Efficacy of tRNS and 140 Hz tACS on motor cortex excitability seemingly dependent on sensitivity to sham stimulation

Kortuem, Viktoria; Kadish, Navah Ester; Siniatchkin, Michael; Moliadze, Vera

doi:10.1007/s00221-019-05640-w

Research Article
Published: 03 September 2019

Efficacy of tRNS and 140 Hz tACS on motor cortex excitability seemingly dependent on sensitivity to sham stimulation

Viktoria Kortuem¹,
Navah Ester Kadish¹,
Michael Siniatchkin^1,2 &
Vera Moliadze¹

Experimental Brain Research volume 237, pages 2885–2895 (2019)Cite this article

529 Accesses
4 Citations
1 Altmetric
Metrics details

Abstract

This study investigates the effect of corticospinal excitability during sham stimulation on the individual response to transcranial non-invasive brain stimulation (tNIBS). Thirty healthy young adults aged 24.2 ± 2.8 S.D. participated in the study. Sham, as well as 1 mA of tRNS and 140 Hz tACS stimulation were applied for 10 min each at different sessions. The effect of each stimulation type was quantified by recording TMS-induced, motor evoked potentials (MEPs) before (baseline) and at fixed time points after stimulation (T0, T30, T60 min.). According to the individual response to sham stimulation at T0 in comparison to baseline MEPs, subjects were regarded as responder or non-responder to sham. Following, MEPs at T0, T30 and T60 after verum or sham stimulation were assessed with a repeated measures ANOVA with the within-subject factor stimulation (sham, tRNS, 140 Hz tACS) and the between-subjects factor group (responder vs non-responder). We found that individuals who did not show immediately changes in excitability in sham stimulation sessions were the ones who responded to active stimulation conditions. On the other hand, individuals who responded to sham condition, by either increases or decreases in MEPS, did not respond to active verum stimulation. This result suggests that the presence or lack of responses to sham stimulation can provide a marker for how individuals will respond to tRNS/tACS and thus provide an explanation for the variability in interindividual response. The results of this study draw attention to the general reactivity of the brain, which can be taken into account when planning future studies using tNIBS.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price includes VAT (Canada)

