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Transcranial Direct Current Stimulation for the Treatment of Depression: a Review of the Candidate Mechanisms of Action

  • Mood and Anxiety Disorders (C Harmer, Section Editor)
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Abstract

Purpose of Review

Numerous studies published in the last 10 years indicate that repeated administration of prefrontal transcranial direct current stimulation (tDCS) is a potential effective treatment for major depressive disorder (MDD). However, the mechanisms of action are unclear and methods of patient selection for clinical trials are limited. This review seeks to examine the potential neural and cognitive mechanisms of action of tDCS in the treatment of MDD, to aid patient selection for future clinical trials.

Recent Findings

Cognitive measures of tDCS efficacy in the treatment of MDD have begun to be examined over the past 5 years. Baseline measures of working memory and letter fluency have been shown to predict treatment response. In addition, tDCS reduced cognitive deficits induced by stress, suggesting a protective mechanism.

Summary

Baseline measures of working memory and letter fluency may aid patient selection in future clinical trials of tDCS. In addition, reduction of stress responsivity may be a key mechanism of action for tDCS in clinical groups and merits further investigation, acutely and post-treatment.

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Notes

  1. MEPs elicited by transcranial magnetic stimulation (TMS) of the motor cortex.

  2. Cathodal stimulation also resulted in correlated (smaller) reductions in GABA, though the overall neurochemical effect is inhibitory.

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Pascual-Leone A, Wagner T. A brief summary of the history of noninvasive brain stimulation. Annu Rev Biomed Eng. 2007;9(1):527–65. https://doi.org/10.1146/annurev.bioeng.9.061206.133100.

    Article  PubMed  Google Scholar 

  2. Aldini G. Essai theorique et experimental sur le galvanisme, avec une serie d’experiences faites en presence des commissaires de l’Institut national de France, et en divers amphitheatres anatomiques de Londres, par Jean Aldini... Avec planches. De l’imprimerie de Fournier Fils; 1804.

  3. Bindman LJ, Lippold OCJ, Redfearn JWT. 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 Wiley-Blackwell. 1964;172(3):369.

    CAS  Google Scholar 

  4. Purpura DP, McMurtry JG. Intracellular activities and evoked potential changes during polarization of motor cortex. J Neurophysiol Am Physiological Soc. 1965;28(1):166–85. https://doi.org/10.1152/jn.1965.28.1.166.

    Article  CAS  Google Scholar 

  5. Walsh V, Rushworth M. A primer of magnetic stimulation as a tool for neuropsychology. Neuropsychologia PERGAMON PRESS. 1999;37:125–36.

    CAS  Google Scholar 

  6. Pascual-Leone A. Transcranial magnetic stimulation: studying the brain—behaviour relationship by induction of “virtual lesions”. Philos Trans R Soc B Biol Sci The Royal Society. 1999;354(1387):1229–38. https://doi.org/10.1098/rstb.1999.0476.

    Article  CAS  Google Scholar 

  7. O’Reardon JP, Solvason HB, Janicak PG, Sampson S, Isenberg KE, Nahas Z, et al. Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial. Biol Psychiatry Elsevier. 2007;62(11):1208–16. https://doi.org/10.1016/j.biopsych.2007.01.018.

    Article  Google Scholar 

  8. Nahas Z, Teneback CC, Kozel A, Speer AM, DeBrux C, Molloy M, et al. Brain effects of TMS delivered over prefrontal cortex in depressed adults: role of stimulation frequency and coil–cortex distance. J Neuropsychiatry Clin Neurosci Am Neuropsych Assoc. 2001;13(4):459–70. https://doi.org/10.1176/jnp.13.4.459.

    Article  CAS  Google Scholar 

  9. Teneback CC, Nahas Z, Speer AM, Molloy M, Stallings LE, Spicer KM, et al. Changes in prefrontal cortex and paralimbic activity in depression following two weeks of daily left prefrontal TMS. J Neuropsychiatry Clin Neurosci United States. 1999;11(4):426–35.

    CAS  Google Scholar 

  10. Speer AM, Kimbrell TA, Wassermann EM, D Repella J, Willis MW, Herscovitch P, et al. Opposite effects of high and low frequency rTMS on regional brain activity in depressed patients. Biol Psychiatry. United States. 2000 Dec;48(12):1133–41. https://doi.org/10.1016/S0006-3223(00)01065-9.

