschke
Undine
U
Fricke
Kristina
K
Frommann
Kai
K
Lang
Nicolas
N
Henning
Stefan
S
Paulus
Walter
W
Tergau
Frithjof
F
D000328:Adult; D000704:Analysis of Variance; D016022:Case-Control Studies; D004558:Electric Stimulation; D004566:Electrodes / Q000145:classification / Q000600:supply & distribution; D019054:Evoked Potentials, Motor / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D018757:GABA Modulators / Q000494:pharmacology*; D006801:Humans; D008140:Lorazepam / Q000494:pharmacology*; D008280:Magnetics; D008297:Male; D009044:Motor Cortex / Q000187:drug effects* / Q000528:radiation effects*; D009433:Neural Inhibition / Q000187:drug effects / Q000528:radiation effects; D010919:Placebos / Q000494:pharmacology; D011897:Random Allocation; D013997:Time Factors
D018757:GABA Modulators; D010919:Placebos; D008140:Lorazepam