References

Ambrus GG, Pisoni A, Primassin A, Turi Z, Paulus W, Antal A (2015) Bi-frontal transcranial alternating current stimulation in the ripple range reduced overnight forgetting. Front Cell Neurosci 9:374. https://doi.org/10.3389/fncel.2015.00374
Article PubMed PubMed Central Google Scholar
Ammann C, Lindquist MA, Celnik PA (2017) Response variability of different anodal transcranial direct current stimulation intensities across multiple sessions. Brain Stimul 10:757–763. https://doi.org/10.1016/j.brs.2017.04.003
Article PubMed PubMed Central Google Scholar
Antal A, Herrmann CS (2016) Transcranial alternating current and random noise stimulation: possible mechanisms. Neural Plast 2016:3616807. https://doi.org/10.1155/2016/3616807
CAS Article PubMed PubMed Central Google Scholar
Antal A, Terney D, Poreisz C, Paulus W (2007) Towards unravelling task-related modulations of neuroplastic changes induced in the human motor cortex. Eur J Neurosci 26:2687–2691. https://doi.org/10.1111/j.1460-9568.2007.05896.x
Article PubMed Google Scholar
Antal A, Chaieb L, Moliadze V et al (2010) Brain-derived neurotrophic factor (BDNF) gene polymorphisms shape cortical plasticity in humans. Brain Stimul 3:230–237. https://doi.org/10.1016/j.brs.2009.12.003
Article PubMed Google Scholar
Batsikadze G, Moliadze V, Paulus W, Kuo MF, Nitsche M (2013) Partially non-linear stimulation intensity-dependent effects of direct current stimulation on motor cortex excitability in humans. J Physiol 591:1987–2000
CAS Article PubMed PubMed Central Google Scholar
Bienenstock EL, Cooper LN, Munro PW (1982) Theory for the development of neuron selectivity: orientation specificity and binocular interaction in visual cortex. J Neurosci 2:32–48
CAS Article PubMed PubMed Central Google Scholar
Bocci T, Caleo M, Tognazzi S et al (2014) Evidence for metaplasticity in the human visual cortex. J Neural Transm (Vienna) 121:221–231. https://doi.org/10.1007/s00702-013-1104-z
Article Google Scholar
Brauer H, Kadish NE, Pedersen A, Siniatchkin M, Moliadze V (2018) No modulatory effects when stimulating the right inferior frontal gyrus with continuous 6 Hz tACS and tRNS on response inhibition: a behavioral study. Neural Plast 2018:3156796. https://doi.org/10.1155/2018/3156796
Article PubMed PubMed Central Google Scholar
Brignani D, Ruzzoli M, Mauri P, Miniussi C (2013) Is transcranial alternating current stimulation effective in modulating brain oscillations? PLoS One 8:e56589. https://doi.org/10.1371/journal.pone.0056589
CAS Article PubMed PubMed Central Google Scholar
Cabral-Calderin Y, Williams KA, Opitz A, Dechent P, Wilke M (2016) Transcranial alternating current stimulation modulates spontaneous low frequency fluctuations as measured with fMRI. Neuroimage 141:88–107. https://doi.org/10.1016/j.neuroimage.2016.07.005
Article PubMed Google Scholar
Chew T, Ho KA, Loo CK (2015) Inter- and intra-individual variability in response to transcranial direct current stimulation (tDCS) at varying current intensities. Brain Stimul 8:1130–1137. https://doi.org/10.1016/j.brs.2015.07.031
Article PubMed Google Scholar
Dissanayaka TD, Zoghi M, Farrell M, Egan GF, Jaberzadeh S (2018) Sham transcranial electrical stimulation and its effects on corticospinal excitability: a systematic review and meta-analysis. Rev Neurosci 29:223–232. https://doi.org/10.1515/revneuro-2017-0026
Article PubMed Google Scholar
Faul F, Erdfelder E, Lang A-G, Buchner A (2007) G* Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 39:175–191
Article PubMed Google Scholar
Fertonani A, Miniussi C (2016) Transcranial electrical stimulation: what we know and do not know about mechanisms. Neuroscientist. https://doi.org/10.1177/1073858416631966
Article PubMed PubMed Central Google Scholar
Fertonani A, Pirulli C, Miniussi C (2011) Random noise stimulation improves neuroplasticity in perceptual learning. J Neurosci 31:15416–15423. https://doi.org/10.1523/jneurosci.2002-11.2011
CAS Article PubMed PubMed Central Google Scholar
Feurra M, Pasqualetti P, Bianco G, Santarnecchi E, Rossi A, Rossi S (2013) State-dependent effects of transcranial oscillatory currents on the motor system: what you think matters. J Neurosci 33:17483–17489. https://doi.org/10.1523/jneurosci.1414-13.2013
CAS Article PubMed PubMed Central Google Scholar
Fierro B, Brighina F, Vitello G et al (2005) Modulatory effects of low- and high-frequency repetitive transcranial magnetic stimulation on visual cortex of healthy subjects undergoing light deprivation. J Physiol 565:659–665. https://doi.org/10.1113/jphysiol.2004.080184
CAS Article PubMed PubMed Central Google Scholar
Fonteneau C, Mondino M, Arns M et al (2019) Sham tDCS: a hidden source of variability? Reflections for further blinded, controlled trials. Brain Stimul 12:668–673. https://doi.org/10.1016/j.brs.2018.12.977
Article PubMed Google Scholar
Furubayashi T, Terao Y, Arai N et al (2008) Short and long duration transcranial direct current stimulation (tDCS) over the human hand motor area. Exp Brain Res 185:279–286. https://doi.org/10.1007/s00221-007-1149-z
Article PubMed Google Scholar
Guerra A, Lopez-Alonso V, Cheeran B, Suppa A (2017) Variability in non-invasive brain stimulation studies: reasons and results. Neurosci Lett. https://doi.org/10.1016/j.neulet.2017.12.058
Article PubMed Google Scholar
Hamada M, Murase N, Hasan A, Balaratnam M, Rothwell JC (2013) The role of interneuron networks in driving human motor cortical plasticity. Cereb Cortex 23:1593–1605. https://doi.org/10.1093/cercor/bhs147
Article PubMed Google Scholar
