Impact of Transcranial Direct Current Stimulation (tDCS) on Neuronal Functions

Suman Das, Peter Holland, Maarten A Frens, Opher Donchin, Suman Das, Peter Holland, Maarten A Frens, Opher Donchin

Abstract

Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique, modulates neuronal excitability by the application of a small electrical current. The low cost and ease of the technique has driven interest in potential clinical applications. However, outcomes are highly sensitive to stimulation parameters, leading to difficulty maximizing the technique's effectiveness. Although reversing the polarity of stimulation often causes opposite effects, this is not always the case. Effective clinical application will require an understanding of how tDCS works; how it modulates a neuron; how it affects the local network; and how it alters inter-network signaling. We have summarized what is known regarding the mechanisms of tDCS from sub-cellular processing to circuit level communication with a particular focus on what can be learned from the polarity specificity of the effects.

Keywords: neuromodulators; neurotransmitters; oscillation; plasticity; tDCS.

Figures

Figure 1
Figure 1
The modulatory effects of tDCS from subcellular processing to the circuit level communication.

References

    1. Antal A., Varga E. T., Kincses T. Z., Nitsche M. A., Paulus W. (2004). Oscillatory brain activity and transcranial direct current stimulation in humans. Neuroreport 15, 1307–1310. 10.1097/01.wnr.0000127460.08361.84
    1. Benninger D. H., Lomarev M., Lopez G., Wassermann E. M., Li X., Considine E., et al. . (2010). Transcranial direct current stimulation for the treatment of Parkinson's disease. J. Neurol. Neurosurg. Psychiatr. 81, 1105–1111. 10.1136/jnnp.2009.202556
    1. Bikson M., Grossman P., Thomas C., Zannou A. L., Jiang J., Adnan T., et al. . (2016). Safety of transcranial direct current stimulation: evidence based update 2016. Brain Stimul. 9, 641–661. 10.1016/j.brs.2016.06.004
    1. Bikson M., Inoue M., Akiyama H., Deans J. K., Fox J. E., Miyakawa H., et al. . (2004). Effects of uniform extracellular DC electric fields on excitability in rat hippocampal slices in vitro. J. Physiol. 557, 175–190. 10.1113/jphysiol.2003.055772
    1. Bindman L. J., Lippold O. C., Redfearn J. W. (1964). THE action of brief polarizing currents on the cerebral cortex of the rat (1) during current flow and (2) in the production of long-lasting after-effects. J. Physiol. 172, 369–382.
    1. Blumberger D. M., Hsu J. H., Daskalakis Z. J. (2015). A Review of brain stimulation treatments for late-life depression. Curr. Treat Options Psychiatry 2, 413–421. 10.1007/s40501-015-0059-0
    1. Boggio P. S., Khoury L. P., Martins D. C. S., Martins O. E. M. S., de Macedo E. C., Fregni F. (2009). Temporal cortex direct current stimulation enhances performance on a visual recognition memory task in Alzheimer disease. J. Neurol. Neurosurg. Psychiatr. 80, 444–447. 10.1136/jnnp.2007.141853
    1. Brunelin J., Mondino M., Haesebaert F., Saoud M., Suaud-Chagny M. F., Poulet E. (2012). Efficacy and safety of bifocal tDCS as an interventional treatment for refractory schizophrenia. Brain Stimul. 5, 431–432. 10.1016/j.brs.2011.03.010
    1. Brunoni A. R., Kemp A. H., Shiozawa P., Cordeiro Q., Valiengo L. C. L., Goulart A. C., et al. . (2013). Impact of 5-HTTLPR and BDNF polymorphisms on response to sertraline versus transcranial direct current stimulation: implications for the serotonergic system. Eur. Neuropsychopharmacol. 23, 1530–1540. 10.1016/j.euroneuro.2013.03.009
    1. Buzsáki G., Watson B. O. (2012). Brain rhythms and neural syntax: implications for efficient coding of cognitive content and neuropsychiatric disease. Dialogues Clin. Neurosci. 14, 345–367.
