Clinical research with transcranial direct current stimulation (tDCS): challenges and future directions

Andre Russowsky Brunoni, Michael A Nitsche, Nadia Bolognini, Marom Bikson, Tim Wagner, Lotfi Merabet, Dylan J Edwards, Antoni Valero-Cabre, Alexander Rotenberg, Alvaro Pascual-Leone, Roberta Ferrucci, Alberto Priori, Paulo Sergio Boggio, Felipe Fregni, Andre Russowsky Brunoni, Michael A Nitsche, Nadia Bolognini, Marom Bikson, Tim Wagner, Lotfi Merabet, Dylan J Edwards, Antoni Valero-Cabre, Alexander Rotenberg, Alvaro Pascual-Leone, Roberta Ferrucci, Alberto Priori, Paulo Sergio Boggio, Felipe Fregni

Abstract

Background: Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low-intensity, direct current to cortical areas facilitating or inhibiting spontaneous neuronal activity. In the past 10 years, tDCS physiologic mechanisms of action have been intensively investigated giving support for the investigation of its applications in clinical neuropsychiatry and rehabilitation. However, new methodologic, ethical, and regulatory issues emerge when translating the findings of preclinical and phase I studies into phase II and III clinical studies. The aim of this comprehensive review is to discuss the key challenges of this process and possible methods to address them.

Methods: We convened a workgroup of researchers in the field to review, discuss, and provide updates and key challenges of tDCS use in clinical research.

Main findings/discussion: We reviewed several basic and clinical studies in the field and identified potential limitations, taking into account the particularities of the technique. We review and discuss the findings into four topics: (1) mechanisms of action of tDCS, parameters of use and computer-based human brain modeling investigating electric current fields and magnitude induced by tDCS; (2) methodologic aspects related to the clinical research of tDCS as divided according to study phase (ie, preclinical, phase I, phase II, and phase III studies); (3) ethical and regulatory concerns; and (4) future directions regarding novel approaches, novel devices, and future studies involving tDCS. Finally, we propose some alternative methods to facilitate clinical research on tDCS.

Conflict of interest statement

Conflict of Interest: AP and RF have some stock options in the neurostimulation company Newronika srl (Milan, Italy).

Copyright © 2012 Elsevier Inc. All rights reserved.

References

    1. Fregni F, Boggio PS, Nitsche MA, Marcolin MA, Rigonatti SP, Pascual-Leone A. Treatment of major depression with transcranial direct current stimulation. Bipolar disorders. 2006 Apr;8(2):203–204.
    1. Boggio PS, Rigonatti SP, Ribeiro RB, Myczkowski ML, Nitsche MA, Pascual-Leone A, et al. A randomized, double-blind clinical trial on the efficacy of cortical direct current stimulation for the treatment of major depression. Int J Neuropsychopharmacol. 2008 Mar;11(2):249–254.
    1. Fregni F, Boggio PS, Nitsche M, Bermpohl F, Antal A, Feredoes E, et al. Anodal transcranial direct current stimulation of prefrontal cortex enhances working memory. Exp Brain Res. 2005 Sep;166(1):23–30.
    1. Rigonatti SP, Boggio PS, Myczkowski ML, Otta E, Fiquer JT, Ribeiro RB, et al. Transcranial direct stimulation and fluoxetine for the treatment of depression. Eur Psychiatry. 2008 Jan;23(1):74–76.
    1. Ferrucci R, Bortolomasi M, Vergari M, Tadini L, Salvoro B, Giacopuzzi M, et al. Transcranial direct current stimulation in severe, drug-resistant major depression. J Affect Disord. 2009 Nov;118(1–3):215–219.
    1. Elmer S, Burkard M, Renz B, Meyer M, Jancke L. Direct current induced short-term modulation of the left dorsolateral prefrontal cortex while learning auditory presented nouns. Behav Brain Funct. 2009 Jul 15;5(1):29.
    1. Ferrucci R, Bortolomasi M, Brunoni AR, Vergares M, Tadini L, Giacopuzzi M, et al. Comparative benefits of Transcranial Direct Current Stimulation (tDCS) treatment in patients with mild/moderate vs. severe depression. Clinical Neuropsychiatry. 2009;6:246–251.
    1. Ferrucci R, Marceglia S, Vergari M, Cogiamanian F, Mrakic-Sposta S, Mameli F, et al. Cerebellar transcranial direct current stimulation impairs the practice-dependent proficiency increase in working memory. J Cogn Neurosci. 2008 Sep;20(9):1687–1697.