    Article  CAS  Google Scholar 

  11. Ohnishi T, Matsuda H, Imabayashi E, Okabe S, Takano H, Arai N, et al. rCBF changes elicited by rTMS over DLPFC in humans. Suppl Clin Neurophysiol Netherlands. 2004;57:715–20. https://doi.org/10.1016/S1567-424X(09)70412-X.

    Article  Google Scholar 

  12. George MS, Wassermann EM, Williams WA, Callahan A, Ketter TA, Basser P, et al. Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression. Neuroreport LWW. 1995;6(14):1853–6. https://doi.org/10.1097/00001756-199510020-00008.

    Article  CAS  Google Scholar 

  13. George MS, Schlaepfer T, Padberg F, Fitzgerald PB. Brain stimulation treatments for depression. World J Biol Psychiatry Taylor & Francis. 2014;15(2):167–8. https://doi.org/10.3109/15622975.2013.869619.

    Article  Google Scholar 

  14. Schrader LM, Stern JM, Koski L, Nuwer MR, Engel J. Seizure incidence during single-and paired-pulse transcranial magnetic stimulation (TMS) in individuals with epilepsy. Clin Neurophysiol Elsevier. 2004;115(12):2728–37. https://doi.org/10.1016/j.clinph.2004.06.018.

    Article  Google Scholar 

  15. 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 [Internet] England. 2003 Nov;553(1):293–301. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2343495&tool=pmcentrez&rendertype=abstract

  16. Nitsche MA, Jaussi W, Liebetanz D, Lang N, Tergau F, Paulus W. Consolidation of human motor cortical neuroplasticity by D-cycloserine. Neuropsychopharmacology United States. 2004 Aug;29(8):1573–8. https://doi.org/10.1038/sj.npp.1300517.

    Article  CAS  Google Scholar 

  17. 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 [Internet]. England. 2002;125(10):2238–47. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12244081

    Google Scholar 

  18. Monte-Silva K, Kuo M-F, Hessenthaler S, Fresnoza S, Liebetanz D, Paulus W, et al. Induction of late LTP-like plasticity in the human motor cortex by repeated non-invasive brain stimulation. Brain Stimul United States. 2013 May;6(3):424–32. https://doi.org/10.1016/j.brs.2012.04.011.

    Article  Google Scholar 

  19. Nitsche MA, Paulus W. Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans. Neurology. 2001;57(10):1899–901. https://doi.org/10.1212/WNL.57.10.1899.

    Article  CAS  PubMed  Google Scholar 

  20. 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 [Internet]. 2009;29(16):5202–6. https://doi.org/10.1523/JNEUROSCI.4432-08.2009.

    Article  CAS  PubMed  Google Scholar 

  21. Iversen L, Iversen S, Bloom FE, Roth RH. Introduction to neuropsychopharmacology: Oxford University Press; 2008.

  22. Nitsche MA, Schauenburg A, Lang N, Liebetanz D, Exner C, Paulus W, et al. Facilitation of implicit motor learning by weak transcranial direct current stimulation of the primary motor cortex in the human. J Cogn Neurosci MIT Press. 2003;15(4):619–26. https://doi.org/10.1162/089892903321662994.

    Article  Google Scholar 

  23. Fregni F, Boggio PS, Mansur CG, Wagner T, Ferreira MJL, Lima MC, et al. Transcranial direct current stimulation of the unaffected hemisphere in stroke patients. Neuroreport. 2005;16(14):1551–5. https://doi.org/10.1097/01.wnr.0000177010.44602.5e.

    Article  PubMed  Google Scholar 

  24. Krause B, Márquez-Ruiz J, Cohen KR. The effect of transcranial direct current stimulation: a role for cortical excitation/inhibition balance? Front Hum Neurosci [Internet]. 2013;7:602. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3781319&tool=pmcentrez&rendertype=abstract

    Google Scholar 

  25. Palm U, Hasan A, Strube W, Padberg F. tDCS for the treatment of depression: a comprehensive review. Eur Arch Psychiatry Clin Neurosci. 2016 Dec;266(8):681–94. https://doi.org/10.1007/s00406-016-0674-9.

