Purpose: The aim of the present study was to assess, in healthy individuals, the impact of M1-M1 tDCS on primary motor cortex excitability using transcranial magnetic stimulation and sensorimotor metabolite concentration using 1H-MRS.
Methods: For both experiments, each participant received the three following interventions (20 min tDCS, 1 mA): left-anodal/right-cathodal, left-cathodal/right-anodal, sham. The effects of tDCS were assessed via motor evoked potentials (experiment 1) and metabolite concentrations (experiment 2) immediately after and 12 minutes following the end of stimulation and compared to baseline measurement.
Results: No effect of M1-M1 tDCS on corticospinal excitability was found. Similarly, M1-M1 tDCS did not significantly modulate metabolite concentrations. High inter-subject variability was noted. Response rate analysis showed a tendency towards inhibition following left-anodal/right-cathodal tDCS in 50% of participants and increased GABA levels in 45% of participants.
Conclusion: In line with recent studies showing important inter-subject variability following M1-supraorbital tDCS, the present data show that M1-M1 stimulation is also associated with large response variability. The absence of significant effects suggests that current measures may lack sensitivity to assess changes in M1 neurophysiology and metabolism associated with M1-M1 tDCS.
BachtiarV., NearJ., Johansen-BergH., & StaggC.J. (2015). Modulation of GABA and resting state functional connectivity by transcranial direct current stimulation. eLife, 4, 1–9.
2.
BatsikadzeG., MoliadzeV., PaulusW., KuoM.F., & NitscheM.A. (2013). Partially non-linear stimulation intensity-dependent effects of direct current stimulation on motor cortex excitability in humans. Journal of Physiology, 591, 1987–2000.
3.
ChenR., ClassenJ., GerloffC., CelnikP., WassermannE.M., HallettM., & CohenL.G. (1997). Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation. Neurology, 48, 1398–1403.
4.
DarlingW.G., WolfS.L., & ButlerA.J. (2006). Variability of motor potentials evoked by transcranial magnetic stimulation depends on muscle activation. Experimental Brain Research, 174, 376–385.
5.
Di LazzaroV., DileoneM., CaponeF., PellegrinoG., RanieriF., MusumeciG., FlorioL., Di PinoG., & FregniF. (2014). Immediate and late modulation of interhemipheric imbalance with bilateral transcranial direct current stimulation in acute stroke. Brain Stimulation, 7, 841–848.
6.
Di LazzaroV., ManganelliF., DileoneM., NotturnoF., EspositoM., CapassoM., DubbiosoR., PaceM., RanieriF., MinicuciG., & SantoroL. (2012). The effects of prolonged cathodal direct current stimulation on the excitatory and inhibitory circuits of the ipsilateral and contralateral motor cortex. Journal of Neural Transmission, 119, 1499–1506.
7.
DmochowskiJ.P., DattaA., HuangY., RichardsonJ.D., BiksonM., FridrikssonJ., & ParraL.C. (2013). Targeted transcranial direct current stimulation for rehabilitation after stroke. Neuroimage, 75, 12–19.
8.
FaulF., ErdfelderE., LangA.G., & BuchnerA. (2007). G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behor Research Methods, 39, 175–191
.
9.
FerreriF., VecchioF., PonzoD., PasqualettiP., & RossiniP.M.. Time-varying coupling of EEG oscillations predicts excitability fluctuations in the primary motor cortex as reflected by motor evoked potentials amplitude: An EEG-TMS study. Human Brain Mapping (2014) 35, 1969–1980.
10.
FrickeK., SeeberA.A., ThirugnanasambandamN., PaulusW., NitscheM.A., & RothwellJ C. (2011). Time course of the induction of homeostatic plasticity generated by repeated transcranial direct current stimulation of the human motor cortex. Journal of Neurophysiology, 105, 1141–1149.
11.
FritschB., ReisJ., MartinowichK., SchambraH.M., JiY., CohenL.G., & LuB. (2010). Direct current stimulation promotes BDNF-dependent synaptic plasticity: Potential implications for motor learning. Neuron, 66, 198–204.
12.
FrocD.J., ChapmanC.A., TrepelC., & RacineR.J. (2000). Long-term depression and depotentiation in the sensorimotor cortex of the freely moving rat. Journal of Neuroscience, 20, 438–445.
