Experimental Brain Research

, Volume 237, Issue 12, pp 3071–3088 | Cite as

Current challenges: the ups and downs of tACS

  • Nicholas S. BlandEmail author
  • Martin V. Sale


The non-invasive delivery of electric currents through the scalp (transcranial electrical stimulation) is a popular tool for neuromodulation, mostly due to its highly adaptable nature (waveform, montage) and tolerability at low intensities (< 2 mA). Applied rhythmically, transcranial alternating current stimulation (tACS) may entrain neural oscillations in a frequency- and phase-specific manner, providing a causal perspective on brain–behaviour relationships. While the past decade has seen many behavioural and electrophysiological effects of tACS that suggest entrainment-mediated effects in the brain, it has been difficult to reconcile such reports with the weak intracranial field strengths (< 1 V/m) achievable at conventional intensities. In this review, we first describe the ongoing challenges faced by users of tACS. We outline the biophysics of electrical brain stimulation and the factors that contribute to the weak field intensities achievable in the brain. Since the applied current predominantly shunts through the scalp—stimulating the nerves that innervate it—the plausibility of transcutaneous (rather than transcranial) effects of tACS is also discussed. In examining the effects of tACS on brain activity, the complex problem of salvaging electrophysiological recordings from artefacts of tACS is described. Nevertheless, these challenges by no means mark the rise and fall of tACS: the second part of this review outlines the recent advancements in the field. We describe some ways in which artefacts of tACS may be better managed using high-frequency protocols, and describe innovative methods for current interactions within the brain that offer either dynamic or more focal current distributions while also minimising transcutaneous effects.


Transcranial Stimulation Electric field Oscillation Artefact Phase 


Author contributions

Conceptualisation: NB and MS; formal analysis, investigation, and writing—original draft: NB; writing—review and editing: NB and MS.


NB and MS were funded by the Office of Naval Research (N62909-17-1-2139).

Compliance with ethical standards

Conflict of interest

The authors state that they have no conflict of interest.


  1. Abd Hamid AI, Gall C, Speck O, Antal A, Sabel BA (2015) Effects of alternating current stimulation on the healthy and diseased brain. Front Neurosci 9:391PubMedPubMedCentralGoogle Scholar
  2. Alagapan S, Schmidt SL, Lefebvre J, Hadar E, Shin HW, Frӧhlich F (2016) Modulation of cortical oscillations by low-frequency direct cortical stimulation is state- dependent. PLoS Biol 14(3):e1002424PubMedPubMedCentralGoogle Scholar
  3. Alekseichuk I, Falchier AY, Linn G, Xu T, Milham MP, Schroeder CE, Opitz A (2019a) Electric field dynamics in the brain during multi-electrode transcranial electric stimulation. Nat Commun 10(1):2573PubMedPubMedCentralGoogle Scholar
  4. Alekseichuk I, Mantell K, Shirinpour S, Opitz A (2019b) Comparative modeling of transcranial magnetic and electric stimulation in mouse, monkey, and human. NeuroImage 194:136–148PubMedGoogle Scholar
  5. Ali MM, Sellers KK, Fröhlich F (2013) Transcranial alternating current stimulation modulates large-scale cortical network activity by network resonance. J Neurosci 33(27):11262–11275PubMedPubMedCentralGoogle Scholar
  6. Anastassiou CA, Montgomery SM, Barahona M, Buzsáki G, Koch C (2010) The effect of spatially inhomogeneous extracellular electric fields on neurons. J Neurosci 30(5):1925–1936PubMedPubMedCentralGoogle Scholar
  7. Anastassiou CA, Perin R, Markram H, Koch C (2011) Ephaptic coupling of cortical neurons. Nat Neurosci 14(2):217–224PubMedGoogle Scholar
  8. Antal A, Herrmann CS (2016) Transcranial alternating current and random noise stimulation: possible mechanisms. Neural Plast. CrossRefPubMedPubMedCentralGoogle Scholar
  9. Antal A, Paulus W (2013) Transcranial alternating current stimulation (tACS). Front Hum Neurosci 7:317PubMedPubMedCentralGoogle Scholar
  10. Asamoah B, Khatoun A, McLaughlin M (2019a) tACS motor system effects can be caused by transcutaneous stimulation of peripheral nerves. Nat Commun 10(1):266PubMedPubMedCentralGoogle Scholar
  11. Asamoah B, Khatoun A, McLaughlin M (2019b) Analytical bias accounts for some of the reported effects of tACS on auditory perception. Brain Stimul 12(4):1001–1009PubMedGoogle Scholar
  12. Barker AT, Jalinous R, Freeston IL (1985) Non-invasive magnetic stimulation of human motor cortex. Lancet 325(8437):1106–1107Google Scholar
  13. Başar E, Schmiedt-Fehr C, Mathes B, Femir B, Emek-Savaş DD, Tülay E, Yener G (2016) What does the broken brain say to the neuroscientist? Oscillations and connectivity in schizophrenia, Alzheimer’s disease, and bipolar disorder. Int J Psychophysiol 103:135–148PubMedGoogle Scholar
  14. Bastos AM, Vezoli J, Fries P (2015) Communication through coherence with inter-areal delays. Curr Opin Neurobiol 31:173–180PubMedGoogle Scholar