    1. Castro J. B., Urban N. N. (2009). Subthreshold glutamate release from mitral cell dendrites. J. Neurosci. 29, 7023–7030. 10.1523/JNEUROSCI.5606-08.2009
    1. Chan C. Y., Hounsgaard J., Nicholson C. (1988). Effects of electric fields on transmembrane potential and excitability of turtle cerebellar Purkinje cells in vitro. J. Physiol. 402, 751–771.
    1. Chan C. Y., Nicholson C. (1986). Modulation by applied electric fields of Purkinje and stellate cell activity in the isolated turtle cerebellum. J. Physiol. 371, 89–114.
    1. Christie J. M., Chiu D. N., Jahr C. E. (2011). Ca2+-dependent enhancement of release by subthreshold somatic depolarization. Nat. Neurosci. 14, 62–68. 10.1038/nn.2718
    1. Csercsa R., Dombovári B., Fabó D., Wittner L., Erőss L., Entz L., et al. . (2010). Laminar analysis of slow wave activity in humans. Brain 133, 2814–2829. 10.1093/brain/awq169
    1. Dubljević V., Saigle V., Racine E. (2014). The rising tide of tDCS in the media and academic literature. Neuron 82, 731–736. 10.1016/j.neuron.2014.05.003
    1. Dunlop K., Hanlon C. A., Downar J. (2016). Non-invasive brain stimulation treatments for addiction and major depression. Ann. N. Y. Acad. Sci. 10.1111/nyas.12985
    1. Fregni F., Nitsche M., Loo C. K., Brunoni A., Marangolo P., Leite J., et al. . (2015). Regulatory considerations for the clinical and research use of Transcranial Direct Current Stimulation (tDCS): review and recommendations from an expert panel. Clin. Res. Regul. Aff. 32, 22–35. 10.3109/10601333.2015.980944
    1. Fritsch B., Reis J., Martinowich K., Schambra H. M., Ji Y., Cohen L. G., et al. . (2010). Direct current stimulation promotes BDNF-dependent synaptic plasticity: potential implications for motor learning. Neuron 66, 198–204. 10.1016/j.neuron.2010.03.035
    1. Fröhlich F., McCormick D. A. (2010). Endogenous electric fields may guide neocortical network activity. Neuron 67, 129–143. 10.1016/j.neuron.2010.06.005
    1. Galea J. M., Vazquez A., Pasricha N., de Xivry J.-J. O., Celnik P. (2011). Dissociating the roles of the cerebellum and motor cortex during adaptive learning: the motor cortex retains what the cerebellum learns. Cereb. Cortex 21, 1761–1770. 10.1093/cercor/bhq246
    1. Gladwin T. E., den Uyl T. E., Wiers R. W. (2012). Anodal tDCS of dorsolateral prefontal cortex during an implicit association test. Neurosci. Lett. 517, 82–86. 10.1016/j.neulet.2012.04.025
    1. Gomez Palacio Schjetnan A., Faraji J., Metz G. A., Tatsuno M., Luczak A. (2013). Transcranial direct current stimulation in stroke rehabilitation: a review of recent advancements. Stroke Res. Treat. 2013:170256. 10.1155/2013/170256
    1. Greer P. L., Greenberg M. E. (2008). From synapse to nucleus: calcium-dependent gene transcription in the control of synapse development and function. Neuron 59, 846–860. 10.1016/j.neuron.2008.09.002
    1. Herzfeld D. J., Pastor D., Haith A. M., Rossetti Y., Shadmehr R., O'Shea J. (2014). Contributions of the cerebellum and the motor cortex to acquisition and retention of motor memories. Neuroimage 98, 147–158. 10.1016/j.neuroimage.2014.04.076
    1. Ho K.-A., Taylor J. L., Chew T., Gálvez V., Alonzo A., Bai S., et al. . (2016). The Effect of Transcranial Direct Current Stimulation (tDCS) electrode size and current intensity on motor cortical excitability: evidence from single and repeated sessions. Brain Stimul. 9, 1–7. 10.1016/j.brs.2015.08.003
    1. Horvath J. C., Carter O., Forte J. D. (2014). Transcranial direct current stimulation: five important issues we aren't discussing (but probably should be). Front. Syst. Neurosci. 8:2. 10.3389/fnsys.2014.00002
    1. Horvath J. C., Forte J. D., 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. 10.1016/j.neuropsychologia.2014.11.021
