The main finding of the present study is that 20 min of anodal tDCS can significantly shorten the duration of the CSP. Conversely, despite an increase in corticospinal excitability reflected in greater MEP size, anodal tDCS failed to modulate LICI, another presumed measure of GABAB inhibition.
The present study is, to our knowledge, the first to show that anodal tDCS can reduce CSP duration. This is in contrast with a previous study, in which anodal tDCS failed to modulate CSP duration 7. This discrepancy could be due in part to differences in stimulation parameters and protocol. Indeed, in previous studies, stimulation intensity, duration and electrode sizes varied considerably from the ones used here (1.5 mA; 20 min, 25 cm2 for M1 stimulation and 35 cm2 for supraorbital stimulation). Moreover, participants in one of the studies suffered from chronic pain 6, hindering the generalizability of the results. The effect of cathodal stimulation on CSP is also unclear. Hasan et al. 9 reported that 9 min of cathodal tDCS could increase duration of the CSP in a sample of healthy participants, whereas another study 7 reported no impact of 10 min of cathodal tDCS on CSP duration in healthy participants. It should also be mentioned that the strength of the isometric muscle contraction was not adjusted post-tDCS in the present study. As such, tDCS may have modified absolute strength exerted by the participants and led to the increase in CSP duration.
Theoretically, an increase in excitability could be explained by either enhanced excitatory transmission, or a reduction of inhibitory transmission 15. A recent magnetic resonance spectroscopy study reported a decrease of GABA levels after tDCS, but no impact on glutamate 13, suggesting that intracortical inhibition rather than excitatory transmission could be specifically affected by tDCS and partially responsible for changes in cortical excitability. This is concordant with the reduction of GABAB synaptic activity observed here. The mechanism underlying this reduction of inhibitory transmission is thought to result from the modification of N-methyl-D-aspartate receptor activity and associated LTP mechanisms 2,15,16. Studies on motor learning point towards the involvement of intracortical inhibition in synaptic plasticity, as learning a motor sequence reduces GABA levels in M1, presumably through LTP 17. A recent TMS study also supports the close link between GABAB receptors and LTP as it was found that abnormal prolongation of the CSP in concussed athletes was linked to suppression of LTP plasticity 18.
The results of cathodal stimulation on intracortical inhibition are much more difficult to interpret. In contrast to most previous studies 24, cathodal tDCS failed to reduce MEP size. The absence of inhibitory effects following cathodal stimulation has been observed in several cognitive studies but more rarely in published studies of motor cortex excitability 24. Although the lack of significant results could in part be attributable to the limited statistical power of the small sample size, significant inhibitory cathodal effects on MEP size have been reported in studies with similar sample sizes 1. The absence of cathodal tDCS inhibition on corticospinal excitability suggests that the null CSP/LICI effect should be taken with caution, and further studies are needed to determine with certainty whether cathodal tDCS can reliably modulate GABAB-related intracortical inhibition.
This work was funded by the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada and the Fonds de Recherche du Québec – Santé.
There are no conflicts of interest.