  15. Batsikadze G, Moliadze V, Paulus W, Kuo MF, Nitsche MA (2013) Partially non-linear stimulation intensity-dependent effects of direct current stimulation on motor cortex excitability in humans. J Physiol 591(7):1987–2000PubMedPubMedCentralGoogle Scholar
  16. Berényi A, Belluscio M, Mao D, Buzsáki G (2012) Closed-loop control of epilepsy by transcranial electrical stimulation. Science 337(6095):735–737PubMedPubMedCentralGoogle Scholar
  17. Bergmann TO, Karabanov A, Hartwigsen G, Thielscher A, Siebner HR (2016) Combining non-invasive transcranial brain stimulation with neuroimaging and electrophysiology: Current approaches and future perspectives. NeuroImage 140:4–19PubMedGoogle Scholar
  18. Bestmann S, Walsh V (2017) Transcranial electrical stimulation. Curr Biol 27(23):R1258–R1262PubMedGoogle Scholar
  19. Bestmann S, de Berker AO, Bonaiuto J (2015) Understanding the behavioural consequences of noninvasive brain stimulation. TrendsCognit Sci 19(1):13–20Google Scholar
  20. Bikson M, Inoue M, Akiyama H, Deans JK, Fox JE, Miyakawa H, Jefferys JG (2004) Effects of uniform extracellular DC electric fields on excitability in rat hippocampal slices in vitro. J Physiol 557(1):175–190PubMedPubMedCentralGoogle Scholar
  21. Bikson M, Grossman P, Thomas C, Zannou AL, Jiang J, Adnan T, Brunoni AR (2016) Safety of transcranial direct current stimulation: evidence based update 2016. Brain Stimul 9(5):641–661PubMedPubMedCentralGoogle Scholar
  22. Bikson M, Brunoni AR, Charvet LE, Clark VP, Cohen LG, Deng ZD, Lim KO (2018) Rigor and reproducibility in research with transcranial electrical stimulation: an NIMH-sponsored workshop. Brain Stimul 11(3):465–480PubMedGoogle Scholar
  23. Bikson M, Esmaeilpour Z, Adair D, Kronberg G, Tyler WJ, Antal A, Edwards D (2019) Transcranial electrical stimulation nomenclature. Brain Stimul. CrossRefPubMedGoogle Scholar
  24. Bindman LJ, Lippold OCJ, Redfearn JWT (1962) Long-lasting changes in the level of the electrical activity of the cerebral cortex produced by polarizing currents. Nature 196(4854):584–585PubMedGoogle Scholar
  25. Bindman LJ, Lippold OCJ, Redfearn JWT (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(3):369–382PubMedPubMedCentralGoogle Scholar
  26. Bland NS, Mattingley JB, Sale MV (2018) No evidence for phase-specific effects of 40 Hz HD–tACS on multiple object tracking. Front Psychol 9:304PubMedPubMedCentralGoogle Scholar
  27. Brittain JS, Cagnan H, Mehta AR, Saifee TA, Edwards MJ, Brown P (2015) Distinguishing the central drive to tremor in Parkinson’s disease and essential tremor. J Neurosci 35(2):795–806PubMedPubMedCentralGoogle Scholar
  28. Brown CC (1975) Electroanesthesia and electrosleep. Am Psychol 30(3):402–410PubMedGoogle Scholar
  29. Cancelli A, Cottone C, Tecchio F, Truong DQ, Dmochowski J, Bikson M (2016) A simple method for EEG guided transcranial electrical stimulation without models. J Neural Eng 13(3):036022PubMedGoogle Scholar
  30. Carandini M, Ferster D (2000) Membrane potential and firing rate in cat primary visual cortex. J Neurosci 20(1):470–484PubMedPubMedCentralGoogle Scholar
  31. Chan CY, Nicholson C (1986) Modulation by applied electric fields of Purkinje and stellate cell activity in the isolated turtle cerebellum. J Physiol 371(1):89–114PubMedPubMedCentralGoogle Scholar
  32. Chan CY, Hounsgaard J, Nicholson C (1988) Effects of electric fields on transmembrane potential and excitability of turtle cerebellar Purkinje cells in vitro. J Physiol 402(1):751–771PubMedPubMedCentralGoogle Scholar
  33. Chander BS, Witkowski M, Braun C, Robinson SE, Born J, Cohen LG, Soekadar SR (2016) tACS phase locking of frontal midline theta oscillations disrupts working memory performance. Front Cell Neurosci 10:120PubMedPubMedCentralGoogle Scholar
  34. Chhatbar PY, Sawers JR, Feng W (2016) Response to the response to “does tDCS actually deliver DC stimulation?”. Brain Stimul Basic Transl Clin Res Neuromodul 9(6):952–954Google Scholar
  35. Chhatbar PY, Kautz SA, Takacs I, Rowland NC, Revuelta GJ, George MS, Feng W (2018) Evidence of transcranial direct current stimulation-generated electric fields at subthalamic level in human brain in vivo. Brain Stimul 11:727–733PubMedPubMedCentralGoogle Scholar
  36. Creutzfeldt OD, Fromm GH, Kapp H (1962) Influence of transcortical DC currents on cortical neuronal activity. Exp Neurol 5(6):436–452PubMedGoogle Scholar
  37. Datta A, Bansal V, Diaz J, Patel J, Reato D, Bikson M (2009) Gyri-precise head model of transcranial direct current stimulation: improved spatial focality using a ring electrode versus conventional rectangular pad. Brain Stimul 2(4):201–207PubMedPubMedCentralGoogle Scholar
  38. Datta A, Dmochowski JP, Guleyupoglu B, Bikson M, Fregni F (2013) Cranial electrotherapy stimulation and transcranial pulsed current stimulation: a computer based high-resolution modeling study. NeuroImage 65:280–287PubMedGoogle Scholar
  39. de Graaf TA, Thomson A, Janssens SE, van Bree S, ten Oever S, Sack AT (2019) Does alpha phase modulate visual target detection? Three experiments with tACS phase-based stimulus presentation. bioRxiv 675264.