    1. Islam N., Aftabuddin M., Moriwaki A., Hattori Y., Hori Y. (1995a). Increase in the calcium level following anodal polarization in the rat brain. Brain Res. 684, 206–208.
    1. Islam N., Moriwaki A., Hattori Y., Hayashi Y., Lu Y. F., Hori Y. (1995b). c-Fos expression mediated by N-methyl-D-aspartate receptors following anodal polarization in the rat brain. Exp. Neurol. 133, 25–31. 10.1006/exnr.1995.1004
    1. Jayaram G., Tang B., Pallegadda R., Vasudevan E. V. L., Celnik P., Bastian A. (2012). Modulating locomotor adaptation with cerebellar stimulation. J. Neurophysiol. 107, 2950–2957. 10.1152/jn.00645.2011
    1. Kabakov A. Y., Muller P. A., Pascual-Leone A., Jensen F. E., Rotenberg A. (2012). Contribution of axonal orientation to pathway-dependent modulation of excitatory transmission by direct current stimulation in isolated rat hippocampus. J. Neurophysiol. 107, 1881–1889. 10.1152/jn.00715.2011
    1. Kim S., Stephenson M. C., Morris P. G., Jackson S. 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. 10.1016/j.neuroimage.2014.05.070
    1. Kuo M.-F., Grosch J., Fregni F., Paulus W., Nitsche M. A. (2007). Focusing effect of acetylcholine on neuroplasticity in the human motor cortex. J. Neurosci. 27, 14442–14447. 10.1523/JNEUROSCI.4104-07.2007
    1. Kuo M.-F., Paulus W., Nitsche M. A. (2008). Boosting focally-induced brain plasticity by dopamine. Cereb. Cortex 18, 648–651. 10.1093/cercor/bhm098
    1. Lally N., Nord C. L., Walsh V., Roiser J. P. (2013). Does excitatory fronto-extracerebral tDCS lead to improved working memory performance? F1000Res 2:219. 10.12688/f1000research.2-219.v2
    1. Leffa D. T., de Souza A., Scarabelot V. L., Medeiros L. F., de Oliveira C., Grevet E. H., et al. . (2016). Transcranial direct current stimulation improves short-term memory in an animal model of attention-deficit/hyperactivity disorder. Eur. Neuropsychopharmacol. 26, 368–377. 10.1016/j.euroneuro.2015.11.012
    1. Li H., Lei X., Yan T., Li H., Huang B., Li L., et al. . (2015). The temporary and accumulated effects of transcranial direct current stimulation for the treatment of advanced Parkinson's disease monkeys. Sci. Rep. 5:12178. 10.1038/srep12178
    1. Liebetanz D., Nitsche M. A., Tergau F., Paulus W. (2002). Pharmacological approach to the mechanisms of transcranial DC-stimulation-induced after-effects of human motor cortex excitability. Brain 125, 2238–2247. 10.1093/brain/awf238
    1. McKay B. E., McRory J. E., Molineux M. L., Hamid J., Snutch T. P., Zamponi G. W., et al. . (2006). Ca(V)3 T-type calcium channel isoforms differentially distribute to somatic and dendritic compartments in rat central neurons. Eur. J. Neurosci. 24, 2581–2594. 10.1111/j.1460-9568.2006.05136.x
    1. Monai H., Ohkura M., Tanaka M., Oe Y., Konno A., Hirai H., et al. . (2016). Calcium imaging reveals glial involvement in transcranial direct current stimulation-induced plasticity in mouse brain. Nat. Commun. 7:11100. 10.1038/ncomms11100
    1. Moriwaki A., Islam N., Hattori Y., Hori Y. (1995). Induction of Fos expression following anodal polarization in rat brain. Psychiatry Clin. Neurosci. 49, 295–298.
    1. Morrissette D. A., Stahl S. M. (2014). Modulating the serotonin system in the treatment of major depressive disorder. CNS Spectr. 19(Suppl. 1), 57–67; quiz 54–57, 68. 10.1017/S1092852914000613
    1. Murphy D. N., Boggio P., Fregni F. (2009). Transcranial direct current stimulation as a therapeutic tool for the treatment of major depression: insights from past and recent clinical studies. Curr. Opin. Psychiatry 22, 306–311. 10.1097/YCO.0b013e32832a133f
    1. Nitsche M. A., Fricke K., Henschke U., Schlitterlau A., Liebetanz D., Lang N., et al. . (2003). Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans. J. Physiol. 553, 293–301. 10.1113/jphysiol.2003.049916
