Experimental Brain Research

, Volume 183, Issue 3, pp 361–369 | Cite as

Classical conditioned learning using transcranial magnetic stimulation

  • B. LuberEmail author
  • P. Balsam
  • T. Nguyen
  • M. Gross
  • S. H. Lisanby
Research Article


This study examined whether brain responses to transcranial magnetic stimulation (TMS) would be amenable to classical conditioning. Motor cortex in human participants was stimulated with TMS pulses, which elicited a peripheral motor response in the form of a motor evoked potential (MEP). The TMS pulses were paired with audio-visual cues that served as conditioned stimuli. Over the course of training, MEPs following the conditioned stimuli decreased in amplitude. Two experiments demonstrated that the attenuated response only occurred when the TMS was preceded by the conditioned stimulus. Unsignaled TMS and TMS preceded by a cue that was not previously paired did not attenuate the response. The experiments demonstrate that the modulation of the motor response depended on the prior pairings of the conditioned stimuli and TMS and that the effects were stimulus specific. Thus we demonstrate here, for the first time, that TMS can serve as the unconditioned stimulus in Pavlovian conditioning.


Classical conditioning TMS Motor cortex Conditioned compensatory response 



This research was supported by a grant from the Defense Advanced Research Projects Agency (DARPA) and by grant MH068073 to PB. Approved for public release, distribution unlimited. Dr Lisanby has received support from Magstim Company, Neuronetics and Cyberonics.