    Article  PubMed  Google Scholar 

  26. •• Kekic M, Boysen E, Campbell IC, Schmidt U. A systematic review of the clinical efficacy of transcranial direct current stimulation (tDCS) in psychiatric disorders. J Psychiatr Res. 2016;74:70–86. Most up-to-date review of RCTs of tDCS in depression .

  27. •• Brunoni A, Moffa A, Fregni F, Palm U, Padberg F, Blumberger DM, et al. Transcranial direct current stimulation for major depression: a meta-analysis of individual patient data. Biol Psychiatry. Elsevier Science Inc. 2015;77(9):22S–S. Novel meta-analytic approach to reviewing tDCS data.

  28. Brunoni AR, Valiengo L, Baccaro A, Zanao TA, de Oliveira JF, Goulart A, et al. The sertraline vs. electrical current therapy for treating depression clinical study: results from a factorial, randomized, controlled trial. JAMA Psychiatry. United States. 2013;70(4):383–91.

    Article  CAS  Google Scholar 

  29. •• Brunoni AR, Moffa AH, Sampaio-Junior B, Borrione L, Moreno ML, Fernandes RA, et al. Trial of electrical direct-current therapy versus escitalopram for depression. N Engl J Med. 2017;376(26):2523–33. Largest tDCS RCT for depression to date.

  30. M a M, Romanski LM, LeDoux JE. Extinction of emotional learning: contribution of medial prefrontal cortex. Neurosci Lett. 1993;163:109–13.

    Article  Google Scholar 

  31. Maroun M, Kavushansky A, Holmes A, Wellman C, Motanis H. Enhanced extinction of aversive memories by high-frequency stimulation of the rat infralimbic cortex. PLoS One United States. 2012;7(5):1–8.

    Google Scholar 

  32. Herry C, Garcia R. Prefrontal Cortex long-term potentiation, but not long-term depression, is associated with the maintenance of extinction of learned fear in mice. J Neurosci. Soc Neuroscience. 2002;22(2):577–83.

    CAS  Google Scholar 

  33. Quirk GJ, Likhtik E, Pelletier JG, Pare D. Stimulation of medial prefrontal cortex decreases the responsiveness of central amygdala output neurons. J Neurosci United States. 2003;23(25):8800–7.

    CAS  Google Scholar 

  34. Drevets WC. Prefrontal cortical-amygdalar metabolism in major depression. Ann N Y Acad Sci. 1999;877:614–37.

    Article  CAS  PubMed  Google Scholar 

  35. Paulus MP, Feinstein JS, Castillo G, Simmons AN, Stein MB. Dose-dependent decrease of activation in bilateral amygdala and insula by lorazepam during emotion processing. Arch Gen Psychiatry American Medical Association. 2005;62(3):282–8. https://doi.org/10.1001/archpsyc.62.3.282.

    Article  CAS  Google Scholar 

  36. Furmark T, Tillfors M, Marteinsdottir I, Fischer H, Pissiota A, Långström B, et al. Common changes in cerebral blood flow in patients with social phobia treated with citalopram or cognitive-behavioral therapy. Arch Gen Psychiatry. American Medical Association. 2002;59(5):425–33. https://doi.org/10.1001/archpsyc.59.5.425.

    Article  Google Scholar 

  37. Davidson RJ, Pizzagalli D, Nitschke JB, Putnam K. Depression: perspectives from affective neuroscience. Annu Rev Psychol. 2002;53(1):545–74. https://doi.org/10.1146/annurev.psych.53.100901.135148.

    Article  PubMed  Google Scholar 

  38. Harmer CJ, Goodwin GM, Cowen PJ. Why do antidepressants take so long to work? A cognitive neuropsychological model of antidepressant drug action. Br J Psychiatry. 2009;195(2):102–8. https://doi.org/10.1192/bjp.bp.108.051193.

    Article  PubMed  Google Scholar 

  39. Harmer CJ, Hill SA, Taylor MJ, Cowen PJ, Goodwin GM. Toward a neuropsychological theory of antidepressant drug action: increase in positive emotional bias after potentiation of norepinephrine activity. Am J Psychiatry. 2003;160(5):990–2. https://doi.org/10.1176/appi.ajp.160.5.990.

    Article  PubMed  Google Scholar 

  40. Tranter R, Bell D, Gutting P, Harmer C, Healy D, Anderson IM. The effect of serotonergic and noradrenergic antidepressants on face emotion processing in depressed patients. J Affect Disord [Internet]. Elsevier B.V. 2009;118(1–3):87–93. https://doi.org/10.1016/j.jad.2009.01.028.