    1. Nitsche M. A., Grundey J., Liebetanz D., Lang N., Tergau F., Paulus W. (2004a). Catecholaminergic consolidation of motor cortical neuroplasticity in humans. Cereb. Cortex 14, 1240–1245. 10.1093/cercor/bhh085
    1. Nitsche M. A., Jaussi W., Liebetanz D., Lang N., Tergau F., Paulus W. (2004b). Consolidation of human motor cortical neuroplasticity by D-cycloserine. Neuropsychopharmacology 29, 1573–1578. 10.1038/sj.npp.1300517
    1. Nitsche M. A., Kuo M.-F., Karrasch R., Wächter B., Liebetanz D., Paulus W. (2009). Serotonin affects transcranial direct current-induced neuroplasticity in humans. Biol. Psychiatry 66, 503–508. 10.1016/j.biopsych.2009.03.022
    1. Nitsche M. A., Liebetanz D., Schlitterlau A., Henschke U., Fricke K., Frommann K., et al. . (2004c). GABAergic modulation of DC stimulation-induced motor cortex excitability shifts in humans. Eur. J. Neurosci. 19, 2720–2726. 10.1111/j.0953-816X.2004.03398.x
    1. Opitz A., Paulus W., Will S., Antunes A., Thielscher A. (2015). Determinants of the electric field during transcranial direct current stimulation. Neuroimage 109, 140–150. 10.1016/j.neuroimage.2015.01.033
    1. Pang P. T., Teng H. K., Zaitsev E., Woo N. T., Sakata K., Zhen S., et al. . (2004). Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal plasticity. Science 306, 487–491. 10.1126/science.1100135
    1. Peters H. T., Edwards D. J., Wortman-Jutt S., Page S. J. (2016). Moving forward by stimulating the brain: transcranial direct current stimulation in post-stroke hemiparesis. Front. Hum. Neurosci. 10:394. 10.3389/fnhum.2016.00394
    1. Polanía R., Nitsche M. A., Paulus W. (2011). Modulating functional connectivity patterns and topological functional organization of the human brain with transcranial direct current stimulation. Hum. Brain Mapp. 32, 1236–1249. 10.1002/hbm.21104
    1. Prehn K., Stengl H., Grittner U., Kosiolek R., Ölschläger A., Weidemann A., et al. . (2016). Effects of anodal transcranial direct current stimulation and serotonergic enhancement on memory performance in young and older adults. Neuropsychopharmacology.. [Epub ahead of print]. 10.1038/npp.2016.170
    1. Puri R., Hinder M. R., Fujiyama H., Gomez R., Carson R. G., Summers J. J. (2015). Duration-dependent effects of the BDNF Val66Met polymorphism on anodal tDCS induced motor cortex plasticity in older adults: a group and individual perspective. Front. Aging Neurosci. 7:107. 10.3389/fnagi.2015.00107
    1. Purpura D. P., Mcmurtry J. G. (1965). Intracellular activities and evoked potential changes during polarization of motor cortex. J. Neurophysiol. 28, 166–185.
    1. Radman T., Ramos R. L., Brumberg J. C., Bikson M. (2009). Role of cortical cell type and morphology in subthreshold and suprathreshold uniform electric field stimulation in vitro. Brain Stimul. 2, 215–228, 228.e1–3. 10.1016/j.brs.2009.03.007
    1. Rampersad S. M., Janssen A. M., Lucka F., Aydin Ü., Lanfer B., Lew S., et al. . (2014). Simulating transcranial direct current stimulation with a detailed anisotropic human head model. IEEE Trans. Neural Syst. Rehabil. Eng. 22, 441–452. 10.1109/TNSRE.2014.2308997
    1. Rappelsberger P., Pockberger H., Petsche H. (1982). The contribution of the cortical layers to the generation of the EEG: field potential and current source density analyses in the rabbit's visual cortex. Electroencephalogr. Clin. Neurophysiol. 53, 254–269.
    1. Reato D., Bikson M., Parra L. C. (2015). Lasting modulation of in vitro oscillatory activity with weak direct current stimulation. J. Neurophysiol. 113, 1334–1341. 10.1152/jn.00208.2014
    1. Reato D., Rahman A., Bikson M., Parra L. C. (2010). Low-intensity electrical stimulation affects network dynamics by modulating population rate and spike timing. J. Neurosci. 30, 15067–15079. 10.1523/JNEUROSCI.2059-10.2010