  40. Deans JK, Powell AD, Jefferys JG (2007) Sensitivity of coherent oscillations in rat hippocampus to AC electric fields. J Physiol 583(2):555–565PubMedPubMedCentralGoogle Scholar
  41. DeSantana JM, Walsh DM, Vance C, Rakel BA, Sluka KA (2008) Effectiveness of transcutaneous electrical nerve stimulation for treatment of hyperalgesia and pain. Curr Rheumatol Rep 10(6):492–499PubMedPubMedCentralGoogle Scholar
  42. Dmochowski JP, Datta A, Bikson M, Su Y, Parra LC (2011) Optimized multi-electrode stimulation increases focality and intensity at target. J Neural Eng 8(4):046011PubMedGoogle Scholar
  43. Dowsett J, Herrmann CS (2016) Transcranial alternating current stimulation with sawtooth waves: simultaneous stimulation and EEG recording. Front Hum Neurosci 10:135PubMedPubMedCentralGoogle Scholar
  44. Edwards D, Cortes M, Datta A, Minhas P, Wassermann EM, Bikson M (2013) Physiological and modeling evidence for focal transcranial electrical brain stimulation in humans: a basis for high-definition tDCS. NeuroImage 74:266–275PubMedPubMedCentralGoogle Scholar
  45. Esmaeilpour Z, Schestatsky P, Bikson M, Brunoni AR, Pellegrinelli A, Piovesan FX, Fregni F (2017) Notes on human trials of transcranial direct current stimulation between 1960 and 1998. Front Hum Neurosci 11:71PubMedPubMedCentralGoogle Scholar
  46. Faria P, Hallett M, Miranda PC (2011) A finite element analysis of the effect of electrode area and inter-electrode distance on the spatial distribution of the current density in tDCS. J Neural Eng 8(6):066017PubMedPubMedCentralGoogle Scholar
  47. Fertonani A, Miniussi C (2017) Transcranial electrical stimulation: what we know and do not know about mechanisms. Neuroscientist 23(2):109–123PubMedGoogle Scholar
  48. Fertonani A, Ferrari C, Miniussi C (2015) What do you feel if I apply transcranial electric stimulation? Safety, sensations and secondary induced effects. Clin Neurophysiol 126(11):2181–2188PubMedGoogle Scholar
  49. Fiene M, Schwab BC, Misselhorn J, Herrmann CS, Schneider TR, Engel AK (2019) Phase-specific manipulation of neural oscillations by transcranial alternating current stimulation. bioRxiv 579631.
  50. Filmer HL, Dux PE, Mattingley JB (2014) Applications of transcranial direct current stimulation for understanding brain function. Trends Neurosci 37(12):742–753PubMedGoogle Scholar
  51. Francis JT, Gluckman BJ, Schiff SJ (2003) Sensitivity of neurons to weak electric fields. J Neurosci 23(19):7255–7261PubMedPubMedCentralGoogle Scholar
  52. Fries P (2015) Rhythms for cognition: communication through coherence. Neuron 88(1):220–235PubMedPubMedCentralGoogle Scholar
  53. Fröhlich F, McCormick DA (2010) Endogenous electric fields may guide neocortical network activity. Neuron 67(1):129–143PubMedPubMedCentralGoogle Scholar
  54. Gartside IB (1968a) Mechanisms of sustained increases of firing rate of neurones in the rat cerebral cortex after polarization: reverberating circuits or modification of synaptic conductance? Nature 220(5165):382–383PubMedGoogle Scholar
  55. Gartside IB (1968b) Mechanisms of sustained increases of firing rate of neurones in the rat cerebral cortex after polarization: role of protein synthesis. Nature 220(5165):383–384PubMedGoogle Scholar
  56. Geisler CD, Goldberg JM (1966) A stochastic model of the repetitive activity of neurons. Biophys J 6(1):53–69PubMedPubMedCentralGoogle Scholar
  57. Goldsworthy MR, Hordacre B (2017) Dose dependency of transcranial direct current stimulation: implications for neuroplasticity induction in health and disease. J Physiol 595(11):3265–3266PubMedPubMedCentralGoogle Scholar
  58. Grossman N, Bono D, Dedic N, Kodandaramaiah SB, Rudenko A, Suk HJ, Pascual-Leone A (2017) Noninvasive deep brain stimulation via temporally interfering electric fields. Cell 169(6):1029–1041PubMedPubMedCentralGoogle Scholar
  59. Gundlach C, Müller MM, Nierhaus T, Villringer A, Sehm B (2016) Phasic modulation of human somatosensory perception by transcranially applied oscillating currents. Brain Stimul 9(5):712–719PubMedGoogle Scholar
  60. Hahn C, Rice J, Macuff S, Minhas P, Rahman A, Bikson M (2013) Methods for extra-low voltage transcranial direct current stimulation: current and time dependent impedance decreases. Clin Neurophysiol 124(3):551–556PubMedGoogle Scholar