    Article  CAS  Google Scholar 

  41. Reinecke A, Waldenmaier L, Cooper MJ, Harmer CJ. Changes in automatic threat processing precede and predict clinical changes with exposure-based cognitive-behavior therapy for panic disorder. Biol Psychiatry United States. 2013;73(11):1064–70. https://doi.org/10.1016/j.biopsych.2013.02.005.

    Article  Google Scholar 

  42. Remue J, Baeken C, De Raedt R. Does a single neurostimulation session really affect mood in healthy individuals? A systematic review. Neuropsychologia. 2016 May;85:184–98.

    Article  PubMed  Google Scholar 

  43. Tortella G, PML S, Moreno ML, Veronezi BP, Brunoni AR. Does non-invasive brain stimulation improve cognition in major depressive disorder? A systematic review. CNS Neurol Disord Targets. 2014;13(10):1759–69.

    Article  Google Scholar 

  44. De Raedt R, Vanderhasselt M-A, Baeken C. Neurostimulation as an intervention for treatment resistant depression: from research on mechanisms towards targeted neurocognitive strategies. Clin Psychol Rev. 2015;41(SI):61–9.

    Article  PubMed  Google Scholar 

  45. Liu W, Leng YS, Zou XH, Cheng ZQ, Yang W, Li BJ. Affective processing in non-invasive brain stimulation over prefrontal cortex. Front Hum Neurosci. 2017 Sep;11 https://doi.org/10.3389/fnhum.2017.00439.

  46. McClintock S, Martin D, Alonzo A, Lisanby S, Husain M, Aaronson S, et al. Neurocognitive effects of transcranial direct current stimulation (tDCS) in unipolar and bipolar depression: results from an international randomized controlled trial. Biol Psychiatry. 2017;81(10, S):S261.

    Article  Google Scholar 

  47. Brunoni AR, Vanderhasselt M-A. Working memory improvement with non-invasive brain stimulation of the dorsolateral prefrontal cortex: a systematic review and meta-analysis. Brain Cogn. 2014 Apr;86:1–9. https://doi.org/10.1016/j.bandc.2014.01.008.

    Article  PubMed  Google Scholar 

  48. Hill AT, Fitzgerald PB, Hoy KE. Effects of anodal transcranial direct current stimulation on working memory: a systematic review and meta-analysis of findings from healthy and neuropsychiatric populations. Brain Stimul Elsevier. 2016;9(2):197–208. https://doi.org/10.1016/j.brs.2015.10.006.

    Article  Google Scholar 

  49. Liu A, Bryant A, Jefferson A, Friedman D, Minhas P, Barnard S, et al. Exploring the efficacy of a 5-day course of transcranial direct current stimulation (TDCS) on depression and memory function in patients with well-controlled temporal lobe epilepsy. Epilepsy Behav. 2016 Feb;55:11–20. https://doi.org/10.1016/j.yebeh.2015.10.032.

    Article  PubMed  Google Scholar 

  50. Nikolin S, Boonstra TW, Loo CK, Martin D. Combined effect of prefrontal transcranial direct current stimulation and a working memory task on heart rate variability. PLoS One. 2017 Aug;12(8):e0181833. https://doi.org/10.1371/journal.pone.0181833.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Martin DM, Liu R, Alonzo A, Green M, Player MJ, Sachdev P, et al. Can transcranial direct current stimulation enhance outcomes from cognitive training? A randomized controlled trial in healthy participants. Int J Neuropsychopharmacol. 2013 Oct;16(9):1927–36. https://doi.org/10.1017/S1461145713000539.

    Article  PubMed  Google Scholar 

  52. Moreno ML, Vanderhasselt M-A, Carvalho AF, Moffa AH, Lotufo PA, Bensenor IM, et al. Effects of acute transcranial direct current stimulation in hot and cold working memory tasks in healthy and depressed subjects. Neurosci Lett Ireland. 2015 Mar;591:126–31. https://doi.org/10.1016/j.neulet.2015.02.036.