Hordacre B, Goldsworthy MR, Vallence AM et al (2016) Variability in neural excitability and plasticity induction in the human cortex: a brain stimulation study. Brain Stimul. https://doi.org/10.1016/j.brs.2016.12.001
Article PubMed Google Scholar
Hordacre B, Moezzi B, Ridding MC (2018) Neuroplasticity and network connectivity of the motor cortex following stroke: a transcranial direct current stimulation study. Hum Brain Mapp 39:3326–3339. https://doi.org/10.1002/hbm.24079
Article PubMed PubMed Central Google Scholar
Horvath JC, Carter O, Forte JD (2014) Transcranial direct current stimulation: five important issues we aren’t discussing (but probably should be). Front Syst Neurosci 8:2
Article PubMed PubMed Central Google Scholar
Horvath JC, Forte JD, Carter O (2015) Evidence that transcranial direct current stimulation (tDCS) generates little-to-no reliable neurophysiologic effect beyond MEP amplitude modulation in healthy human subjects: a systematic review. Neuropsychologia 66:213–236
Article PubMed Google Scholar
Horvath JC, Vogrin SJ, Carter O, Cook MJ, Forte JD (2016) Effects of a common transcranial direct current stimulation (tDCS) protocol on motor evoked potentials found to be highly variable within individuals over 9 testing sessions. Exp Brain Res 234(9):2629–2642. https://doi.org/10.1007/s00221-016-4667-8
Article PubMed Google Scholar
Javadi AH, Cheng P, Walsh V (2012) Short duration transcranial direct current stimulation (tDCS) modulates verbal memory. Brain Stimul 5:468–474. https://doi.org/10.1016/j.brs.2011.08.003
Article PubMed Google Scholar
Kanai R, Paulus W, Walsh V (2010) Transcranial alternating current stimulation (tACS) modulates cortical excitability as assessed by TMS-induced phosphene thresholds. Clin Neurophysiol 121:1551–1554. https://doi.org/10.1016/j.clinph.2010.03.022
Article PubMed Google Scholar
Karabanov A, Ziemann U, Hamada M et al (2015) Consensus paper: probing homeostatic plasticity of human cortex with non-invasive transcranial brain stimulation. Brain Stimul 8:442–454. https://doi.org/10.1016/j.brs.2015.01.404
Article PubMed Google Scholar
Krause B, Cohen Kadosh R (2014) Not all brains are created equal: the relevance of individual differences in responsiveness to transcranial electrical stimulation. Front Syst Neurosci 8:25
PubMed PubMed Central Google Scholar
Labruna L, Jamil A, Fresnoza S et al (2016) Efficacy of anodal transcranial direct current stimulation is related to sensitivity to transcranial magnetic stimulation. Brain Stimul 9:8–15. https://doi.org/10.1016/j.brs.2015.08.014
Article PubMed Google Scholar
Lang N, Nitsche MA, Paulus W, Rothwell JC, Lemon RN (2004) Effects of transcranial direct current stimulation over the human motor cortex on corticospinal and transcallosal excitability. Exp Brain Res 156:439–443. https://doi.org/10.1007/s00221-003-1800-2
CAS Article PubMed Google Scholar
Li LM, Uehara K, Hanakawa T (2015) The contribution of interindividual factors to variability of response in transcranial direct current stimulation studies. Front Cell Neurosci. https://doi.org/10.3389/fncel.2015.00181
Article PubMed PubMed Central Google Scholar
López-Alonso V, Cheeran B, Río-Rodríguez D, Fernández-del-Olmo M (2014) Inter-individual variability in response to non-invasive brain stimulation paradigms. Brain Stimul 7:372–380
Article PubMed Google Scholar
Mehta AR, Pogosyan A, Brown P, Brittain JS (2015) Montage matters: the influence of transcranial alternating current stimulation on human physiological tremor. Brain Stimul 8:260–268. https://doi.org/10.1016/j.brs.2014.11.003
Article PubMed PubMed Central Google Scholar
Mei F, Nagappan G, Ke Y, Sacktor TC, Lu B (2011) BDNF facilitates L-LTP maintenance in the absence of protein synthesis through PKMzeta. PLoS One 6:e21568. https://doi.org/10.1371/journal.pone.0021568
CAS Article PubMed PubMed Central Google Scholar
Miniussi C, Harris JA, Ruzzoli M (2013) Modelling non-invasive brain stimulation in cognitive neuroscience. Neurosci Biobehav Rev 37:1702–1712. https://doi.org/10.1016/j.neubiorev.2013.06.014
Article PubMed Google Scholar
Moliadze V, Antal A, Paulus W (2010a) Boosting brain excitability by transcranial high frequency stimulation in the ripple range. J Physiol 588:4891–4904. https://doi.org/10.1113/jphysiol.2010.196998 (jphysiol.2010.196998 [pii])
CAS Article PubMed PubMed Central Google Scholar
Moliadze V, Antal A, Paulus W (2010b) Electrode-distance dependent after-effects of transcranial direct and random noise stimulation with extracephalic reference electrodes. Clin Neurophysiol 121:2165–2171. https://doi.org/10.1016/j.clinph.2010.04.033 (S1388-2457(10)00481-5 [pii])
Article PubMed Google Scholar
Moliadze V, Atalay D, Antal A, Paulus W (2012) Close to threshold transcranial electrical stimulation preferentially activates inhibitory networks before switching to excitation with higher intensities. Brain Stimul 5:505–511. https://doi.org/10.1016/j.brs.2011.11.004 (S1935-861X(11)00167-7 [pii])
Article PubMed Google Scholar
Moliadze V, Schmanke T, Andreas S, Lyzhko E, Freitag CM, Siniatchkin M (2015) Stimulation intensities of transcranial direct current stimulation have to be adjusted in children and adolescents. Clin Neurophysiol 126:1392–1399. https://doi.org/10.1016/j.clinph.2014.10.142
Article PubMed Google Scholar
Moliadze V, Lyzhko E, Schmanke T, Andreas S, Freitag CM, Siniatchkin M (2018) 1 mA cathodal tDCS shows excitatory effects in children and adolescents: insights from TMS evoked N100 potential. Brain Res Bull 140:43–51. https://doi.org/10.1016/j.brainresbull.2018.03.018