    1. Largus S. De compositionibus medicamentorum. Paris 1529.
    1. Marshall L, Molle M, Siebner HR, Born J. Bifrontal transcranial direct current stimulation slows reaction time in a working memory task. BMC Neurosci. 2005 Apr 8;6(1):23.
    1. Kellaway P. The part played by the electric fish in the early history of bioelectricity and electrotherapy. Bull Hist Med. 1946;20:112–137.
    1. Brunoni AR, Ferrucci R, Bortolomasi M, Vergari M, Tadini L, Boggio PS, et al. Transcranial direct current stimulation (tDCS) in unipolar vs. bipolar depressive disorder. Progress in neuro-psychopharmacology & biological psychiatry. 2011 Sep 17;35(1):96–101.
    1. Boggio PS, Fregni F, Valasek C, Ellwood S, Chi R, Gallate J, et al. Temporal lobe cortical electrical stimulation during the encoding and retrieval phase reduces false memories. PLoS One. 2009;4(3):e4959.
    1. Zago S, Ferrucci R, Fregni F, Priori A. Bartholow, Sciamanna, Alberti: Pioneers in the Electrical Stimulation of the Exposed Human Cerebral Cortex. Neuroscientist. 2008 Jan 24;14(5):521–528.
    1. Marshall L, Molle M, Hallschmid M, Born J. Transcranial direct current stimulation during sleep improves declarative memory. J Neurosci. 2004 Nov 3;24(44):9985–9992.
    1. Fecteau S, Knoch D, Fregni F, Sultani N, Boggio P, Pascual-Leone A. Diminishing risk-taking behavior by modulating activity in the prefrontal cortex: a direct current stimulation study. J Neurosci. 2007 Nov 14;27(46):12500–12505.
    1. Hecht D, Walsh V, Lavidor M. Transcranial direct current stimulation facilitates decision making in a probabilistic guessing task. J Neurosci. 2010 Mar 24;30(12):4241–4245.
    1. Brunoni AR, Valiengo L, Baccaro A, Zanao T, de Oliveira JF, Vieira GP, et al. Sertraline vs. electrical current therapy for treating depression clinical study - design, rationale and objectives. Contemp Clin Trials. Sep 17;
    1. Aldini G. Essai theorique et experimental sur le galvanisme. Paris 1804.
    1. Arndt R. Die electricitat in der psychiatrie. Arch Psychiat Nervenkrankh. 1869 Feb;:259–261.
    1. Kincses TZ, Antal A, Nitsche MA, Bartfai O, Paulus W. Facilitation of probabilistic classification learning by transcranial direct current stimulation of the prefrontal cortex in the human. Neuropsychologia. 2004;42(1):113–117.
    1. Stone DB, Tesche CD. Transcranial direct current stimulation modulates shifts in global/local attention. Neuroreport. 2009 Aug 5;20(12):1115–1119.
    1. Sparing R, Thimm M, Hesse MD, Kust J, Karbe H, Fink GR. Bidirectional alterations of interhemispheric parietal balance by non-invasive cortical stimulation. Brain. 2009 Jun 15;132(Pt 11):3011–3020.
    1. Bolognini N, Fregni F, Casati C, Olgiati E, Vallar G. Brain polarization of parietal cortex augments training-induced improvement of visual exploratory and attentional skills. Brain research. 2010 Aug 19;1349:76–89.
    1. Fertonani A, Rosini S, Cotelli M, Rossini PM, Miniussi C. Naming facilitation induced by transcranial direct current stimulation. Behav Brain Res. 2010 Apr 2;208(2):311–318.
    1. Sparing R, Dafotakis M, Meister IG, Thirugnanasambandam N, Fink GR. Enhancing language performance with non-invasive brain stimulation--a transcranial direct current stimulation study in healthy humans. Neuropsychologia. 2008 Jan 15;46(1):261–268.
    1. Priori A, Berardelli A, Rona S, Accornero N, Manfredi M. Polarization of the human motor cortex through the scalp. Neuroreport. 1998 Jul 13;9(10):2257–2260.
    1. Nitsche MA, Paulus W. Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol. 2000 Sep 15;527(Pt 3):633–639.
    1. Fritsch B, Reis J, Martinowich K, Schambra HM, Ji Y, Cohen LG, et al. Direct current stimulation promotes BDNF-dependent synaptic plasticity: potential implications for motor learning. Neuron. 2010 Apr 29;66(2):198–204.
    1. Nitsche MA, Liebetanz D, Antal A, Lang N, Tergau F, Paulus W. Modulation of cortical excitability by weak direct current stimulation--technical, safety and functional aspects. Suppl Clin Neurophysiol. 2003;56:255–276.