  1. Bahrick LE, Lickliter R, Flom R (2004) Intersensory redundancy guides the development of selective attention, perception, and cognition in infancy. Curr Dir Psychol Sci 13:99–102CrossRefGoogle Scholar
  2. Boroojerdi B, Phipps M, Kopylev L, Wharton CM, Cohen LG, Grafman J (2001) Enhancing analogic reasoning with rTMS over the left prefrontal cortex. Neurology 56:526–528PubMedGoogle Scholar
  3. Chen R, Classen J, Gerloff C, Celnik P, Wassermann E, Hallett M, Cohen L (1997) Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation, Neurology 48:1398–1403PubMedGoogle Scholar
  4. Di Lazzaro V, Oliviero A, Pilato F, Saturno E, Dileone M, Mazzone P, Insola A, Tonali PA, Rothwell JC (2004) The physiological basis of transcranial motor cortex stimulation in conscious humans. Clin Neurophysiol 115:255–266PubMedCrossRefGoogle Scholar
  5. Doty RW (1969) Electrical stimulation of the brain in behavioral context. Annu Rev Psychol 20:289–320PubMedCrossRefGoogle Scholar
  6. Doty RW, Giurgea C (1961) Conditioned reflexes established by coupling electrical excitation of two cortical areas. In: Delafresnaye JF (ed) Brain mechanisms and learning. Blackwell Scientific Publications, OxfordGoogle Scholar
  7. Epstein CM, Schwartzberg DG, Davey KR, Sudderth DB (1990) Localizing the site of magnetic brain stimulation in humans. Neurology 40:666–670PubMedGoogle Scholar
  8. Evers S, Bockermann I, Nyhuis PW (2001) The impact of transcranial magnetic stimulation on cognitive processing: an event-related potential study. NeuroReport 12:2915–2918PubMedCrossRefGoogle Scholar
  9. Fanselow MS, Poulos AM (2005) The neuroscience of mammalian associative learning. Annu Rev Psychol 56:207–234PubMedCrossRefGoogle Scholar
  10. Fisher RJ, Sharott A, Kuhn AA, Brown P (2004) Effects of combined cortical and acoustic stimuli on muscle activity. Exp Brain Res 157:1–9PubMedCrossRefGoogle Scholar
  11. Furubayashi T, Ugawa Y, Terao Y, Hanajima R, Sakai K, Machii K, Mochizuki H, Shiio Y, Uesugi H, Enomoto H, Kanazawa I (2000) The human hand motor area is transiently suppressed by an unexpected auditory stimulus. Clin Neurophysiol 111:178–183PubMedCrossRefGoogle Scholar
  12. Gilio F, Rizzo V, Siebner HR, Rothwell JC (2003) Effects on the right motor hand area excitability produced by low-frequency rTMS over human contralateral homologous cortex. J Physiol 509:607–618Google Scholar
  13. Grosbras M-H, Paus T (2003) Transcranial magnetic stimulation of the human frontal eye field facilitates visual awareness. Eur J Neurosci 18:3121–3126PubMedCrossRefGoogle Scholar
  14. Gutiérrez-Cebollada J, de la Torre R, Ortuno J, Garces JM, Cami J (1994) Psychotropic drug consumption and other factors associated with heroin overdose. Drug Alcohol Depend 35:169–174PubMedCrossRefGoogle Scholar
  15. Hayward G, Goodwin GM, Harmer CJ (2004) The role of the anterior cingulate cortex in the counting Stroop task. Exp Brain Res 154:355–358PubMedCrossRefGoogle Scholar
  16. Heide G, Witte OW, Ziemann U (2006) Physiology of modulation of motor cortex excitability by low frequency suprathreshold repetitive transcranial magnetic stimulation. Exp Brain Res 171:26–34PubMedCrossRefGoogle Scholar
  17. Kandel GL, Benevento LA (1973) Classically conditioned limb reflexes reinforced by motor cortex stimulation. Physiol Behav 11(4):481–488PubMedCrossRefGoogle Scholar
  18. Klimesch W, Sauseng P, Gerloff C (2003) Enhancing cognitive performance with repetitive transcranial magnetic stimulation at human individual alpha frequency. Eur J Neurosci 17:1129–1133PubMedCrossRefGoogle Scholar
  19. Kobayashi M, Pascual-Leone A (2003) Transcranial magnetic stimulation in neurology. Lancet Neurology 2:145–156PubMedCrossRefGoogle Scholar
  20. Kohler S, Paus T, Buckner RL, Milner B (2004) Effects of left inferior prefrontal stimulation on episodic memory formation: a two-stage fMRI-rTMS study. J Cogn Neurosci 16:178–188PubMedCrossRefGoogle Scholar
  21. Lisanby SH, Luber B, Sackeim HA (2000) Transcranial magnetic stimulation: applications in basic neuroscience and neuropsychopharmacology. Int J Neuropsychopharmacol 2:259–273CrossRefGoogle Scholar
  22. Loucks RB (1935) The experimental delimitation of neural structures essential for learning. The attempt to condition striped muscle responses with faradization of the sigmoid gyri. J Psychol 1:5–44Google Scholar
  23. Luber B, Kinnunen LH, Rakitin BC, Ellsasser R, Stern Y, Lisanby SH (2007) Facilitation of performance in a working memory task with rTMS stimulation of the precuneus: frequency and time-dependent effects. Brain Res 1128:120–129PubMedCrossRefGoogle Scholar
  24. Marchand AR, Kamper E (2000) Time course of cardiac conditioned responses in restrained rats as a function of the trace CS-US interval. J Exp Psychol Anim Behav Process 26:385–398PubMedCrossRefGoogle Scholar
  25. McKusker CG, Brown K (1990) Alcohol-predictive cues enhance tolerance to and precipitate “craving” for alcohol in social drinkers. J Stud Alcohol 51:494–499Google Scholar
  26. Muellbacher W, Ziemann U, Boroojerdi B, Cohen L, Hallett M (2001) Role of the human cortex in rapid motor learning. Exp Brain Res 136:431–438PubMedCrossRefGoogle Scholar
  27. Muellbacher W, Ziemann U, Boroojerdi B, Hallett M (2000) Effects of low-frequency transcranial magnetic stimulation on motor excitability and basic motor behavior. Clin Neurophysiol 111:1002–1007PubMedCrossRefGoogle Scholar
  28. Paz R, Boraud T, Natan C, Bergman H, Vaadia E (2003) Preparatory activity in motor cortex reflects learning of local visuomotor skills. Nature Neurosci 6:882–890PubMedCrossRefGoogle Scholar
  29. Plewnia C, Lotze M, Gerloff C (2003) Disinhibition of the contralateral motor cortex by low frequency rTMS. Neuroreport 14:609–612PubMedCrossRefGoogle Scholar
  30. Rescorla RA, Wagner AR (1972) A theory of Pavlovian conditioning: variations in the effectiveness of reinforcement and nonreinforcement. In: Black A, Prokasy WF (eds) Classical conditioning II: current research and theory. Appleton-Century-Crofts, New York, pp 64–99Google Scholar
  31. Rossini PM, Barker AT, Berardelli A, Caramia MD, Caruso G, Cracco RQ, Dimitrijevic MR, Hallett M, Katayama Y, Lucking CH, Maertens de Noordhout AL, Marsden CD, Murray NMF, Rothwell JC, Swash M, Tomberg C (1994) Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application. Report of an IFCN committee. Electroencephalogr Clin Neurophysiol 91:79–92PubMedCrossRefGoogle Scholar
  32. Siebner HR, Auer C, Conrad B (1999) Abnormal increase in the corticomotor output to the affected hand during repetitive transcranial magnetic stimulation of the primary motor cortex in patients with writer’s cramp. Neurosci Lett 262:133–136PubMedCrossRefGoogle Scholar
  33. Siegel S (1975) Evidence from rats that morphine tolerance is a learned response. J Comp Physiol Psychol 89:498–506PubMedCrossRefGoogle Scholar
  34. Siegel S (2005) Two views of the addiction elephant: comment on McSweeney, Murphy, and Kowal (2005). Exp Clin Psychopharmacol 13:190–193PubMedCrossRefGoogle Scholar
  35. Siegel S, Ramos B (2002) Applying laboratory research: drug anticipation and the treatment of drug addiction. Exp Clin Psychopharmacol 10:162–183PubMedCrossRefGoogle Scholar
  36. Sparing R, Mottaghy FM, Hungs M, Brugmann M, Foltys H, Huber W, Topper R (2001) Repetitive transcranial magnetic stimulation effects on language function depend on the stimulation parameters. J Clin Neurophysiol 18:326–330PubMedCrossRefGoogle Scholar
  37. Thompson RF (2005) In search of memory traces. Annu Rev Psychol 56:1–24PubMedCrossRefGoogle Scholar
  38. Topper R, Mottaghy FM, Brugmann M, Noth J, Huber W (1998) Facilitation of picture naming by focal transcranial magnetic stimulation of Wernicke’s area. Exp Brain Res 121:371–378PubMedCrossRefGoogle Scholar
  39. Wagner AR, Thomas E, Norton T (1967) Conditioning with electrical stimulation of motor cortex: evidence of a possible source of motivation. J Comp Physiol Psychol 64:191–199PubMedCrossRefGoogle Scholar
  40. Wise SP, Moody SL, Blomstrom KJ, Mitz AR (1998) Changes in motor cortical activity during visuomotor adaptation. Exp Brain Res 121:285–299PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • B. Luber
    • 1
    Email author
  • P. Balsam
    • 1
    • 2
  • T. Nguyen
    • 1
  • M. Gross
    • 1
  • S. H. Lisanby
    • 1
  1. 1.Brain Stimulation and Therapeutic Modulation Division, New York State Psychiatric Institute and Department of PsychiatryColumbia University College of Physicians and SurgeonsNew YorkUSA
  2. 2.Department of PsychologyBarnard CollegeNew YorkUSA

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