    Article  CAS  Google Scholar 

  53. Schroeder PA, Ehlis A-C, Wolkenstein L, Fallgatter AJ, Plewnia C. Emotional distraction and bodily reaction: modulation of autonomous responses by anodal tDCS to the prefrontal cortex. Front Cell Neurosci. 2015 Dec;9 https://doi.org/10.3389/fncel.2015.00482.

  54. Bogdanov M, Schwabe L. Transcranial stimulation of the dorsolateral prefrontal cortex prevents stress-induced working memory deficits. J Neurosci. 2016 Jan;36(4):1429–37. https://doi.org/10.1523/JNEUROSCI.3687-15.2016.

    Article  CAS  PubMed  Google Scholar 

  55. Martin DM, Chan H-N, Alonzo A, Green MJ, Mitchell PB, Loo CK. Transcranial direct current stimulation to enhance cognition in euthymic bipolar disorder. Bipolar Disord. 2015 Dec;17(8):849–58. https://doi.org/10.1111/bdi.12350.

    Article  PubMed  Google Scholar 

  56. Bajbouj M, Padberg F. A perfect match: noninvasive brain stimulation and psychotherapy. Eur Arch Psychiatry Clin Neurosci. 2014;264(1):S27–33.

    Article  PubMed  Google Scholar 

  57. Pope PA, Brenton JW, Miall RC. Task-specific facilitation of cognition by anodal transcranial direct current stimulation of the prefrontal cortex. Cereb Cortex. 2015 Nov;25(11):4551–8. https://doi.org/10.1093/cercor/bhv094.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Salehinejad MA, Ghanavai E, Rostami R, Nejati V. Cognitive control dysfunction in emotion dysregulation and psychopathology of major depression (MD): evidence from transcranial brain stimulation of the dorsolateral prefrontal cortex (DLPFC). J Affect Disord. 2017 Mar;210:241–8. https://doi.org/10.1016/j.jad.2016.12.036.

    Article  PubMed  Google Scholar 

  59. Segrave RA, Arnold S, Hoy K, Fitzgerald PB. Concurrent cognitive control training augments the antidepressant efficacy of tDCS: A pilot study. Brain Stimul [Internet]. Elsevier Ltd. 2014;7(2):325–31. https://doi.org/10.1016/j.brs.2013.12.008.

    Article  CAS  Google Scholar 

  60. Vanderhasselt MA, De Raedt R, Brunoni AR, Campanhã C, Baeken C, Remue J, et al. tDCS over the left prefrontal cortex enhances cognitive control for positive affective stimuli. PLoS One. 2013;8(5):4–9.

    Article  Google Scholar 

  61. Plewnia C, Schroeder PA, Kunze R, Faehling F, Wolkenstein L. Keep calm and carry on: improved frustration tolerance and processing speed by transcranial direct current stimulation (tDCS). PLoS One. 2015 Apr;10(4):e0122578. https://doi.org/10.1371/journal.pone.0122578.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Kelley NJ, Hortensius R, Harmon-Jones E. When anger leads to rumination: induction of relative right frontal cortical activity with transcranial direct current stimulation increases anger-related rumination. Psychol Sci. 2013 Apr;24(4):475–81.

    Article  PubMed  Google Scholar 

  63. Vanderhasselt M-A, De Raedt R, Namur V, Lotufo PA, Bensenor IM, Boggio PS, et al. Transcranial electric stimulation and neurocognitive training in clinically depressed patients: a pilot study of the effects on rumination. Prog Neuro-Psychopharmacol Biol Psychiatry. 2015 Mar;57:93–9. https://doi.org/10.1016/j.pnpbp.2014.09.015.

    Article  Google Scholar 

  64. Schmidt K, Cowen PJ, Harmer CJ, Tzortzis G, Errington S, Burnet PWJ. Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers. Psychopharmacology. 2015;232(10):1793–801. https://doi.org/10.1007/s00213-014-3810-0.

    Article  CAS  PubMed  Google Scholar 

  65. Nitsche MA, Koschack J, Pohlers H, Hullemann S, Paulus W, Happe S. Effects of frontal transcranial direct current stimulation on emotional state and processing in healthy humans. Front psychiatry [Internet]. 2012;3:58. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3377009&tool=pmcentrez&rendertype=abstract

    CAS  Google Scholar 

  66. Brunoni AR, Zanao TA, Vanderhasselt M-A, Valiengo L, de Oliveira JF, Boggio PS, et al. Enhancement of affective processing induced by bifrontal transcranial direct current stimulation in patients with major depression. Neuromodulation [Internet]. 2014;17(2):138–42. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23710817.