  61. Hanslmayr S, Matuschek J, Fellner MC (2014) Entrainment of prefrontal beta oscillations induces an endogenous echo and impairs memory formation. Curr Biol 24(8):904–909PubMedGoogle Scholar
  62. Helfrich RF, Knepper H, Nolte G, Strüber D, Rach S, Herrmann CS, Engel AK (2014a) Selective modulation of interhemispheric functional connectivity by HD–tACS shapes perception. PLoS Biol 12(12):e1002031PubMedPubMedCentralGoogle Scholar
  63. Helfrich RF, Schneider TR, Rach S, Trautmann-Lengsfeld SA, Engel AK, Herrmann CS (2014b) Entrainment of brain oscillations by transcranial alternating current stimulation. Curr Biol 24(3):333–339PubMedPubMedCentralGoogle Scholar
  64. Helfrich RF, Herrmann CS, Engel AK, Schneider TR (2016) Different coupling modes mediate cortical cross-frequency interactions. NeuroImage 140:76–82PubMedGoogle Scholar
  65. Héroux ME, Loo CK, Taylor JL, Gandevia SC (2017) Questionable science and reproducibility in electrical brain stimulation research. PLoS One 12(4):e0175635PubMedPubMedCentralGoogle Scholar
  66. Herring JD, Esterer S, Marshall TR, Jensen O, Bergmann TO (2019) Low-frequency alternating current stimulation rhythmically suppresses gamma-band oscillations and impairs perceptual performance. NeuroImage 184:440–449PubMedGoogle Scholar
  67. Herrmann CS, Strüber D (2017) What can transcranial alternating current stimulation tell us about brain oscillations? Curr Behav Neurosci Rep 4(2):128–137Google Scholar
  68. Herrmann CS, Strüber D, Helfrich RF, Engel AK (2016) EEG oscillations: from correlation to causality. Int J Psychophysiol 103:12–21PubMedPubMedCentralGoogle Scholar
  69. Horvath JC, Forte JD, Carter O (2015a) 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 66:213–236PubMedPubMedCentralGoogle Scholar
  70. Horvath JC, Forte JD, Carter O (2015b) Quantitative review finds no evidence of cognitive effects in healthy populations from single-session transcranial direct current stimulation (tDCS). Brain Stimul 8(3):535–550PubMedPubMedCentralGoogle Scholar
  71. Huang Y, Parra LC (2019) Can transcranial electric stimulation with multiple electrodes reach deep targets? Brain Stimul 12(1):30–40PubMedGoogle Scholar
  72. Huang Y, Liu AA, Lafon B, Friedman D, Dayan M, Wang X, Parra LC (2017) Measurements and models of electric fields in the in vivo human brain during transcranial electric stimulation. eLife 6:e18834PubMedPubMedCentralGoogle Scholar
  73. Jackson MP, Rahman A, Lafon B, Kronberg G, Ling D, Parra LC, Bikson M (2016) Animal models of transcranial direct current stimulation: methods and mechanisms. Clin Neurophysiol 127(11):3425–3454PubMedPubMedCentralGoogle Scholar
  74. Jacobson GA, Diba K, Yaron-Jakoubovitch A, Oz Y, Koch C, Segev I, Yarom Y (2005) Subthreshold voltage noise of rat neocortical pyramidal neurones. J Physiol 564(1):145–160PubMedPubMedCentralGoogle Scholar
  75. Jefferys JGR, Deans J, Bikson M, Fox J (2003) Effects of weak electric fields on the activity of neurons and neuronal networks. Radiat Prot Dosimetry 106(4):321–323PubMedGoogle Scholar
  76. Kanai R, Chaieb L, Antal A, Walsh V, Paulus W (2008) Frequency-dependent electrical stimulation of the visual cortex. Curr Biol 18(23):1839–1843PubMedGoogle Scholar
  77. Kar K, Krekelberg B (2012) Transcranial electrical stimulation over visual cortex evokes phosphenes with a retinal origin. J Neurophysiol 108(8):2173–2178PubMedPubMedCentralGoogle Scholar
  78. Karabanov AN, Saturnino GB, Thielscher A, Siebner HR (2019) Can transcranial electrical stimulation localize brain function? Front Psychol 10:213PubMedPubMedCentralGoogle Scholar
  79. Kasten FH, Herrmann CS (2019) Recovering brain dynamics during concurrent tACS-M/EEG: an overview of analysis approaches and their methodological and interpretational pitfalls. Brain Topogr. CrossRefPubMedPubMedCentralGoogle Scholar
  80. Kasten FH, Negahbani E, Fröhlich F, Herrmann CS (2018) Non-linear transfer characteristics of stimulation and recording hardware account for spurious low-frequency artifacts during amplitude modulated transcranial alternating current stimulation (AM-tACS). NeuroImage 179:134–143PubMedGoogle Scholar
  81. Kavirajan HC, Lueck K, Chuang K (2014) Alternating current cranial electrotherapy stimulation (CES) for depression. Cochrane Database Syst Rev 7:Article CD010521Google Scholar