1. Nitsche MA, Paulus W. Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation
. J Physiol. 2000;527:633–639
2. Liebetanz D, Nitsche MA, Tergau F, Paulus W. Pharmacological approach to the mechanisms of transcranial DC-stimulation-induced after-effects of human motor cortex excitability. Brain. 2002;125:2238–2247
3. Stagg CJ, Nitsche MA. Physiological basis of transcranial direct current stimulation
. Neuroscientist. 2011;17:37–53
4. Fritsch B, Reis J, Martinowich K, Schambra HM, Ji Y, Cohen LG, et al. Direct current stimulation promotes BDNF-dependent synaptic plasticity: potential implications for motor learning. Neuron. 2010;66:198–204
5. Di Lazzaro V, Manganelli F, Dileone M, Notturno F, Esposito M, Capasso M, et al. The effects of prolonged cathodal direct current stimulation on the excitatory and inhibitory circuits of the ipsilateral and contralateral motor cortex. J Neural Transm. 2012 , DOI: 10.1007/s00702-012-0845-4
6. Antal A, Terney D, Kühnl S, Paulus W. Anodal transcranial direct current stimulation
of the motor cortex ameliorates chronic pain and reduces short intracortical inhibition. J Pain Symptom Manage. 2010;39:890–903
7. Suzuki K, Fujiwara T, Tanaka N, Tsuji T, Masakado Y, Hase K, et al. Comparison of the after-effects of transcranial direct current stimulation
over the motor cortex in patients with stroke and healthy volunteers. Int J Neurosci. 2012;122:675–681
8. Hummel F, Celnik P, Giraux P, Floel A, Wu W-H, Gerloff C, et al. Effects of non-invasive cortical stimulation on skilled motor function in chronic stroke. Brain. 2005;128:490–499
9. Hasan A, Nitsche MA, Herrmann M, Schneider-Axmann T, Marshall L, Gruber O, et al. Impaired long-term depression in schizophrenia: a cathodal tDCS pilot study. Brain Stimul. 2012;5:475–483
10. Ziemann U, Lönnecker S, Steinhoff BJ, Paulus W. The effect of lorazepam on the motor cortical excitability in man. Exp Brain Res. 1996;109:127–135
11. McDonnell MN, Orekhov Y, Ziemann U. The role of GABAB receptors in intracortical inhibition in the human motor cortex. Exp Brain Res. 2006;173:86–93
12. Ziemann U. TMS and drugs. Clin Neurophysiol. 2004;115:1717–1729
13. Stagg CJ, Best JG, Stephenson MC, O'Shea J, Wylezinska M, Kincses ZT, et al. Polarity-sensitive modulation of cortical neurotransmitters by transcranial stimulation. J Neurosci. 2009;29:5202–5206
14. Rossini PM, Barker AT, Berardelli A, Caramia MD, Caruso G, Cracco RQ, et al. Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application. Report of an IFCN committee. Electroencephalogr Clin Neurophysiol. 1994;91:79–92
15. Reis J, Fritsch B. Modulation of motor performance and motor learning by transcranial direct current stimulation
. Curr Opin Neurol. 2011;24:590–596
16. Nitsche MA, Fricke K, Henschke U, Schlitterlau A, Liebetanz D, Lang N, et al. Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation
in humans. J Physiol. 2003;553:293–301
17. Floyer-Lea A, Wylezinska M, Kincses T, Matthews PM. Rapid modulation of GABA concentration in human sensorimotor cortex during motor learning. J Neurophysiol. 2006;95:1639–1644
18. De Beaumont L, Tremblay S, Poirier J, Lassonde M, Théoret H. Altered bidirectional plasticity and reduced implicit motor learning in concussed athletes. Cereb Cortex. 2012;22:112–121
19. Farzan F, Barr MS, Levinson AJ, Chen R, Wong W, Fitzgerald PB, et al. Reliability of long-interval cortical inhibition in healthy human subjects: a TMS-EEG study. J Neurophysiol. 2010;104:1339–1346
20. De Beaumont L, Mongeon D, Tremblay S, Messier J, Prince F, Leclerc S, et al. Persistent motor system abnormalities in formerly concussed athletes. J Athl Train. 2011;46:234–240
21. Reis J, Cohen LG, Pearl PL, Fritsch B, Jung NH, Dustin I, et al. GABAB-ergic motor cortex dysfunction in SSADH deficiency. Neurology. 2012;79:47–54
22. Inghilleri M, Berardelli A, Cruccu G, Manfredi M. Silent period evoked by transcranial stimulation of the human cortex and cervicomedullary junction. J Physiol. 1993;466:521–534
23. Werhahn KJ, Kunesch E, Noachtar S, Benecke R, Classen J. Differential effects on motorcortical inhibition induced by blockade of GABA uptake in humans. J Physiol. 1999;517:591–597
24. Jacobson L, Koslowsky M, Lavidor M. tDCS polarity effects in motor and cognitive domains: a meta-analytical review. Exp Brain Res. 2011;216:1–10