    1. Nitsche MA, Seeber A, Frommann K, Klein CC, Rochford C, Nitsche MS, et al. Modulating parameters of excitability during and after transcranial direct current stimulation of the human motor cortex. J Physiol. 2005 Oct 1;568(Pt 1):291–303.
    1. Kuo MF, Paulus W, Nitsche MA. Boosting focally-induced brain plasticity by dopamine. Cereb Cortex. 2008 Mar;18(3):648–651.
    1. Wagner T, Fregni F, Fecteau S, Grodzinsky A, Zahn M, Pascual-Leone A. Transcranial direct current stimulation: a computer-based human model study. Neuroimage. 2007 Apr 15;35(3):1113–1124.
    1. Miranda PC, Lomarev M, Hallett M. Modeling the current distribution during transcranial direct current stimulation. Clin Neurophysiol. 2006 Jul;117(7):1623–1629.
    1. Bikson M, Datta A, Elwassif M. Establishing safety limits for transcranial direct current stimulation. Clin Neurophysiol. 2009 Jun;120(6):1033–1034.
    1. Datta A, Bikson M, Fregni F. Transcranial direct current stimulation in patients with skull defects and skull plates: High-resolution computational FEM study of factors altering cortical current flow. Neuroimage. 2010 May 6;52(4):1268–1278.
    1. Boggio PS, Alonso-Alonso M, Mansur CG, Rigonatti SP, Schlaug G, Pascual-Leone A, et al. Hand function improvement with low-frequency repetitive transcranial magnetic stimulation of the unaffected hemisphere in a severe case of stroke. Am J Phys Med Rehabil. 2006 Nov;85(11):927–930.
    1. Iyer MB, Mattu U, Grafman J, Lomarev M, Sato S, Wassermann EM. Safety and cognitive effect of frontal DC brain polarization in healthy individuals. Neurology. 2005 Mar 8;64(5):872–875.
    1. Fecteau S, Pascual-Leone A, Zald DH, Liguori P, Theoret H, Boggio PS, et al. Activation of prefrontal cortex by transcranial direct current stimulation reduces appetite for risk during ambiguous decision making. J Neurosci. 2007 Jun 6;27(23):6212–6218.
    1. George MS, Aston-Jones G. Noninvasive techniques for probing neurocircuitry and treating illness: vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) Neuropsychopharmacology. 2010 Jan;35(1):301–316.
    1. Fregni F, Pascual-Leone A. Technology insight: noninvasive brain stimulation in neurology-perspectives on the therapeutic potential of rTMS and tDCS. Nat Clin Pract Neurol. 2007 Jul;3(7):383–393.
    1. Nitsche MA, Boggio PS, Fregni F, Pascual-Leone A. Treatment of depression with transcranial direct current stimulation (tDCS): a review. Exp Neurol. 2009 Sep;219(1):14–19.
    1. Brunoni AR, Tadini L, Fregni F. Changes in clinical trials methodology over time: a systematic review of six decades of research in psychopharmacology. PLoS One. 2010;5(3):e9479.
    1. Zhang X, Liu K, Sun J, Zheng Z. Safety and feasibility of repetitive transcranial magnetic stimulation (rTMS) as a treatment for major depression during pregnancy. Arch Womens Ment Health. 2010 Aug;13(4):369–370.
    1. Bolognini N, Pascual-Leone A, Fregni F. Using non-invasive brain stimulation to augment motor training-induced plasticity. J Neuroeng Rehabil. 2009;6:8.
    1. Zaghi S, Acar M, Hultgren B, Boggio PS, Fregni F. Noninvasive Brain Stimulation with Low-Intensity Electrical Currents: Putative Mechanisms of Action for Direct and Alternating Current Stimulation. Neuroscientist. 2009 Dec;:29.
    1. Nitsche MA, Cohen LG, Wassermann EM, Priori A, Lang N, Antal A, et al. Transcranial direct current stimulation: State of the art 2008 BRAIN STIMULATION. 2008;1(3):206–223.
    1. Priori A, Hallett M, Rothwell JC. Repetitive transcranial magnetic stimulation or transcranial direct current stimulation? Brain Stimul. 2009 Oct;2(4):241–245.
    1. Bindman LJ, Lippold OC, Redfearn JW. Relation between the Size and Form of Potentials Evoked by Sensory Stimulation and the Background Electrical Activity in the Cerebral Cortex of the Rat. J Physiol. 1964 May;171:1–25.
    1. Purpura DP, McMurtry JG. Intracellular Activities and Evoked Potential Changes during Polarization of Motor Cortex. J Neurophysiol. 1965 Jan 28;:166–185.