  82. Khatoun A, Breukers J, de Beeck SO, Nica IG, Aerts JM, Seynaeve L, Mc Laughlin M (2018) Using high-amplitude and focused transcranial alternating current stimulation to entrain physiological tremor. Sci Rep 8(1):4927PubMedPubMedCentralGoogle Scholar
  83. Kim JH, Kim DW, Chang WH, Kim YH, Kim K, Im CH (2014) Inconsistent outcomes of transcranial direct current stimulation may originate from anatomical differences among individuals: electric field simulation using individual MRI data. Neurosci Lett 564:6–10PubMedGoogle Scholar
  84. Krause MR, Zanos TP, Csorba BA, Pilly PK, Choe J, Phillips ME, Pack CC (2017) Transcranial direct current stimulation facilitates associative learning and alters functional connectivity in the primate brain. Curr Biol 27(20):3086–3096PubMedGoogle Scholar
  85. Krause MR, Vieira PG, Csorba BA, Pilly PK, Pack CC (2019) Transcranial alternating current stimulation entrains single-neuron activity in the primate brain. Proc Natl Acad Sci 116(12):5747–5755PubMedGoogle Scholar
  86. Kwan A, Forbes PA, Mitchell DE, Blouin JS, Cullen KE (2019) Neural substrates, dynamics and thresholds of galvanic vestibular stimulation in the behaving primate. Nat Commun 10(1):1904PubMedPubMedCentralGoogle Scholar
  87. Laakso I, Hirata A (2013) Computational analysis shows why transcranial alternating current stimulation induces retinal phosphenes. J Neural Eng 10(4):046009PubMedGoogle Scholar
  88. Lafon B, Henin S, Huang Y, Friedman D, Melloni L, Thesen T, Liu A (2017) Low frequency transcranial electrical stimulation does not entrain sleep rhythms measured by human intracranial recordings. Nat Commun 8(1):1199PubMedPubMedCentralGoogle Scholar
  89. Lefaucheur JP, André-Obadia N, Antal A, Ayache SS, Baeken C, Benninger DH, Devanne H (2014) Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol 125(11):2150–2206PubMedGoogle Scholar
  90. Liu A, Vöröslakos M, Kronberg G, Henin S, Krause MR, Huang Y, Berényi A (2018) Immediate neurophysiological effects of transcranial electrical stimulation. Nat Commun 9(1):5092PubMedPubMedCentralGoogle Scholar
  91. Mäkelä N, Sarvas J, Ilmoniemi RJ (2017) A simple reason why beamformer may (not) remove the tACS-induced artifact in MEG. Brain Stimul 10(4):e66–e67Google Scholar
  92. Marino M, Liu Q, Del Castello M, Corsi C, Wenderoth N, Mantini D (2018a) Heart–Brain interactions in the MR environment: characterization of the ballistocardiogram in EEG signals collected during simultaneous fMRI. Brain Topogr 31(3):337–345PubMedGoogle Scholar
  93. Marino M, Liu Q, Koudelka V, Porcaro C, Hlinka J, Wenderoth N, Mantini D (2018b) Adaptive optimal basis set for BCG artifact removal in simultaneous EEG-fMRI. Sci Rep 8(1):8902PubMedPubMedCentralGoogle Scholar
  94. Marshall L, Helgadóttir H, Mölle M, Born J (2006) Boosting slow oscillations during sleep potentiates memory. Nature 444(7119):610–613PubMedGoogle Scholar
  95. Marshall TR, Esterer S, Herring JD, Bergmann TO, Jensen O (2016) On the relationship between cortical excitability and visual oscillatory responses—a concurrent tDCS–MEG study. NeuroImage 140:41–49PubMedGoogle Scholar
  96. Matsumoto H, Ugawa Y (2017) Adverse events of tDCS and tACS: a review. Clin Neurophysiol Pract 2:19–25PubMedGoogle Scholar
  97. Mehta AR, Brittain JS, Brown P (2014) The selective influence of rhythmic cortical versus cerebellar transcranial stimulation on human physiological tremor. J Neurosci 34(22):7501–7508PubMedPubMedCentralGoogle Scholar
  98. 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(2):260–268PubMedPubMedCentralGoogle Scholar
  99. Merton PA, Morton HB (1980) Stimulation of the cerebral cortex in the intact human subject. Nature 285(5762):227PubMedGoogle Scholar
  100. Minami S, Amano K (2017) Illusory jitter perceived at the frequency of alpha oscillations. Curr Biol 27(15):2344–2351PubMedPubMedCentralGoogle Scholar
  101. Miranda PC, Lomarev M, Hallett M (2006) Modeling the current distribution during transcranial direct current stimulation. Clin Neurophysiol 117(7):1623–1629PubMedGoogle Scholar
  102. Miranda PC, Mekonnen A, Salvador R, Ruffini G (2013) The electric field in the cortex during transcranial current stimulation. NeuroImage 70:48–58PubMedGoogle Scholar
  103. Miyaguchi S, Otsuru N, Kojima S, Yokota H, Saito K, Inukai Y, Onishi H (2019) Gamma tACS over M1 and cerebellar hemisphere improves motor performance in a phase-specific manner. Neurosci Lett 694:64–68PubMedGoogle Scholar
