Advertisement

Experimental Brain Research

, Volume 166, Issue 1, pp 23–30 | Cite as

Anodal transcranial direct current stimulation of prefrontal cortex enhances working memory

  • Felipe Fregni
  • Paulo S. Boggio
  • Michael Nitsche
  • Felix Bermpohl
  • Andrea Antal
  • Eva Feredoes
  • Marco A. Marcolin
  • Sergio P. Rigonatti
  • Maria T.A. Silva
  • Walter Paulus
  • Alvaro Pascual-Leone
Research Article

Abstract

Previous studies have claimed that weak transcranial direct current stimulation (tDCS) induces persisting excitability changes in the human motor cortex that can be more pronounced than cortical modulation induced by transcranial magnetic stimulation, but there are no studies that have evaluated the effects of tDCS on working memory. Our aim was to determine whether anodal transcranial direct current stimulation, which enhances brain cortical excitability and activity, would modify performance in a sequential-letter working memory task when administered to the dorsolateral prefrontal cortex (DLPFC). Fifteen subjects underwent a three-back working memory task based on letters. This task was performed during sham and anodal stimulation applied over the left DLPFC. Moreover seven of these subjects performed the same task, but with inverse polarity (cathodal stimulation of the left DLPFC) and anodal stimulation of the primary motor cortex (M1). Our results indicate that only anodal stimulation of the left prefrontal cortex, but not cathodal stimulation of left DLPFC or anodal stimulation of M1, increases the accuracy of the task performance when compared to sham stimulation of the same area. This accuracy enhancement during active stimulation cannot be accounted for by slowed responses, as response times were not changed by stimulation. Our results indicate that left prefrontal anodal stimulation leads to an enhancement of working memory performance. Furthermore, this effect depends on the stimulation polarity and is specific to the site of stimulation. This result may be helpful to develop future interventions aiming at clinical benefits.

Keywords

Electrical stimulation Prefrontal cortex Transcranial magnetic stimulation Working memory 

Notes

Acknowledgements

This work was supported by a grant within the Harvard Medical School Scholars in Clinical Science Program (NIH K30 HL04095-03) to F.F.; a grant within the Postdoc-Programme of the German Academic Exchange Service (DAAD, D/02/46858) to F.B.; and by K24 RR018875 to A.P.-L. The authors would like to thank Barbara Bonetti for the invaluable administrative support and to Adriana L. Vieira, Elizabeth M. Saade, Carolina R.B. Souza and Patricia Otachi for the help on data acquisition.

References

  1. Antal A, Nitsche MA, Paulus W (2001) External modulation of visual perception in humans. Neuroreport 12:3553–3555CrossRefPubMedGoogle Scholar
  2. Antal A, Kincses TZ, Nitsche MA, Bartfai O, Paulus W (2004a) Excitability changes induced in the human primary visual cortex by transcranial direct current stimulation: direct electrophysiological evidence. Invest Ophthalmol Vis Sci 45:702–707CrossRefPubMedGoogle Scholar
  3. Antal A, Nitsche MA, Kruse W, Kincses TZ, Hoffmann KP, Paulus W (2004b) Direct current stimulation over V5 enhances visuomotor coordination by improving motion perception in humans. J Cogn Neurosci 16:521–527CrossRefPubMedGoogle Scholar
  4. Baudewig J, Nitsche MA, Paulus W, Frahm J (2001) Regional modulation of BOLD MRI responses to human sensorimotor activation by transcranial direct current stimulation. Magn Reson Med 45:196–201CrossRefPubMedGoogle Scholar
  5. Bindman LJ, Lippold OC, Redfearn JW (1964) The action of brief polarizing currents on the cerebral cortex of the rat (1) during current flow and (2) in the production of long-lasting after-effects. J Physiol 172:369–382PubMedGoogle Scholar
  6. Boggio PS, Fregni F, Bermpohl F, Mansur CG, Rosa M, Rumi DO, Barbosa E, Odebrecht-Rosa M, Marcolin MA, Silva MTA (2005) The effect of repetitive TMS and fluoxetine on cognitive function in patients with Parkinson’s disease and concurrent depression. Mov Disord (in press). DOI 10.1002/mds.20508Google Scholar
  7. Creutzfeldt OD, Fromm GH, Kapp H (1962) Influence of transcortical d-c currents on cortical neuronal activity. Exp Neurol 5:436–452CrossRefPubMedGoogle Scholar
  8. D’Esposito M, Aguirre GK, Zarahn E, Ballard D, Shin RK, Lease J (1998) Functional MRI studies of spatial and nonspatial working memory. Brain Res Cogn Brain Res 7:1–13CrossRefPubMedGoogle Scholar
  9. Gerloff C, Corwell B, Chen R, Hallett M, Cohen LG (1997) Stimulation over the human supplementary motor area interferes with the organization of future elements in complex motor sequences. Brain 120(Pt 9):1587–1602CrossRefPubMedGoogle Scholar
  10. Grafman J, Pascual-Leone A, Alway D, Nichelli P, Gomez-Tortosa E, Hallett M (1994) Induction of a recall deficit by rapid-rate transcranial magnetic stimulation. Neuroreport 5:1157–1160PubMedGoogle Scholar
  11. Herwig U, Satrapi P, Schonfeldt-Lecuona C (2003) Using the international 10–20 EEG system for positioning of transcranial magnetic stimulation. Brain Topogr 16:95–99CrossRefPubMedGoogle Scholar
  12. Jahanshahi M, Profice P, Brown RG, Ridding MC, Dirnberger G, Rothwell JC (1998) The effects of transcranial magnetic stimulation over the dorsolateral prefrontal cortex on suppression of habitual counting during random number generation. Brain 121(Pt 8):1533–1544CrossRefPubMedGoogle Scholar
  13. Kincses TZ, Antal A, Nitsche MA, Bartfai O, Paulus W (2004) Facilitation of probabilistic classification learning by transcranial direct current stimulation of the prefrontal cortex in the human. Neuropsychologia 42:113–117CrossRefPubMedGoogle Scholar
  14. Martis B, Alam D, Dowd SM, Hill SK, Sharma RP, Rosen C, Pliskin N, Martin E, Carson V, Janicak PG (2003) Neurocognitive effects of repetitive transcranial magnetic stimulation in severe major depression. Clin Neurophysiol 114:1125–1132CrossRefPubMedGoogle Scholar
  15. Moser DJ, Jorge RE, Manes F, Paradiso S, Benjamin ML, Robinson RG (2002) Improved executive functioning following repetitive transcranial magnetic stimulation. Neurology 58:1288–1290PubMedGoogle Scholar
  16. Mottaghy FM, Krause BJ, Kemna LJ, Topper R, Tellmann L, Beu M, Pascual-Leone A, Muller-Gartner HW (2000) Modulation of the neuronal circuitry subserving working memory in healthy human subjects by repetitive transcranial magnetic stimulation. Neurosci Lett 280:167–170CrossRefPubMedGoogle Scholar
  17. Mull BR, Seyal M (2001) Transcranial magnetic stimulation of left prefrontal cortex impairs working memory. Clin Neurophysiol 112:1672–1675CrossRefPubMedGoogle Scholar
  18. Nitsche MA, Paulus W (2000) Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol 527(Pt 3):633–639CrossRefPubMedGoogle Scholar
  19. Nitsche MA, Paulus W (2001) Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans. Neurology 57:1899–1901PubMedGoogle Scholar
  20. Nitsche MA, Liebetanz D, Antal A, Lang N, Tergau F, Paulus W (2003a) Modulation of cortical excitability by weak direct current stimulation—technical, safety and functional aspects. Suppl Clin Neurophysiol 56:255–276PubMedGoogle Scholar
  21. Nitsche MA, Liebetanz D, Lang N, Antal A, Tergau F, Paulus W (2003b) Safety criteria for transcranial direct current stimulation (tDCS) in humans. Clin Neurophysiol 114:2220–2222 CrossRefPubMedGoogle Scholar
  22. Nitsche MA, Schauenburg A, Lang N, Liebetanz D, Exner C, Paulus W, Tergau F (2003c) Facilitation of implicit motor learning by weak transcranial direct current stimulation of the primary motor cortex in the human. J Cogn Neurosci 15:619–626CrossRefPubMedGoogle Scholar
  23. Nitsche MA, Liebetanz D, Schlitterlau A, Henschke U, Fricke K, Frommann K, Lang N, Henning S, Paulus W, Tergau F (2004) GABAergic modulation of DC stimulation-induced motor cortex excitability shifts in humans. Eur J Neurosci 19:2720–2726CrossRefPubMedGoogle Scholar
  24. Padberg F, Zwanzger P, Thoma H, Kathmann N, Haag C, Greenberg BD, Hampel H, Moller HJ (1999) Repetitive transcranial magnetic stimulation (rTMS) in pharmacotherapy-refractory major depression: comparative study of fast, slow and sham rTMS. Psychiatry Res 88:163–171CrossRefPubMedGoogle Scholar
  25. Pascual-Leone A, Hallett M (1994) Induction of errors in a delayed response task by repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex. Neuroreport 5:2517–2520PubMedGoogle Scholar
  26. Pascual-Leone A, Bartres-Faz D, Keenan J (1999) Transcranial magnetic stimulation: studying the brain–behaviour relationship by induction of “virtual lesions”. Philos Trans R Soc Lond B Biol Sci 354:1229–1238CrossRefPubMedGoogle Scholar
  27. Purpura DP, McMurtry JG (1965) Intracellular activities and evoked potential changes during polarization of motor cortex. J Neurophysiol 28:166–185PubMedGoogle Scholar
  28. Rosenkranz K, Nitsche MA, Tergau F, Paulus W (2000) Diminution of training-induced transient motor cortex plasticity by weak transcranial direct current stimulation in the human. Neurosci Lett 296:61–63CrossRefPubMedGoogle Scholar
  29. Rossi S, Cappa SF, Babiloni C, Pasqualetti P, Miniussi C, Carducci F, Babiloni F, Rossini PM (2001) Prefrontal [correction of Prefontal] cortex in long-term memory: an “interference” approach using magnetic stimulation. Nat Neurosci 4:948–952CrossRefPubMedGoogle Scholar
  30. Sauseng P, Klimesch W, Doppelmayr M, Hanslmayr S, Schabus M, Gruber WR (2004) Theta coupling in the human electroencephalogram during a working memory task. Neurosci Lett 354:123–126CrossRefPubMedGoogle Scholar
  31. Siebner HR, Lang N, Rizzo V, Nitsche MA, Paulus W, Lemon RN, Rothwell JC (2004) Preconditioning of low-frequency repetitive transcranial magnetic stimulation with transcranial direct current stimulation: evidence for homeostatic plasticity in the human motor cortex. J Neurosci 24:3379–3385CrossRefPubMedGoogle Scholar
  32. Smith EE, Jonides J (1999) Storage and executive processes in the frontal lobes. Science 283:1657–1661CrossRefPubMedGoogle Scholar
  33. Uy J, Ridding MC (2003) Increased cortical excitability induced by transcranial DC and peripheral nerve stimulation. J Neurosci Methods 127(24):193–197CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Felipe Fregni
    • 1
  • Paulo S. Boggio
    • 2
  • Michael Nitsche
    • 3
  • Felix Bermpohl
    • 1
  • Andrea Antal
    • 3
  • Eva Feredoes
    • 3
  • Marco A. Marcolin
    • 4
  • Sergio P. Rigonatti
    • 4
  • Maria T.A. Silva
    • 2
  • Walter Paulus
    • 3
  • Alvaro Pascual-Leone
    • 1
  1. 1.Harvard Center for Non-invasive Brain Stimulation, Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonUSA
  2. 2.Department of Experimental Psychology, Institute of PsychologyUniversity of Sao PauloSao PauloBrazil
  3. 3.Department of Clinical NeurophysiologyGeorg-August-UniversityGoettingenGermany
  4. 4.Department of PsychiatryUniversity of Sao PauloSao PauloBrazil

Personalised recommendations