    1. Creutzfeldt OD, Fromm GH, Kapp H. Influence of transcortical d-c currents on cortical neuronal activity. Exp Neurol. 1962 Jun 5;:436–452.
    1. Bindman LJ, Lippold OC, Redfearn JW. 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. 1964 Aug 172;:369–382.
    1. Jefferys JG. Influence of electric fields on the excitability of granule cells in guinea-pig hippocampal slices. The Journal of Physiology. 1981;319:143–152.
    1. Bikson M, Inoue M, Akiyama H, Deans JK, Fox JE, Miyakawa H, et al. Effects of uniform extracellular DC electric fields on excitability in rat hippocampal slices in vitro. The Journal of Physiology. 2004 May 15;557(Pt 1):175–190.
    1. Nitsche MA, Paulus W. Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans. Neurology. 2001 Nov 27;57(10):1899–1901.
    1. Liebetanz D, Nitsche MA, Tergau F, Paulus W. Pharmacological approach to the mechanisms of transcranial DC-stimulation-induced after-effects of human motor cortex excitability. Brain. 2002 Oct;125(Pt 10):2238–2247.
    1. Nitsche MA, Fricke K, Henschke U, Schlitterlau A, Liebetanz D, Lang N, et al. Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans. J Physiol. 2003 Nov 15;553(Pt 1):293–301.
    1. Stagg CJ, Best JG, Stephenson MC, O'Shea J, Wylezinska M, Kincses ZT, et al. Polarity-sensitive modulation of cortical neurotransmitters by transcranial stimulation. J Neurosci. 2009 Apr 22;29(16):5202–5206.
    1. Ardolino G, Bossi B, Barbieri S, Priori A. Non-synaptic mechanisms underlie the after-effects of cathodal transcutaneous direct current stimulation of the human brain. J Physiol. 2005 Oct 15;568(Pt 2):653–663.
    1. Cogiamanian F, Vergari M, Pulecchi F, Marceglia S, Priori A. Effect of spinal transcutaneous direct current stimulation on somatosensory evoked potentials in humans. Clin Neurophysiol. 2008 Nov;119(11):2636–2640.
    1. Rango M, Cogiamanian F, Marceglia S, Barberis B, Arighi A, Biondetti P, et al. Myoinositol content in the human brain is modified by transcranial direct current stimulation in a matter of minutes: a 1H-MRS study. Magn Reson Med. 2008 Oct;60(4):782–789.
    1. Boros K, Poreisz C, Munchau A, Paulus W, Nitsche MA. Premotor transcranial direct current stimulation (tDCS) affects primary motor excitability in humans. Eur J Neurosci. 2008 Mar;27(5):1292–1300.
    1. Lang N, Siebner HR, Ward NS, Lee L, Nitsche MA, Paulus W, et al. How does transcranial DC stimulation of the primary motor cortex alter regional neuronal activity in the human brain? Eur J Neurosci. 2005 Jul;22(2):495–504.
    1. Parra LC, Bikson M. Model of the effect of extracellular fields on spike time coherence; Conf Proc IEEE Eng Med Biol Soc; 2004. Jun, pp. 4584–4587.
    1. Deans JK, Powell AD, Jefferys JG. Sensitivity of coherent oscillations in rat hippocampus to AC electric fields. The Journal of Physiology. 2007 Sep 1;583(Pt 2):555–565.
    1. Frohlich F, McCormick DA. Endogenous electric fields may guide neocortical network activity. Neuron. 2010 Jul 15;67(1):129–143.
    1. Accornero N, Li Voti P, La Riccia M, Gregori B. Visual evoked potentials modulation during direct current cortical polarization. Exp Brain Res. 2007 Apr;178(2):261–261.
    1. Matsunaga K, Nitsche MA, Tsuji S, Rothwell JC. Effect of transcranial DC sensorimotor cortex stimulation on somatosensory evoked potentials in humans. Clin Neurophysiol. 2004 Feb;115(2):456–460.
    1. Antal A, Kincses TZ, Nitsche MA, Bartfai O, Paulus W. Excitability changes induced in the human primary visual cortex by transcranial direct current stimulation: direct electrophysiological evidence. Invest Ophthalmol Vis Sci. 2004 Feb;45(2):702–707.
    1. Galea JM, Jayaram G, Ajagbe L, Celnik P. Modulation of cerebellar excitability by polarity-specific noninvasive direct current stimulation. J Neurosci. 2009 Jul 15;29(28):9115–9122.
    1. Winkler T, Hering P, Straube A. Spinal DC stimulation in humans modulates post-activation depression of the H-reflex depending on current polarity. Clin Neurophysiol. 2010 Jun;121(6):957–961.