  104. Modolo J, Denoyer Y, Wendling F, Benquet P (2018) Physiological effects of low-magnitude electric fields on brain activity: advances from in vitro, in vivo and in silico models. Curr Opin Biomed Eng 8:38–44PubMedGoogle Scholar
  105. Monai H, Hirase H (2018) Astrocytes as a target of transcranial direct current stimulation (tDCS) to treat depression. Neurosci Res 126:15–21PubMedGoogle Scholar
  106. Negahbani E, Kasten FH, Herrmann CS, Fröhlich F (2018) Targeting alpha-band oscillations in a cortical model with amplitude-modulated high-frequency transcranial electric stimulation. NeuroImage 173:3–12PubMedPubMedCentralGoogle Scholar
  107. Neuling T, Rach S, Wagner S, Wolters CH, Herrmann CS (2012) Good vibrations: oscillatory phase shapes perception. NeuroImage 63(2):771–778PubMedGoogle Scholar
  108. Neuling T, Ruhnau P, Weisz N, Herrmann CS, Demarchi G (2017) Faith and oscillations recovered: on analyzing EEG/MEG signals during tACS. NeuroImage 147:960–963PubMedGoogle Scholar
  109. Nimmrich V, Draguhn A, Axmacher N (2015) Neuronal network oscillations in neurodegenerative diseases. NeuroMol Med 17(3):270–284Google Scholar
  110. Nitsche MA, Paulus W (2000) Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol 527(3):633–639PubMedPubMedCentralGoogle Scholar
  111. Nitsche MA, Paulus W (2001) Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans. Neurology 57(10):1899–1901PubMedPubMedCentralGoogle Scholar
  112. Nitsche MA, Nitsche MS, Klein CC, Tergau F, Rothwell JC, Paulus W (2003) Level of action of cathodal DC polarisation induced inhibition of the human motor cortex. Clin Neurophysiol 114(4):600–604PubMedPubMedCentralGoogle Scholar
  113. Nitsche MA, Cohen LG, Wassermann EM, Priori A, Lang N, Antal A, Pascual- Leone A (2008) Transcranial direct current stimulation: state of the art 2008. Brain Stimul 1(3):206–223PubMedGoogle Scholar
  114. Noury N, Siegel M (2017) Phase properties of transcranial electrical stimulation artifacts in electrophysiological recordings. NeuroImage 158:406–416PubMedGoogle Scholar
  115. Noury N, Siegel M (2018) Analyzing EEG and MEG signals recorded during tES, a reply. NeuroImage 167:53–61PubMedGoogle Scholar
  116. Noury N, Hipp JF, Siegel M (2016) Physiological processes non-linearly affect electrophysiological recordings during transcranial electric stimulation. NeuroImage 140:99–109PubMedGoogle Scholar
  117. Opitz A, Paulus W, Will S, Antunes A, Thielscher A (2015) Determinants of the electric field during transcranial direct current stimulation. NeuroImage 109:140–150PubMedGoogle Scholar
  118. Opitz A, Falchier A, Yan CG, Yeagle EM, Linn GS, Megevand P, Schroeder CE (2016) Spatiotemporal structure of intracranial electric fields induced by transcranial electric stimulation in humans and nonhuman primates. Sci Rep 6:31236PubMedPubMedCentralGoogle Scholar
  119. Opitz A, Falchier A, Linn GS, Milham MP, Schroeder CE (2017) Limitations of ex vivo measurements for in vivo neuroscience. Proc Natl Acad Sci 114(20):5243–5246PubMedGoogle Scholar
  120. Ozen S, Sirota A, Belluscio MA, Anastassiou CA, Stark E, Koch C, Buzsáki G (2010) Transcranial electric stimulation entrains cortical neuronal populations in rats. J Neurosci 30(34):11476–11485PubMedPubMedCentralGoogle Scholar
  121. Payne NA, Prudic J (2009) Electroconvulsive therapy Part I: a perspective on the evolution and current practice of ECT. J Psychiatr Pract 15(5):346–368PubMedPubMedCentralGoogle Scholar
  122. Plewnia C, Rilk AJ, Soekadar SR, Arfeller C, Huber HS, Sauseng P, Gerloff C (2008) Enhancement of long-range EEG coherence by synchronous bifocal transcranial magnetic stimulation. Eur J Neurosci 27(6):1577–1583PubMedGoogle Scholar
  123. Polanía R, Nitsche MA, Korman C, Batsikadze G, Paulus W (2012) The importance of timing in segregated theta phase-coupling for cognitive performance. Curr Biol 22(14):1314–1318PubMedGoogle Scholar
  124. Polanía R, Moisa M, Opitz A, Grueschow M, Ruff CC (2015) The precision of value- based choices depends causally on fronto-parietal phase coupling. Nat Commun 6:8090PubMedPubMedCentralGoogle Scholar
  125. Polanía R, Nitsche MA, Ruff CC (2018) Studying and modifying brain function with non-invasive brain stimulation. Nat Neurosci 21:174–187PubMedGoogle Scholar
  126. 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(4–6):208–214PubMedPubMedCentralGoogle Scholar
  127. Priori A (2003) Brain polarization in humans: a reappraisal of an old tool for prolonged non-invasive modulation of brain excitability. Clin Neurophysiol 114(4):589–595PubMedGoogle Scholar
  128. Purpura DP, McMurtry JG (1965) Intracellular activities and evoked potential changes during polarization of motor cortex. J Neurophysiol 28(1):166–185PubMedGoogle Scholar
  129. Radman T, Su Y, An JH, Parra LC, Bikson M (2007) Spike timing amplifies the effect of electric fields on neurons: implications for endogenous field effects. J Neurosci 27(11):3030–3036PubMedPubMedCentralGoogle Scholar
  130. Radman T, Ramos RL, Brumberg JC, Bikson M (2009) Role of cortical cell type and morphology in subthreshold and suprathreshold uniform electric field stimulation in vitro. Brain Stimul 2(4):215–228PubMedPubMedCentralGoogle Scholar
  131. Rahman A, Reato D, Arlotti M, Gasca F, Datta A, Parra LC, Bikson M (2013) Cellular effects of acute direct current stimulation: somatic and synaptic terminal effects. J Physiol 591(10):2563–2578PubMedPubMedCentralGoogle Scholar
  132. Rawji V, Ciocca M, Zacharia A, Soares D, Truong D, Bikson M, Bestmann S (2018) tDCS changes in motor excitability are specific to orientation of current flow. Brain Stimul 11(2):289–298PubMedPubMedCentralGoogle Scholar
  133. Reato D, Rahman A, Bikson M, Parra LC (2010) Low-intensity electrical stimulation affects network dynamics by modulating population rate and spike timing. J Neurosci 30(45):15067–15079PubMedPubMedCentralGoogle Scholar
  134. Reato D, Rahman A, Bikson M, Parra LC (2013) Effects of weak transcranial alternating current stimulation on brain activity—a review of known mechanisms from animal studies. Front Hum Neurosci 7:687PubMedPubMedCentralGoogle Scholar
  135. Reinhart RM, Nguyen JA (2019) Working memory revived in older adults by synchronizing rhythmic brain circuits. Nat Neurosci 22(5):820–827PubMedPubMedCentralGoogle Scholar
  136. Riecke L, Formisano E, Herrmann CS, Sack AT (2015a) 4-Hz transcranial alternating current stimulation phase modulates hearing. Brain Stimul 8(4):777–783PubMedGoogle Scholar
  137. Riecke L, Sack AT, Schroeder CE (2015b) Endogenous delta/theta sound-brain phase entrainment accelerates the buildup of auditory streaming. Curr Biol 25(24):3196–3201PubMedGoogle Scholar
  138. Ruffini G, Wendling F, Merlet I, Molaee-Ardekani B, Mekonnen A, Salvador R, Miranda PC (2013) Transcranial current brain stimulation (tCS): models and technologies. IEEE Trans Neural Syst Rehabil Eng 21(3):333–345PubMedGoogle Scholar
  139. Ruhnau P, Neuling T, Fuscá M, Herrmann CS, Demarchi G, Weisz N (2016) Eyes wide shut: transcranial alternating current stimulation drives alpha rhythm in a state dependent manner. Sci Rep 6:27138PubMedPubMedCentralGoogle Scholar
  140. Ruhnau P, Rufener KS, Heinze HJ, Zaehle T (2018) Sailing in a sea of disbelief: in vivo measurements of transcranial electric stimulation in human subcortical structures. Brain Stimul 11(1):241–243PubMedGoogle Scholar
  141. Ruohonen J, Karhu J (2012) tDCS possibly stimulates glial cells. Clin Neurophysiol 123(10):2006–2009PubMedGoogle Scholar
  142. Sadleir RJ, Vannorsdall TD, Schretlen DJ, Gordon B (2010) Transcranial direct current stimulation (tDCS) in a realistic head model. NeuroImage 51(4):1310–1318PubMedGoogle Scholar
  143. Saturnino GB, Madsen KH, Siebner HR, Thielscher A (2017) How to target inter-regional phase synchronization with dual-site transcranial alternating current stimulation. NeuroImage 163:68–80PubMedGoogle Scholar
  144. Schutter DJ (2016) Cutaneous retinal activation and neural entrainment in transcranial alternating current stimulation: a systematic review. NeuroImage 140:83–88PubMedGoogle Scholar
  145. Schutter DJ, Hortensius R (2010) Retinal origin of phosphenes to transcranial alternating current stimulation. Clin Neurophysiol 121(7):1080–1084PubMedGoogle Scholar
  146. Schutter DJ, Wischnewski M (2016) A meta-analytic study of exogenous oscillatory electric potentials in neuroenhancement. Neuropsychologia 86:110–118PubMedGoogle Scholar
  147. Schwiedrzik CM (2009) Retina or visual cortex? The site of phosphene induction by transcranial alternating current stimulation. Front Integr Neurosci 3:6PubMedPubMedCentralGoogle Scholar
  148. Shekelle PG, Cook IA, Miake-Lye IM, Booth MS, Beroes JM, Mak S (2018) Benefits and harms of cranial electrical stimulation for chronic painful conditions, depression, anxiety, and insomnia: a systematic review. Ann Intern Med 168(6):414–421PubMedGoogle Scholar
  149. Soekadar SR, Herring JD, McGonigle D (2016) Transcranial electric stimulation (tES) and neuroimaging: the state-of-the-art, new insights and prospects in basic and clinical neuroscience. NeuroImage 140:1–3PubMedGoogle Scholar
  150. Spaak E, de Lange FP, Jensen O (2014) Local entrainment of alpha oscillations by visual stimuli causes cyclic modulation of perception. J Neurosci 34(10):3536–3544PubMedPubMedCentralGoogle Scholar
  151. Tan J, Iyer KK, Tang AD, Jamil A, Martins RN, Sohrabi HR, Fujiyama H (2018) Modulating functional connectivity with non-invasive brain stimulation for the investigation and alleviation of age-associated declines in response inhibition: a narrative review. NeuroImage 185:490–512PubMedGoogle Scholar
  152. Terzuolo CA, Bullock TH (1956) Measurement of imposed voltage gradient adequate to modulate neuronal firing. Proc Natl Acad Sci USA 42(9):687–694PubMedGoogle Scholar
  153. Thut G, Bergmann TO, Fröhlich F, Soekadar SR, Brittain JS, Valero-Cabré A, Herrmann CS (2017) Guiding transcranial brain stimulation by EEG/MEG to interact with ongoing brain activity and associated functions: a position paper. Clin Neurophysiol 128(5):843–857PubMedPubMedCentralGoogle Scholar
  154. Tseng P, Chang YT, Chang CF, Liang WK, Juan CH (2016) The critical role of phase difference in gamma oscillation within the temporoparietal network for binding visual working memory. Sci Rep 6:32138PubMedPubMedCentralGoogle Scholar
  155. Veniero D, Vossen A, Gross J, Thut G (2015) Lasting EEG/MEG aftereffects of rhythmic transcranial brain stimulation: level of control over oscillatory network activity. Front Cell Neurosci 9:477PubMedPubMedCentralGoogle Scholar
  156. Veniero D, Strüber D, Thut G, Herrmann CS (2019) Noninvasive brain stimulation techniques can modulate cognitive processing. Organ Res Methods 22(1):116–147Google Scholar
  157. Vöröslakos M, Takeuchi Y, Brinyiczki K, Zombori T, Oliva A, Fernández-Ruiz A, Berényi A (2018) Direct effects of transcranial electric stimulation on brain circuits in rats and humans. Nat Commun 9(1):483PubMedPubMedCentralGoogle Scholar
  158. Vossen A, Gross J, Thut G (2015) Alpha power increase after transcranial alternating current stimulation at alpha frequency (α-tACS) reflects plastic changes rather than entrainment. Brain Stimul 8(3):499–508PubMedPubMedCentralGoogle Scholar
  159. Vosskuhl J, Strüber D, Herrmann CS (2018) Non-invasive brain stimulation: a paradigm shift in understanding brain oscillations. Front Hum Neurosci 12:211PubMedPubMedCentralGoogle Scholar
  160. Wagner S, Rampersad SM, Aydin Ü, Vorwerk J, Oostendorp TF, Neuling T, Wolters CH (2013) Investigation of tDCS volume conduction effects in a highly realistic head model. J Neural Eng 11(1):016002PubMedGoogle Scholar
  161. Widge AS (2018) Cross-species neuromodulation from high-intensity transcranial electrical stimulation. Trends Cognit Sci 22(5):372–374Google Scholar
  162. Wischnewski M, Schutter DJ (2017) After-effects of transcranial alternating current stimulation on evoked delta and theta power. Clin Neurophysiol 128(11):2227–2232PubMedGoogle Scholar
  163. Witkowski M, Garcia-Cossio E, Chander BS, Braun C, Birbaumer N, Robinson SE, Soekadar SR (2016) Mapping entrained brain oscillations during transcranial alternating current stimulation (tACS). NeuroImage 140:89–98PubMedGoogle Scholar
  164. Yavari F, Jamil A, Samani MM, Vidor LP, Nitsche MA (2018) Basic and functional effects of transcranial electrical stimulation (tES)—an introduction. Neurosci Biobehav Rev 85:81–92PubMedGoogle Scholar
  165. Zaehle T, Rach S, Herrmann CS (2010) Transcranial alternating current stimulation enhances individual alpha activity in human EEG. PLoS One 5(11):e13766PubMedPubMedCentralGoogle Scholar
  166. Zoefel B, Davis MH, Valente G, Riecke L (2019) How to test for phasic modulation of neural and behavioural responses. NeuroImage 202:116175. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Queensland Brain InstituteThe University of QueenslandSt LuciaAustralia
  2. 2.School of Health and Rehabilitation SciencesThe University of QueenslandSt LuciaAustralia

Personalised recommendations