    Article  Google Scholar 

  67. Balzarotti S, Colombo B. Effects of unilateral transcranial direct current stimulation of left prefrontal cortex on processing and memory of emotional visual stimuli. PLoS One. 2016 Jul;11(7):e0159555. https://doi.org/10.1371/journal.pone.0159555.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Ironside M, O’Shea J, Cowen PJ, Harmer CJ. Frontal cortex stimulation reduces vigilance to threat: implications for the treatment of depression and anxiety. Biol Psychiatry [Internet] Elsevier. 2016;79(10):823–30. https://doi.org/10.1016/j.biopsych.2015.06.012.

    Article  Google Scholar 

  69. Clarke PJF, Browning M, Hammond G, Notebaert L, MacLeod C. The causal role of the dorsolateral prefrontal cortex in the modification of attentional bias: evidence from transcranial direct current stimulation. Biol Psychiatry [Internet] Elsevier. 2014;76(12):946–52. https://doi.org/10.1016/j.biopsych.2014.03.003.

    Article  Google Scholar 

  70. Heeren A, Baeken C, Vanderhasselt M-A, Philippot P, de Raedt R. Impact of anodal and cathodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex during attention bias modification: an eye-tracking study. PLoS One [Internet] Public Libr Sci. 2015;10(4):e0124182. https://doi.org/10.1371/journal.pone.0124182.

    Article  Google Scholar 

  71. Chen NTM, Basanovic J, Notebaert L, MacLeod C, Clarke PJF. Attentional bias mediates the effect of neurostimulation on emotional vulnerability. J Psychiatr Res. 2017;93:12–9. https://doi.org/10.1016/j.jpsychires.2017.05.008.

    Article  CAS  PubMed  Google Scholar 

  72. Sanchez A, Vanderhasselt M-A, Baeken C, De Raedt R. Effects of tDCS over the right DLPFC on attentional disengagement from positive and negative faces: an eye-tracking study. Cogn Affect Behav Neurosci. 2016;16(6):1027–38. https://doi.org/10.3758/s13415-016-0450-3.

    Article  PubMed  Google Scholar 

  73. Feeser M, Prehn K, Kazzer P, Mungee A, Bajbouj M. Transcranial direct current stimulation enhances cognitive control during emotion regulation. Brain Stimul. United States. 2014;7(1):105–12. https://doi.org/10.1016/j.brs.2013.08.006.

    Article  Google Scholar 

  74. Aboulafia-Brakha T, Manuel AL, Ptak R. Prefrontal transcranial direct current stimulation facilitates affective flexibility. Neuropsychologia. 2016 Jun;86:13–8. https://doi.org/10.1016/j.neuropsychologia.2016.03.030.

    Article  PubMed  Google Scholar 

  75. Nord CL, Forster S, Halahakoon DC, Penton-Voak IS, Munafo MR, Roiser JP. Prefrontal cortex stimulation does not affect emotional bias, but may slow emotion identification. Soc Cogn Affect Neurosci. 2017 May;12(5):839–47. https://doi.org/10.1093/scan/nsx007.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Martin DM, Yeung K, Loo CK. Pre-treatment letter fluency performance predicts antidepressant response to transcranial direct current stimulation. J Affect Disord. 2016;203:130–5. https://doi.org/10.1016/j.jad.2016.05.072.

    Article  PubMed  Google Scholar 

  77. Brunoni AR, Tortella G, Bensenor IM, Lotufo PA, Carvalho AF, Fregni F. Cognitive effects of transcranial direct current stimulation in depression: results from the SELECT-TDCS trial and insights for further clinical trials. J Affect Disord. 2016;202:46–52. https://doi.org/10.1016/j.jad.2016.03.066.

    Article  PubMed  Google Scholar 

  78. Pripfl J, Neumann R, Koehler U, Lamm C. Effects of transcranial direct current stimulation on risky decision making are mediated by ‘hot’ and ‘cold’ decisions, personality, and hemisphere. Eur J Neurosci. 2013 Dec;38(12):3778–85. https://doi.org/10.1111/ejn.12375.