    1. Merzagora AC, Foffani G, Panyavin I, Mordillo-Mateos L, Aguilar J, Onaral B, et al. Prefrontal hemodynamic changes produced by anodal direct current stimulation. Neuroimage. 2010 Feb 1;49(3):2304–2310.
    1. Nitsche MA, Jaussi W, Liebetanz D, Lang N, Tergau F, Paulus W. Consolidation of human motor cortical neuroplasticity by D-cycloserine. Neuropsychopharmacology. 2004 Aug;29(8):1573–1578.
    1. Nitsche MA, Liebetanz D, Schlitterlau A, Henschke U, Fricke K, Frommann K, et al. GABAergic modulation of DC stimulation-induced motor cortex excitability shifts in humans. The European journal of neuroscience. 2004 May;19(10):2720–2726.
    1. Nitsche MA, Grundey J, Liebetanz D, Lang N, Tergau F, Paulus W. Catecholaminergic consolidation of motor cortical neuroplasticity in humans. Cereb Cortex. 2004 Nov;14(14):1240–1245.
    1. Kuo MF, Unger M, Liebetanz D, Lang N, Tergau F, Paulus W, et al. Limited impact of homeostatic plasticity on motor learning in humans. Neuropsychologia. 2008;46(8):2122–2128.
    1. Nitsche MA, Doemkes S, Karakose T, Antal A, Liebetanz D, Lang N, et al. Shaping the effects of transcranial direct current stimulation of the human motor cortex. J Neurophysiol. 2007 Apr;97(4):3109–3117.
    1. Monte-Silva K, Kuo MF, Thirugnanasambandam N, Liebetanz D, Paulus W, Nitsche MA. Dose-dependent inverted U-shaped effect of dopamine (D2-like) receptor activation on focal and nonfocal plasticity in humans. J Neurosci. 2009 May 13;29(19):6124–6131.
    1. Nitsche MA, Kuo MF, Karrasch R, Wachter B, Liebetanz D, Paulus W. Serotonin affects transcranial direct current-induced neuroplasticity in humans. Biological psychiatry. 2009 Sep 1;66(5):503–508.
    1. Antal A, Kincses TZ, Nitsche MA, Paulus W. Manipulation of phosphene thresholds by transcranial direct current stimulation in man. Exp Brain Res. 2003 Jun;150(3):375–378.
    1. Utz KS, Dimova V, Oppenlander K, Kerkhoff G. Electrified minds: Transcranial direct current stimulation (tDCS) and Galvanic Vestibular Stimulation (GVS) as methods of non-invasive brain stimulation in neuropsychology-A review of current data and future implications. Neuropsychologia. 2010 Jun 11;48(10):2789–2810.
    1. Williams JA, Pascual-Leone A, Fregni F. Interhemispheric modulation induced by cortical stimulation and motor training. Phys Ther. 2010 Mar;90(3):398–410.
    1. Mahmoudi H, Haghighi AB, Petramfar P, Jahanshahi S, Salehi Z, Fregni F. Transcranial direct current stimulation: Electrode montage in stroke. Disability and Rehabilitation. in press.
    1. Redfearn JW, Lippold OC, Costain R. A Preliminary Account of the Clinical Effects of Polarizing the Brain in Certain Psychiatric Disorders. Br J Psychiatry. 1964 Nov;110:773–785.
    1. Cogiamanian F, Vergari M, Ardolino G, Scelzo E, Ciocca M, Barbieri M, et al., editors. Effects of transcutaneous spinal cord direct current stimulation (tsDCS) on the lower limb nociceptive flexion reflex in humans. Neurological Sciences; Proceedings of the XLI Congress of the Italian Neurological Society.2010.
    1. Datta A, Rahman A, Scaturro J, Bikson M. Electrode montages for tDCS and weak transcranial electrical stimulation Role of "return" electrode's position and size. Clin Neurophysiol. in press.
    1. Moliadze V, Antal A, Paulus W. Electrode-distance dependent after-effects of transcranial direct and random noise stimulation with extracephalic reference electrodes. Clinical Neurophysiology. 2010 Jun 14;121(12):2165–2171.
    1. Datta A, Elwassif M, Battaglia F, Bikson M. Transcranial current stimulation focality using disc and ring electrode configurations: FEM analysis. J Neural Eng. 2008 Jun;5(2):163–174.
    1. Datta A, Bansal V, Diaz J, Patel J, Reato D, Bikson M. Gyri-precise head model of transcranial direct current stimulation: Improved spatial focality using a ring electrode versus conventional rectangular pad. Brain Stimulation. 2009;2(4):201–207.