13.
GasparovicC., SongT., DevierD., BockholtH.J., CaprihanA., MullinsP.G., PosseS., JungR.E., & MorrisonL.A. (2006). Use of tissue water as a concentration reference for proton spectroscopic imaging. Magnetic Resonance in Medicine, 55, 1219–1226.
14.
Gomez Palacio SchjetnanA., FarajiJ., MetzG.A., TatsunoM., & LuczakA. (2013). Transcranial direct current stimulation in stroke rehabilitation: A review of recent advancements. Stroke Research and Treatment, 2013, 170256.
15.
GovindarajuV., YoungK., & MaudsleyA.A. (2000). Proton NMR chemical shifts and coupling constants for brain metabolites. NMR in Biomedicine, 13, 129–153.
16.
GruetterR., & TkácI. (2000). Field mapping without reference scan using asymmetric echo-planar techniques. Magnetic Resonance in Medicine, 43, 319–323.
17.
HanleyJ.A., NegassaA., & ForresterJ.E. (2003). Statistical analysis of correlated data using generalized estimating equations: An orientation. American Journal of Epidemiology, 157, 364–375.
18.
HamadaM., MuraseN., HasanA., BalaratnamM., & RothwellJ.C. (2013). The role of interneuron networks in driving human motor cortical plasticity. Cerebral cortex, 23, 1593–1605.
19.
HenryP.-G., MarjanskaM., WallsJ.D., ValetteJ., GruetterR., & UgurbilK. (2006). Proton-observed carbon-edited NMR spectroscopy in strongly coupled second-order spin systems. Magnetic Resonance in Medicine, 55, 250–257.
20.
Hone-BlanchetA., EddenR.A., & FecteauS. (2016). Online effects of transcranial direct current stimulation in real time on human prefrontal and striatal metabolites. Biological Psychiatry, doi: 10.1016/j.biopsych.2015.11.008.
21.
HorvathJ.C., CarterO., & ForteJ.D. (2014). Transcranial direct current stimulation: Five important issues we aren’t discussing (but probably should be. Frontiers in Systems Neuroscience, 8, 1–8.
22.
HorvathJ.C., ForteJ.D., & CarterO. (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.
23.
HummelF.C., & CohenL.G. (2006). Non-invasive brain stimulation: A new strategy to improve neurorehabilitation after stroke?Lancet Neurology, 5, 708–712.
24.
JacobsonL., KoslowskyM., & LavidorM. (2011). tDCS polarity effects in motor and cognitive domains: A meta-analytical review. Experimental Brain Research, 216, 1–10.
25.
KidgellD.J., GoodwillA.M., FrazerA.K., & DalyR.M. (2013). Induction of cortical plasticity and improved motor performance following unilateral and bilateral transcranial direct current stimulation of the primary motor cortex. BMC Neuroscience, 14, 64.
26.
KiersL., CrosD., ChiappaK.H., & FangJ. (1993). Variability of motor potentials evoked by transcranial magnetic stimulation. Electroencephalogry and Clinical Neurophysiolology, 89, 415–423.
27.
KimS., StephensonM.C., MorrisP.G., & JacksonS.R. (2014). tDCS-induced alterations in GABA concentration within primary motor cortex predict motor learning and motor memory: A 7 T magnetic resonance spectroscopy study. Neuroimage, 99, 237–243.
28.
KloseU. (1990). In vivo proton spectroscopy in presence of eddy currents. Magnetic Resonance in Medicine, 14, 26–30.
29.
KrauseB. (2013). The effect of transcranial direct current stimulation: A role for cortical excitation/inhibition balance?Frontiers in human neuroscience, 7, 1–4.
30.
KreisR. (2015). The trouble with quality filtering based on relative cramér-rao lower bounds. Magnetic Resonance in Medicine, 75, 15–18.
31.
LangN., SiebnerH.R., WardN.S., LeeL., NitscheM.A., PaulusW., RothwellJ.C., LemonR.N., & FrackowiakR.S. (2005). How does transcranial DC stimulation of the primary motor cortex alter regional neuronal activity in the human brain?European Journal of Neuroscience, 22, 495–504.