    1. Schambra H. M., Abe M., Luckenbaugh D. A., Reis J., Krakauer J. W., Cohen L. G. (2011). Probing for hemispheric specialization for motor skill learning: a transcranial direct current stimulation study. J. Neurophysiol. 106, 652–661. 10.1152/jn.00210.2011
    1. Stagg C. J., Best J. G., Stephenson M. C., O'Shea J., Wylezinska M., Kincses Z. T., et al. . (2009). Polarity-sensitive modulation of cortical neurotransmitters by transcranial stimulation. J. Neurosci. 29, 5202–5206. 10.1523/JNEUROSCI.4432-08.2009
    1. Stagg C. J., Nitsche M. A. (2011). Physiological basis of transcranial direct current stimulation. Neuroscientist 17, 37–53. 10.1177/1073858410386614
    1. Takano Y., Yokawa T., Masuda A., Niimi J., Tanaka S., Hironaka N. (2011). A rat model for measuring the effectiveness of transcranial direct current stimulation using fMRI. Neurosci. Lett. 491, 40–43. 10.1016/j.neulet.2011.01.004
    1. Takemura A., Kawano K. (2002). Sensory-to-motor processing of the ocular-following response. Neurosci. Res. 43, 201–206. 10.1016/S0168-0102(02)00044-5
    1. Tanaka J., Horiike Y., Matsuzaki M., Miyazaki T., Ellis-Davies G. C. R., Kasai H. (2008). Protein synthesis and neurotrophin-dependent structural plasticity of single dendritic spines. Science 319, 1683–1687. 10.1126/science.1152864
    1. Thirugnanasambandam N., Grundey J., Adam K., Drees A., Skwirba A. C., Lang N., et al. . (2011). Nicotinergic impact on focal and non-focal neuroplasticity induced by non-invasive brain stimulation in non-smoking humans. Neuropsychopharmacology 36, 879–886. 10.1038/npp.2010.227
    1. Thorpe S., Delorme A., Van Rullen R. (2001). Spike-based strategies for rapid processing. Neural Netw. 14, 715–725. 10.1016/S0893-6080(01)00083-1
    1. Villamar M. F., Wivatvongvana P., Patumanond J., Bikson M., Truong D. Q., Datta A., et al. . (2013). Focal modulation of the primary motor cortex in fibromyalgia using 4 × 1-ring high-definition transcranial direct current stimulation (HD-tDCS): immediate and delayed analgesic effects of cathodal and anodal stimulation. J. Pain 14, 371–383. 10.1016/j.jpain.2012.12.007
    1. Vines B. W., Nair D., Schlaug G. (2008). Modulating activity in the motor cortex affects performance for the two hands differently depending upon which hemisphere is stimulated. Eur. J. Neurosci. 28, 1667–1673. 10.1111/j.1460-9568.2008.06459.x
    1. Vollmann H., Conde V., Sewerin S., Taubert M., Sehm B., Witte O. W., et al. . (2013). Anodal transcranial direct current stimulation (tDCS) over supplementary motor area (SMA) but not pre-SMA promotes short-term visuomotor learning. Brain Stimul. 6, 101–107. 10.1016/j.brs.2012.03.018
    1. Wiethoff S., Hamada M., Rothwell J. C. (2014). Variability in response to transcranial direct current stimulation of the motor cortex. Brain Stimul. 7, 468–475. 10.1016/j.brs.2014.02.003
    1. Wilke S., List J., Mekle R., Lindenberg R., Bukowski M., Ott S., et al. . (2016). No effect of anodal transcranial direct current stimulation on gamma-aminobutyric acid levels in patients with recurrent mild traumatic brain injury. J. Neurotrauma. [Epub ahead of print]. 10.1089/neu.2016.4399
    1. Yoon K. J., Oh B.-M., Kim D.-Y. (2012). Functional improvement and neuroplastic effects of anodal transcranial direct current stimulation (tDCS) delivered 1 day vs. 1 week after cerebral ischemia in rats. Brain Res. 1452, 61–72. 10.1016/j.brainres.2012.02.062
    1. Zuchowski M. L., Timmann D., Gerwig M. (2014). Acquisition of conditioned eyeblink responses is modulated by cerebellar tDCS. Brain Stimul. 7, 525–531. 10.1016/j.brs.2014.03.010

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