    1. Sadleir RJ, Vannorsdall TD, Schretlen DJ, Gordon B. Transcranial direct current stimulation (tDCS) in a realistic head model. Neuroimage. 2010 Jul 15;51(4):1310–1318.
    1. Minhas P, Bansal V, Patel J, Ho JS, Diaz J, Datta A, et al. Electrodes for high-definition transcutaneous DC stimulation for applications in drug delivery and electrotherapy, including tDCS. Journal of Neuroscience Methods. 2010 Jul 15;190(2):188–197.
    1. Faria P, Leal A, Miranda PC. Comparing different electrode configurations using the 10-10 international system in tDCS: a finite element model analysis. Conf Proc IEEE Eng Med Biol Soc. 2009;2009:1596–1599.
    1. Suh HS, Kim SH, Lee WH, Kim TS. Realistic simulation of transcranial direct current stimulation via 3-d high-resolution finite element analysis: Effect of tissue anisotropy. Conf Proc IEEE Eng Med Biol Soc. 2009;2009:638–641.
    1. Liebetanz D, Koch R, Mayenfels S, Konig F, Paulus W, Nitsche MA. Safety limits of cathodal transcranial direct current stimulation in rats. Clin Neurophysiol. 2009 Jun;120(6):1161–1167.
    1. Fregni F, Liebetanz D, Monte-Silva KK, Oliveira MB, Santos AA, Nitsche MA, et al. Effects of transcranial direct current stimulation coupled with repetitive electrical stimulation on cortical spreading depression. Exp Neurol. 2007 Mar;204(1):462–466.
    1. Palm U, Keeser D, Schiller C, Fintescu Z, Reisinger E, Nitsche M, et al. Skin lesions after treatment with transcranial direct current stimulation (tDCS) Brain Stimul. 2008 Oct;1(4):386–387.
    1. Durand S, Fromy B, Bouye P, Saumet JL, Abraham P. Vasodilatation in response to repeated anodal current application in the human skin relies on aspirin-sensitive mechanisms. J Physiol. 2002 Apr 1;540(Pt 1):261–269.
    1. Poreisz C, Boros K, Antal A, Paulus W. Safety aspects of transcranial direct current stimulation concerning healthy subjects and patients. Brain Res Bull. 2007 May 30;72(4–6):208–214.
    1. Tadini L, El-Nazer R, Brunoni AR, Williams J, Carvas M, Boggio PS, et al. Cognitive, mood and EEG effects of noninvasive cortical stimulation with weak electrical currents. The Journal of Electroconvulsive Therapy. 2010
    1. Nitsche MA, Liebetanz D, Lang N, Antal A, Tergau F, Paulus W. Safety criteria for transcranial direct current stimulation (tDCS) in humans. Clin Neurophysiol. 2003 Nov;114(11):2220–2222. author reply 2–3.
    1. Fregni F, Boggio PS, Nitsche MA, Rigonatti SP, Pascual-Leone A. Cognitive effects of repeated sessions of transcranial direct current stimulation in patients with depression. Depress Anxiety. 2006;23(8):482–484.
    1. Boggio PS, Nunes A, Rigonatti SP, Nitsche MA, Pascual-Leone A, Fregni F. Repeated sessions of noninvasive brain DC stimulation is associated with motor function improvement in stroke patients. Restor Neurol Neurosci. 2007;25(2):123–129.
    1. Loo C, Martin D, Pigot M, Arul-Anandam P, Mitchell P, Sachdev P. Transcranial Direct Current Stimulation Priming of Therapeutic Repetitive Transcranial Magnetic Stimulation: A Pilot Study. J ECT. 2009 May 12;
    1. Fregni F, Thome-Souza S, Nitsche MA, Freedman SD, Valente KD, Pascual-Leone A. A controlled clinical trial of cathodal DC polarization in patients with refractory epilepsy. Epilepsia. 2006 Feb;47(2):335–342.
    1. Arul-Anandam AP, Loo C, Mitchell P. Induction of hypomanic episode with transcranial direct current stimulation. J ECT. 2010 Mar;26(1):68–69.
    1. Baccaro A, Brunoni AR, Bensenor IM, Fregni F. Hypomanic episode in unipolar depression during transcranial direct current stimulation. Acta Neuropsychiatrica. 2010;22(6):316–318.
    1. Brunoni AR, Valiengo L, Zanao T, Oliveira J, Bensenor IM, Fregni F. Manic psychosis following transcranial direct current stimulation and sertraline. The Journal of Neuropsychiatry and Clinical Neurosciences. in press.