Article PubMed Google Scholar
Moliadze V, Sierau L, Lyzhko E, Stenner T, Werchowski M, Siniatchkin M, Hartwigsen G (2019) After-effects of 10 Hz tACS over the prefrontal cortex on phonological word decisions. Brain Stimul. https://doi.org/10.1016/j.brs.2019.06.021
Article PubMed Google Scholar
Muller-Dahlhaus F, Ziemann U (2015) Metaplasticity in human cortex. Neuroscientist 21:185–202. https://doi.org/10.1177/1073858414526645
CAS Article PubMed Google Scholar
Nguyen J, Deng Y, Reinhart RMG (2018) Brain-state determines learning improvements after transcranial alternating-current stimulation to frontal cortex. Brain Stimul. https://doi.org/10.1016/j.brs.2018.02.008
Article PubMed PubMed Central Google Scholar
Nitsche MA, Paulus W (2000) Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol 527(Pt 3):633–639. doi: PHY_1055 [pii]
Oldfield RC (1971) The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9:97–113
CAS Article PubMed Google Scholar
Paulus W (2011) Transcranial electrical stimulation (tES–tDCS; tRNS, tACS) methods. Neuropsychological rehabilitation 21:602–617
Article PubMed Google Scholar
Paulus W, Nitsche MA, Antal A (2016) Application of transcranial electric stimulation (tDCS, tACS, tRNS). Eur Psychol 21(1):4–14
Article Google Scholar
Pirulli C, Fertonani A, Miniussi C (2013) The role of timing in the induction of neuromodulation in perceptual learning by transcranial electric stimulation. Brain Stimul 6:683–689. https://doi.org/10.1016/j.brs.2012.12.005
Article PubMed Google Scholar
Poreisz C, Boros K, Antal A, Paulus W (2007) Safety aspects of transcranial direct current stimulation concerning healthy subjects and patients. Brain Res Bull 72:208–214
Article PubMed Google Scholar
Ridding M, Ziemann U (2010) Determinants of the induction of cortical plasticity by non-invasive brain stimulation in healthy subjects. J Physiol 588:2291–2304
CAS Article PubMed PubMed Central Google Scholar
Ruzzoli M, Marzi CA, Miniussi C (2010) The neural mechanisms of the effects of transcranial magnetic stimulation on perception. J Neurophysiol 103:2982–2989. https://doi.org/10.1152/jn.01096.2009
Article PubMed Google Scholar
Scheldrup M, Greenwood PM, McKendrick R et al (2014) Transcranial direct current stimulation facilitates cognitive multi-task performance differentially depending on anode location and subtask. Front Hum Neurosci 8:665. https://doi.org/10.3389/fnhum.2014.00665
Article PubMed PubMed Central Google Scholar
Schinder AF, Poo M (2000) The neurotrophin hypothesis for synaptic plasticity. Trends Neurosci 23:639–645
CAS Article PubMed Google Scholar
Sehm B, Kipping J, Schafer A, Villringer A, Ragert P (2013) A comparison between uni- and bilateral tDCS effects on functional connectivity of the human motor cortex. Front Hum Neurosci 7:183. https://doi.org/10.3389/fnhum.2013.00183
Article PubMed PubMed Central Google Scholar
Siebner HR, Lang N, Rizzo V, Nitsche MA, Paulus W, Lemon RN, Rothwell JC (2004) Preconditioning of low-frequency repetitive transcranial magnetic stimulation with transcranial direct current stimulation: evidence for homeostatic plasticity in the human motor cortex. J Neurosci 24:3379–3385. https://doi.org/10.1523/jneurosci.5316-03.2004
CAS Article PubMed PubMed Central Google Scholar
Silvanto J, Muggleton N, Walsh V (2008) State-dependency in brain stimulation studies of perception and cognition. Trends Cogn Sci 12:447–454. https://doi.org/10.1016/j.tics.2008.09.004
Article PubMed Google Scholar
Stagg CJ, Nitsche MA (2011) Physiological basis of transcranial direct current stimulation. Neuroscientist 17:37–53. https://doi.org/10.1177/1073858410386614
Article PubMed Google Scholar
Teo F, Hoy KE, Daskalakis ZJ, Fitzgerald PB (2011) Investigating the role of current strength in tDCS modulation of working memory performance in healthy controls. Front Psychiatry 2:45. https://doi.org/10.3389/fpsyt.2011.00045
Article PubMed PubMed Central Google Scholar
Terney D, Chaieb L, Moliadze V, Antal A, Paulus W (2008) Increasing human brain excitability by transcranial high-frequency random noise stimulation. J Neurosci 28:14147–14155. https://doi.org/10.1523/jneurosci.4248-08.2008 (28/52/14147 [pii])
CAS Article PubMed PubMed Central Google Scholar
Tremblay S, Larochelle-Brunet F, Lafleur LP, El Mouderrib S, Lepage JF, Theoret H (2016) Systematic assessment of duration and intensity of anodal transcranial direct current stimulation on primary motor cortex excitability. Eur J Neurosci 44:2184–2190. https://doi.org/10.1111/ejn.13321
Article PubMed Google Scholar
Turi Z, Mittner M, Paulus W, Antal A (2017) Placebo intervention enhances reward learning in healthy individuals. Sci Rep 7:41028. https://doi.org/10.1038/srep41028
CAS Article PubMed PubMed Central Google Scholar
Wach C, Krause V, Moliadze V, Paulus W, Schnitzler A, Pollok B (2013) Effects of 10 Hz and 20 Hz transcranial alternating current stimulation (tACS) on motor functions and motor cortical excitability. Behav Brain Res 241:1–6. https://doi.org/10.1016/j.bbr.2012.11.038 (S0166-4328(12)00768-1 [pii])
CAS Article PubMed Google Scholar
Wiethoff S, Hamada M, Rothwell JC (2014) Variability in response to transcranial direct current stimulation of the motor cortex. Brain Stimul 7:468–475. https://doi.org/10.1016/j.brs.2014.02.003
Article PubMed Google Scholar
Ziemann U, Paulus W, Nitsche MA et al (2008) Consensus: motor cortex plasticity protocols. Brain Stimul 1:164–182. https://doi.org/10.1016/j.brs.2008.06.006
Article PubMed Google Scholar

Download references

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

Institute of Medical Psychology and Medical Sociology, University Medical Center Schleswig Holstein, Kiel University, Preußerstraße 1-9, 24105, Kiel, Germany
Viktoria Kortuem, Navah Ester Kadish, Michael Siniatchkin & Vera Moliadze
Clinic for Child and Adolescent Psychiatry, Hospital Bethel, Remterweg 13a, 33617, Bielefeld, Germany
Michael Siniatchkin

Authors

Viktoria Kortuem
View author publications
You can also search for this author in PubMed Google Scholar
Navah Ester Kadish
View author publications
You can also search for this author in PubMed Google Scholar
Michael Siniatchkin
View author publications
You can also search for this author in PubMed Google Scholar
Vera Moliadze
View author publications
You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vera Moliadze.

Ethics declarations

Conflict of interest

The authors declare that there is no conflict of interests regarding the publication of this paper. All the authors have read the manuscript and have approved this submission.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kortuem, V., Kadish, N.E., Siniatchkin, M. et al. Efficacy of tRNS and 140 Hz tACS on motor cortex excitability seemingly dependent on sensitivity to sham stimulation. Exp Brain Res 237, 2885–2895 (2019). https://doi.org/10.1007/s00221-019-05640-w

Download citation

Received: 01 December 2018
Accepted: 27 August 2019
Published: 03 September 2019
Issue Date: November 2019
DOI: https://doi.org/10.1007/s00221-019-05640-w

Keywords

Sham stimulation
tRNS
140 tACS
Plasticity
MEP