    Article  PubMed  Google Scholar 

  79. Riva P, Lauro LJR, Vergallito A, DeWall CN, Bushman BJ. Electrified emotions: modulatory effects of transcranial direct stimulation on negative emotional reactions to social exclusion. Soc Neurosci. 2015;10(1):46–54. https://doi.org/10.1080/17470919.2014.946621.

    Article  PubMed  Google Scholar 

  80. Salehinejad MA, Nejati V, Derakhshan M. Neural correlates of trait resiliency: evidence from electrical stimulation of the dorsolateral prefrontal cortex (dLPFC) and orbitofrontal cortex (OFC). Pers Individ Dif. 2017 Feb;106:209–16. https://doi.org/10.1016/j.paid.2016.11.005.

    Article  Google Scholar 

  81. Brunoni AR, Vanderhasselt MA, Boggio PS, Fregni F, Dantas EM, Mill JG, et al. Polarity- and valence-dependent effects of prefrontal transcranial direct current stimulation on heart rate variability and salivary cortisol. Psychoneuroendocrinology. 2013;38(1):58–66. https://doi.org/10.1016/j.psyneuen.2012.04.020.

    Article  CAS  PubMed  Google Scholar 

  82. Woersching J, Padberg F, Ertl-Wagner B, Kumpf U, Kirsch B, Keeser D. Imaging transcranial direct current stimulation (tDCS) of the prefrontal cortex-correlation or causality in stimulation-mediated effects? Neurosci Biobehav Rev. 2016;69:333–56. https://doi.org/10.1016/j.neubiorev.2016.08.001.

    Article  Google Scholar 

  83. Keeser D, Meindl T, Bor J, Palm U, Pogarell O, Mulert C, et al. Prefrontal transcranial direct current stimulation changes connectivity of resting-state networks during fMRI. J Neurosci [Internet]. 2011;31(43):15284–93. Available from: http://www.jneurosci.org/content/31/43/15284.abstract. https://doi.org/10.1523/JNEUROSCI.0542-11.2011.

    Article  CAS  Google Scholar 

  84. Peña-Gómez C, Sala-Lonch R, Junqué C, Clemente IC, Vidal D, Bargalló N, et al. Modulation of large-scale brain networks by transcranial direct current stimulation evidenced by resting-state functional MRI. Brain Stimul. 2012;5(3):252–63. https://doi.org/10.1016/j.brs.2011.08.006.

    Article  PubMed  Google Scholar 

  85. Park C-H, Chang WH, Park J-Y, Shin Y-I, Kim ST, Kim Y-H. Transcranial direct current stimulation increases resting state interhemispheric connectivity. Neurosci Lett [Internet] Elsevier Ireland Ltd. 2013;539:7–10. Available from: http://www.sciencedirect.com/science/article/pii/S0304394013001031

    CAS  Google Scholar 

  86. Fox MD, Buckner RL, Liu H, Chakravarty MM, Lozano AM, Pascual-Leone A. Resting-state networks link invasive and noninvasive brain stimulation across diverse psychiatric and neurological diseases. Proc Natl Acad Sci. 2014 Oct;111(41):E4367–75. https://doi.org/10.1073/pnas.1405003111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Weber MJ, Messing SB, Rao H, Detre JA, Thompson-Schill SL. Prefrontal transcranial direct current stimulation alters activation and connectivity in cortical and subcortical reward systems: a tDCS-fMRI study. Hum Brain Mapp [Internet]. 2014 Aug 22;35(8):3673–86. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4107089/. https://doi.org/10.1002/hbm.22429.

  88. Holland R, Leff AP, Josephs O, Galea JM, Desikan M, Price CJ, et al. Speech facilitation by left inferior frontal cortex stimulation. Curr Biol [Internet]. Elsevier Ltd. 2011;21(16):1403–7. https://doi.org/10.1016/j.cub.2011.07.021.

    CAS  Google Scholar 

  89. Hone-Blanchet A, Edden RA, Fecteau S. Online effects of transcranial direct current stimulation in real time on human prefrontal and striatal metabolites. Biol Psychiatry [Internet]. 2016;80(6):432–8. Available from: http://www.sciencedirect.com/science/article/pii/S0006322315009610. https://doi.org/10.1016/j.biopsych.2015.11.008.

    Article  Google Scholar 

  90. Powell TY, Boonstra TW, Martin DM, Loo CK, Breakspear M. Modulation of cortical activity by transcranial direct current stimulation in patients with affective disorder. PLoS One. 2014 Jun;9(6):e98503. https://doi.org/10.1371/journal.pone.0098503.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Faehling F, Plewnia C. Controlling the emotional bias: performance, late positive potentials, and the effect of anodal transcranial direct current stimulation (tDCS). Front Cell Neurosci. 2016 Jun;10 https://doi.org/10.3389/fncel.2016.00159.

  92. Goegler N, Willacker L, Funk J, Strube W, Langgartner S, Napirkowski N, et al. Single-session transcranial direct current stimulation induces enduring enhancement of visual processing speed in patients with major depression. Eur Arch Psychiatry Clin Neurosci. 2017 Oct;267(7):671–86. https://doi.org/10.1007/s00406-016-0761-y.

    Article  Google Scholar 

  93. Pizzagalli DA. Depression, stress, and anhedonia: toward a synthesis and integrated model. Annu Rev Clin Psychol United States. 2014;10(1):393–423. https://doi.org/10.1146/annurev-clinpsy-050212-185606.

    Article  Google Scholar 

  94. Smittenaar P, FitzGerald THB, Romei V, Wright ND, Dolan RJ. Disruption of dorsolateral prefrontal cortex decreases model-based in favor of model-free control in humans. Neuron [Internet]. 2013;80(4):914–9. Available from: http://www.sciencedirect.com/science/article/pii/S0896627313007204. https://doi.org/10.1016/j.neuron.2013.08.009.

    Article  CAS  Google Scholar 

  95. Smittenaar P, Prichard G, FitzGerald THB, Diedrichsen J, Dolan RJ. Transcranial direct current stimulation of right dorsolateral prefrontal cortex does not affect model-based or model-free reinforcement learning in humans. PLoS One. 2014 Jan;9(1):e86850. https://doi.org/10.1371/journal.pone.0086850.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Brunoni AR, Zanao TA, Ferrucci R, Priori A, Valiengo L, de Oliveira JF, et al. Bifrontal tDCS prevents implicit learning acquisition in antidepressant-free patients with major depressive disorder. Prog Neuro-Psychopharmacol Biol Psychiatry. 2013 Jun;43:146–50. https://doi.org/10.1016/j.pnpbp.2012.12.019.

    Article  Google Scholar 

  97. Kronberg G, Bridi M, Abel T, Bikson M, Parra LC. Direct current stimulation modulates LTP and LTD: activity dependence and dendritic effects. BRAIN Stimul. 2017;10(1):51–8.

    Article  PubMed  Google Scholar 

  98. Kuo H-I, Paulus W, Batsikadze G, Jamil A, Kuo M-F, Nitsche MA. Acute and chronic effects of noradrenergic enhancement on transcranial direct current stimulation-induced neuroplasticity in humans. J Physiol. 2017 Feb;595(4):1305–14. https://doi.org/10.1113/JP273137.

    Article  CAS  PubMed  Google Scholar 

  99. Brunoni AR, Moffa AH, Sampaio-Junior B, Galvez V, Loo CK. Treatment-emergent mania/hypomania during antidepressant treatment with transcranial direct current stimulation (tDCS): a systematic review and meta-analysis. BRAIN Stimul. 2017;10(2):260–2. https://doi.org/10.1016/j.brs.2016.11.005.

    Article  PubMed  Google Scholar 

  100. Peet M. Induction of mania with selective serotonin re-uptake inhibitors and tricyclic antidepressants. Br J Psychiatry RCP. 1994;164(4):549–50. https://doi.org/10.1192/bjp.164.4.549.

    Article  CAS  Google Scholar 

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  1. Center for Depression, Anxiety and Stress Research, McLean Hospital, DeMarneffe Building, McLean Hospital, 115 Mill St, Belmont, MA, 02478, USA

    Maria Ironside & Sarah Perlo

  2. Harvard Medical School, Boston, MA, USA

    Maria Ironside

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  1. Maria Ironside
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Ironside, M., Perlo, S. Transcranial Direct Current Stimulation for the Treatment of Depression: a Review of the Candidate Mechanisms of Action. Curr Behav Neurosci Rep 5, 26–35 (2018). https://doi.org/10.1007/s40473-018-0138-9

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