    1. Miranda PC, Faria P, Hallett M. What does the ratio of injected current to electrode area tell us about current density in the brain during tDCS? Clin Neurophysiol. 2009 Jun;120(6):1183–1187.
    1. Fregni F, Boggio PS, Valle AC, Otachi P, Thut G, Rigonatti SP, et al. Homeostatic effects of plasma valproate levels on corticospinal excitability changes induced by 1Hz rTMS in patients with juvenile myoclonic epilepsy. Clin Neurophysiol. 2006 Jun;117(6):1217–1227.
    1. Ziemann U. Pharmacology of TMS. Suppl Clin Neurophysiol. 2003;56:226–231.
    1. Bajwa S, Bermpohl F, Rigonatti SP, Pascual-Leone A, Boggio PS, Fregni F. Impaired interhemispheric interactions in patients with major depression. J Nerv Ment Dis. 2008 Sep;196(9):671–677.
    1. Soubasi E, Chroni E, Gourzis P, Zisis A, Beratis S, Papathanasopoulos P. Cortical motor neurophysiology of patients with schizophrenia: a study using transcranial magnetic stimulation. Psychiatry research. 2010 Apr 30;176(2–3):132–136.
    1. Mhalla A, de Andrade DC, Baudic S, Perrot S, Bouhassira D. Alteration of cortical excitability in patients with fibromyalgia. Pain. 2010 Jun;149(3):495–500.
    1. Brighina F, Palermo A, Fierro B. Cortical inhibition and habituation to evoked potentials: relevance for pathophysiology of migraine. J Headache Pain. 2009 Apr;10(2):77–84.
    1. Chaieb L, Antal A, Paulus W. Gender-specific modulation of short-term neuroplasticity in the visual cortex induced by transcranial direct current stimulation. Vis Neurosci. 2008 Jan-Feb;25(1):77–81.
    1. Ferri R, Del Gracco S, Elia M, Musumeci SA. Age-related changes of cortical excitability in subjects with sleep-enhanced centrotemporal spikes: a somatosensory evoked potential study. Clin Neurophysiol. 2000 Apr;111(4):591–599.
    1. Lang N, Hasan A, Sueske E, Paulus W, Nitsche MA. Cortical hypoexcitability in chronic smokers? A transcranial magnetic stimulation study. Neuropsychopharmacology. 2008 Sep;33(10):2517–2523.
    1. Monte-Silva K, Liebetanz D, Grundey J, Paulus W, Nitsche MA. Dosage-dependent non-linear effect of L-dopa on human motor cortex plasticity. J Physiol. 2010 Sep 15;588(Pt 18):3415–3424.
    1. Ohn SH, Park CI, Yoo WK, Ko MH, Choi KP, Kim GM, et al. Time-dependent effect of transcranial direct current stimulation on the enhancement of working memory. Neuroreport. 2008 Jan 8;19(1):43–47.
    1. Boggio PS, Ferrucci R, Rigonatti SP, Covre P, Nitsche M, Pascual-Leone A, et al. Effects of transcranial direct current stimulation on working memory in patients with Parkinson's disease. J Neurol Sci. 2006 Nov 1;249(1):31–38.
    1. Froc DJ, Chapman CA, Trepel C, Racine RJ. Long-term depression and depotentiation in the sensorimotor cortex of the freely moving rat. J Neurosci. 2000 Jan 1;20(1):438–445.
    1. Monte-Silva KK, Kuo MF, Liebetanz D, Paulus W, Nitsche MA. Shaping the optimal repetition interval for cathodal transcranial direct current stimulation (tDCS) J Neurophysiol. 2010 Jan 27;103(4):1735–1740.
    1. Siebner HR, Lang N, Rizzo V, Nitsche MA, Paulus W, Lemon RN, et al. Preconditioning of low-frequency repetitive transcranial magnetic stimulation with transcranial direct current stimulation: evidence for homeostatic plasticity in the human motor cortex. J Neurosci. 2004 Mar 31;24(13):3379–3385.
    1. Brunoni AR, Fregni F. Clinical Trial Design in Noninvasive Brain Stimulation Psychiatric Research. International Journal of Methods in Psychiatry Research. (in press)
    1. Gandiga PC, Hummel FC, Cohen LG. Transcranial DC stimulation (tDCS): a tool for double-blind sham-controlled clinical studies in brain stimulation. Clin Neurophysiol. 2006 Apr;117(4):845–850.
    1. Dundas JE, Thickbroom GW, Mastaglia FL. Perception of comfort during transcranial DC stimulation: effect of NaCl solution concentration applied to sponge electrodes. Clin Neurophysiol. 2007 May;118(5):1166–1170.