32.
LepageJ.-F., ClouchouxC., LassondeM., EvansA.C., DealC.L., & ThéoretH. (2011). Abnormal motor cortex excitability is associated with reduced cortical thickness in X monosomy. Human Brain Mapping, 34, 936–944.
33.
LiebetanzD., NitscheM.A., TergauF., & PaulusW. (2002). Pharmacological approach to the mechanisms of transcranial DC-stimulation-induced after-effects of human motor cortex excitability. Brain, 125, 2238–2247.
34.
LindenbergR., NachtigallL., MeinzerM., SiegM.M., & FloelA. (2013). Differential effects of dual and unihemispheric motor cortex stimulation in older adults. Journal of Neuroscience, 33, 9176–9183.
35.
López-AlonsoV., CheeranB., Río-RodríguezD., & Fernández-del-OlmoM. (2014). Inter-individual Variability in Response to Non-invasive Brain Stimulation Paradigms. Brain Stimulation, 7, 372–380.
36.
McConnellK.A., NahasZ., ShastriA., LorberbaumJ.P., KozelF.A., BohningD.E., & GeorgeM.S. (2001). The transcranial magnetic stimulation motor threshold depends on the distance from coil to underlying cortex: A replication in healthy adults comparing two methods of assessing the distance to cortex. Biolological Psychiatry, 49, 454–459.
37.
MescherM., MerkleH., KirschJ., GarwoodM., & GruetterR. (1998). Simultaneous in vivo spectral editing and water suppression. NMR Biomedicine, 11, 266–272.
38.
Mordillo-MateosL., Turpin-FenollL., Millán-PascualJ., Núñez-PérezN., PanyavinI., Gómez-ArgüellesJ.M., Botia-PaniaguaE., FoffaniG., LangN., & OlivieroA. (2012). Effects of simultaneous bilateral tDCS of the human motor cortex. Brain Stimulation, 5, 214–222.
39.
MuraseN., DuqueJ., MazzocchioR., & CohenL.G. (2004). Influence of interhemispheric interactions on motor function in chronic stroke. Annals of Neurology, 55, 400–409.
40.
NitscheM.A., CohenL.G., WassermannE.M., PrioriA., LangN., AntalA., PaulusW., HummelF., BoggioP.S., FregniF., & Pascual-LeoneA. (2008). Transcranial direct current stimulation: State of the art 2008. Brain Stimulation, 1, 206–223.
41.
O’GormanR.L., MichelsL., EddenR.A., MurdochJ.B., & MartinE. (2011). in vivo detection of GABA and glutamate with MEGA-PRESS: Reproducibility and gender effects. Journal of Magnetic Resonance Imaging, 33, 1262–1267.
42.
O’SheaJ., BoudriasM.-H., StaggC.J., BachtiarV., KischkaU., BlicherJ.U., & Johansen-BergH. (2013). Predicting behavioural response to TDCS in chronic motor stroke. Neuroimage, 15, 924–933
.
43.
PitcherJ.B., OgstonK.M., & MilesT.S. (2003). Age and sex differences in human motor cortex input-output characteristics. Journal of Physiology, 546, 605–613.
44.
ProvencherS.W. (1993). Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magnetic Resonance in Medicine, 30, 672–679.
45.
ProvencherS.W. (2001). Automatic quantitation of localized in vivo 1H spectra with LCModel. NMR Biomedicine, 14, 260–264.
46.
RooneyW.D., JohnsonG., LiX., CohenE.R., KimS.G., UgurbilK., & SpringerC.S. (2007). Magnetic field and tissue dependencies of human brain longitudinal 1H2O relaxation in vivo. Magnetic Resonance in Medicine, 57, 308–318.
47.
RossiS., HallettM., RossiniP.M., Pascual-LeoneA., & Safety of TMS Consensus Group. (2009). Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clinical Neurophysiology, 120, 2008–2039.
48.
RossiniP.M., BurkeD., ChenR., CohenL.G., DaskalakisZ., Di IorioR., Di LazzaroV., FerreriF., FitzgeraldP.B., GeorgeM.S., & ZiemannU. (2015). Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an IFCN Committee. Clinical Neurophysiology, 126, 1071–1107
.
SehmB., KippingJ., SchäferA., VillringerA., & RagertP. (2013). A comparison between uni- and bilateral tdcs effects on functional connectivity of the human motor cortex. Frontiers in Human Neuroscience, 7, 183.
51.
SilvantoJ., MuggletonN., & WalshV. (2008). State-dependency in brain stimulation studies of perception and cognition. Trends in Cognitive Science, 12, 447–454.
52.
SimeoniS., HannahR., SatoD., KawakamiM., RothwellJ.C., & GigliG.L. (2015). Effects of Quadripulse Stimulation on Human Motor Cortex Excitability: A Replication Study. Brain Stimulation, 9, 148–50.
53.
StaggC.J., BachtiarV., & Johansen-BergH. (2011). The role of GABA in human motor learning. Current Biology, 21, 480–484.
54.
StaggC.J., BestJ.G., StephensonM.C., O’SheaJ., WylezinskaM., KincsesZ.T., MorrisP.G., MatthewsP.M., & Johansen-BergH. (2009). Polarity-sensitive modulation of cortical neurotransmitters by transcranial stimulation. Journal of Neuroscience, 29, 5202–5206.
55.
StaggC.J., & NitscheM.A. (2011). Physiological basis of transcranial direct current stimulation. Neuroscientist, 17, 37–53.
56.
StrubeW., BunseT., MalchowB., & HasanA. (2015). Efficacy and interindividual variability in motor-cortex plasticity following anodal tdcs and paired-associative stimulation. Neural Plasticity, 2015, 530423.
57.
TazoeT., EndohT., KitamuraT., & OgataT. (2014). Polarity specific effects of transcranial direct current stimulation on interhemispheric inhibition. PloS One, 9, e114244.
58.
TremblayS., BeauléV., LepageJ.F., & ThéoretH. (2013). Anodal transcranial direct current stimulation modulates GABAB-related intracortical inhibition in the M1 of healthy individuals. Neuroreport, 24, 46–50.
59.
TremblayS., BeauléV., ProulxS., LafleurL.-P., DoyonJ., MarjańskaM., & ThéoretH. (2014b). The use of magnetic resonance spectroscopy as a tool for the measurement of bi-hemispheric transcranial electric stimulation effects on primary motor cortex metabolism. Journal of Visualized Experiment, 93, e51631.
60.
TremblayS., LepageJ.F., Latulipe-LoiselleA., FregniF., Pascual-LeoneA., & ThéoretH. (2014a). The uncertain outcome of prefrontal tDCS. Brain Stimulation, 7, 773–783.
61.
TrepelC., & RacineR.J. (2000). GABAergic modulation of neocortical long-term potentiation in the freely moving rat. Synapse, 35, 120–128.
62.
VallenceA.M., GoldsworthyM.R., HodylN.A., SemmlerJ.G., PitcherJ.B., & RiddingM.C. (2015). Inter- and intra-subject variability of motor cortex plasticity following continuous theta-burst stimulation. Neuroscience, 304, 266–278.
63.
VinesB.W., CerrutiC., & SchlaugG. (2008). Dual-hemisphere tDCS facilitates greater improvements for healthy subjects’ non-dominant hand compared to uni-hemisphere stimulation. BMC Neuroscience, 9, 103–.
64.
WansapuraJ.P., HollandS.K., DunnR.S., & BallW.S. (1999). NMR relaxation times in the human brain at 3.0 tesla. Journal of Magnetic Resonance Imaging, 9, 531–538.
65.
WiethoffS., HamadaM., & RothwellJ.C. (2014). Variability in response to transcranial direct current stimulation of the motor cortex. Brain Stimulation, 7, 468–475.
66.
XuJ., HealyS.M., TruongD.Q., DattaA., BiksonM., & PotenzaM.N. (2015). A feasibility study of bilateral anodal stimulation of the prefrontal cortex using high-definition electrodes in healthy participants. Yale Journal of Biology and Medicine, 88, 219–225.
67.
YousryT.A., SchmidU.D., AlkadhiH., SchmidtD., PeraudA., BuettnerA., & WinklerP. (1997). Localization of the motor hand area to a knob on the precentral gyrus. A new landmark. Brain, 120, 141–157.