    1. Freedman B. Equipoise and the ethics of clinical research. N Engl J Med. 1987 Jul 16;317(3):141–145.
    1. Schutter DJ. Nosce te ipsum: On the efficacy of transcranial magnetic stimulation in major depressive disorder. Biol Psychiatry. 2010 Mar 1;67(5):e27. author reply e9.
    1. Yu E, Lurie P. Transcranial magnetic stimulation not proven effective. Biol Psychiatry. 2010 Jan 15;67(2):e13. author reply e5–7.
    1. D'Agostino RB., Jr Debate: The slippery slope of surrogate outcomes. Curr Control Trials Cardiovasc Med. 2000;1(2):76–78.
    1. Kobayashi M, Pascual-Leone A. Transcranial magnetic stimulation in neurology. Lancet Neurology. 2003 Mar;2(3):145–156.
    1. Pascual-Marqui RD, Esslen M, Kochi K, Lehmann D. Functional imaging with low-resolution brain electromagnetic tomography (LORETA): a review. Methods Find Exp Clin Pharmacol. 2002;24(Suppl C):91–95.
    1. May A, Hajak G, Ganssbauer S, Steffens T, Langguth B, Kleinjung T, et al. Structural brain alterations following 5 days of intervention: dynamic aspects of neuroplasticity. Cerebral Cortex. 2007 Jan;17(1):205–210.
    1. Kriegeskorte N, Lindquist MA, Nichols TE, Poldrack RA, Vul E. Everything you never wanted to know about circular analysis, but were afraid to ask. J Cereb Blood Flow Metab. 2010 Jun 23;30(9):1551–1557.
    1. Gelenberg AJ, Thase ME, Meyer RE, Goodwin FK, Katz MM, Kraemer HC, et al. The history and current state of antidepressant clinical trial design: a call to action for proof-of-concept studies. J Clin Psychiatry. 2008 Oct;69(10):1513–1528.
    1. Brunoni AR, Lopes M, Fregni F. A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: implications for the role of neuroplasticity in depression. Int J Neuropsychopharmacol. 2008 Dec;11(8):1169–1180.
    1. Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, et al. A meta-analysis of cytokines in major depression. Biol Psychiatry. 2010 Mar 1;67(5):446–457.
    1. Quinones MP, Kaddurah-Daouk R. Metabolomics tools for identifying biomarkers for neuropsychiatric diseases. Neurobiol Dis. 2009 Aug;35(2):165–176.
    1. Marques AH, Cizza G, Sternberg E. [Brain-immune interactions and implications in psychiatric disorders] Rev Bras Psiquiatr. 2007 May;29(Suppl 1):S27–S32.
    1. Maes M, Yirmyia R, Noraberg J, Brene S, Hibbeln J, Perini G, et al. The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis. 2009 Mar;24(1):27–53.
    1. Spencer-Smith M, Anderson V. Healthy and abnormal development of the prefrontal cortex. Dev Neurorehabil. 2009;12(5):279–297.
    1. Frye RE, Rotenberg A, Ousley M, Pascual-Leone A. Transcranial magnetic stimulation in child neurology: current and future directions. J Child Neurol. 2008 Jan;23(1):79–96.
    1. Fumagalli M, Vergari M, Pasqualetti P, Marceglia S, Mameli F, Ferrucci R, et al. Brain switches utilitarian behavior: does gender make the difference? PLoS One. 2010;5(1):e8865.
    1. Luber B, Fisher C, Appelbaum PS, Ploesser M, Lisanby SH. Non-invasive brain stimulation in the detection of deception: scientific challenges and ethical consequences. Behav Sci Law. 2009;27(2):191–208.
    1. Mameli F, Mrakic-Sposta S, Vergari M, Fumagalli M, Macis M, Ferrucci R, et al. Dorsolateral prefrontal cortex specifically processes general - but not personal - knowledge deception: Multiple brain networks for lying. Behav Brain Res. 2010 Aug 25;211(2):164–168.
    1. Boggio PS, Campanha C, Valasek CA, Fecteau S, Pascual-Leone A, Fregni F. Modulation of decision-making in a gambling task in older adults with transcranial direct current stimulation. Eur J Neurosci. 2010 Feb;31(3):593–597.
    1. Reis J, Robertson E, Krakauer JW, Rothwell J, Marshall L, Gerloff C, et al. Consensus: "Can tDCS and TMS enhance motor learning and memory formation?". Brain Stimul. 2008 Oct;1(4):363–369.
    1. Anonymous. [cited 2010 September 25th];2010 Available from: .

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe