Experimental Brain Research

, Volume 164, Issue 3, pp 323–333

Orientation-specific fast rTMS maximizes corticospinal inhibition and facilitation

  • Tobias Tings
  • Nicolas Lang
  • Frithjof Tergau
  • Walter Paulus
  • Martin Sommer
Research Article


Specific stimulation of neuronal circuits may promote selective inhibition or facilitation of corticospinal tract excitability. Monophasic stimulation is more likely to achieve direction-specific neuronal excitation. In 10 healthy subjects, we compared four types of repetitive transcranial magnetic stimulation (rTMS), monophasic and biphasic stimuli with the initial current in the brain flowing antero-posteriorly (“posteriorly directed”) or postero-anteriorly (“anteriorly directed”). We applied rTMS over the primary motor cortex contralateral to the dominant hand, using 80 stimuli at 5 Hz frequency at an intensity yielding baseline motor evoked potential (MEP) amplitudes of 1 mV. Monophasic stimulation was always more efficient than biphasic. Facilitation was induced by intracerebral anteriorly directed current flow and inhibition by posteriorly oriented current flow, although only initially for approximately 30 pulses. The early inhibition was absent when studied during a tonic muscle contraction. Several mechanisms could account for these findings. They include a more efficient excitation of inhibiting circuits by posteriorly oriented pulses, and a back-propagating D-wave inhibiting early I-waves and thus inducing early inhibition of MEP amplitude. In any case biphasic rTMS results can be explained by a mixture of monophasic opposite stimulations. We propose the use of monophasic pulses for maximizing effects during rTMS.


Transcranial magnetic stimulation Motor cortex Inhibition Facilitation D-waves and I-waves 


  1. Amassian VE, Cracco RQ, Maccabee PJ (1989) Focal stimulation of human cerebral cortex with the magnetic coil: a comparison with electrical stimulation. Electroencephalogr Clin Neurophysiol 74:401–416CrossRefGoogle Scholar
  2. Arai N, Okabe S, Furubayashi T, Terao Y, Yuasa K, Ugawa Y (2005) Comparison between short train, monophasic and biphasic repetitive transcranial magnetic stimulation (rTMS) of the human motor cortex. Clin Neurophysiol 116:605–613 CrossRefPubMedGoogle Scholar
  3. Ashby P, Reynolds C, Wennberg R, Lozano AM, Rothwell J (1999) On the focal nature of inhibition and facilitation in the human motor cortex. Clin Neurophysiol 110:550–555CrossRefPubMedGoogle Scholar
  4. Bartlett JR, Doty RW, Lee BB, Negrao N, Overmann WH (1977) Deleterious effects of prolonged electrical stimulation of striate cortex in Macaques. Brain Behav Evol 14Google Scholar
  5. Berardelli A, Inghilleri M, Rothwell JC, Romeo S, Curra A, Gilio F, Modugno N, Manfredi M (1998) Facilitation of muscle evoked responses after repetitive cortical stimulation in man. Exp Brain Res 122:79–84CrossRefPubMedGoogle Scholar
  6. Chen R (2004) Interactions between inhibitory and excitatory circuits in the human motor cortex. Exp Brain Res 154:1–10CrossRefPubMedGoogle Scholar
  7. Chen R, Classen J, Gerloff C, Celnik P, Wassermann EM, Hallett M, Cohen LG (1997) Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation. Neurology 48:1398–1403PubMedGoogle Scholar
  8. Di Lazzaro V, Restuccia D, Oliviero A, Profice P, Ferrara L, Insola A, Mazzone P, Tonali P, Rothwell JC (1998) Effects of voluntary contraction on descending volleys evoked by transcranial stimulation in conscious humans. J Physiol 508:625–633CrossRefPubMedGoogle Scholar
  9. Di Lazzaro V, Oliviero A, Saturno E, Pilato F, Insola A, Mazzone P, Profice P, Tonali P, Rothwell JC (2001) The effect on corticospinal volleys of reversing the direction of current induced in the motor cortex by transcranial magnetic stimulation. Exp Brain Res 138:268–273CrossRefPubMedGoogle Scholar
  10. Di Lazzaro V, Oliviero A, Pilato F, Saturno E, Insola A, Mazzone P, Tonali PA, Rothwell JC (2002b) Descending volleys evoked by transcranial magnetic stimulation of the brain in conscious humans: effects of coil shape. Clin Neurophysiol 113:114–119CrossRefPubMedGoogle Scholar
  11. Di Lazzaro V, Oliviero A, Berardelli A, Mazzone P, Insola A, Pilato F, Saturno E, Dileone M, Tonali PA, Rothwell JC (2002a) Direct demonstration of the effects of repetitive transcranial magnetic stimulation on the excitability of the human motor cortex. Exp Brain Res 144:549–553CrossRefPubMedGoogle Scholar
  12. Di Lazzaro V, Oliviero A, Mazzone P, Pilato F, Saturno E, Dileone M, Tonali PA (2003) Generation of I-waves in the human: spinal recordings. Clin Neurophysiol 56(Suppl):S143–S152Google Scholar
  13. Di Lazzaro V, Oliviero A, Pilato F, Saturno E, Dileone M, Meglio M, Cioni B, Papacci F, Tonali PA, Rothwell JC (2004) Comparison of descending volleys evoked by transcranial and epidural motor cortex stimulation in a conscious patient with bulbar pain. Clin Neurophysiol 115:834–838CrossRefPubMedGoogle Scholar
  14. Girvin JP (1978) A review of basic aspects concerning chronic cerebral stimulation. In: Cooper IS (ed) Cerebellar stimulation in man. Raven Press, New York, pp 1–12Google Scholar
  15. Huang YZ, Edwards MJ, Rünis E, Bathia KP, Rothwell JC (2005) Theta burst stimulation of the human cortex. Neuron 45:201–206CrossRefPubMedGoogle Scholar
  16. Kammer T, Beck S, Thielscher A, Laubis-Herrmann U, Topka H (2001) Motor threshold in humans: a transcranial magnetic stimulation study comparing different pulse waveforms, current directions and stimulator types. Clin Neurophysiol 112:250–258CrossRefPubMedGoogle Scholar
  17. Kujirai T, Caramia MD, Rothwell JC, Day BL, Thompson PD, Ferbert A, Wroe S, Asselman P, Marsden CD (1993) Corticocortical inhibition in human motor cortex. J Physiol 471:501–519PubMedGoogle Scholar
  18. Lang N, Siebner HR, Ernst D, Nitsche MA, Paulus W, Lemon RN, Rothwell JC (2004) Preconditioning with transcranial DC stimulation sensitizes the motor cortex to rapid-rate TMS and controls the direction of after-effects. Biol Psychiatry 56:634–639CrossRefPubMedGoogle Scholar
  19. Maccabee PJ, Nagaranjan SS, Amassian VE, Durand DM, Szabo AZ, Ahad AB, Cracco RQ, Lai KS, Eberle LP (1998) Influence of pulse sequence, polarity and amplitude on magnetic stimulation of human and porcine peripheral nerve. J Physiol 513:571–585CrossRefPubMedGoogle Scholar
  20. 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 111:1002–1007CrossRefPubMedGoogle Scholar
  21. Niehaus L, Meyer BU, Weyh T (2000) Influence of pulse configuration and direction of coil current on excitatory effects of magnetic motor cortex and nerve stimulation. Clin Neurophysiol 111:75–80CrossRefPubMedGoogle Scholar
  22. Nitsche MA, Paulus W (2000) Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol 527:633–639CrossRefPubMedGoogle Scholar
  23. Orth M, Rothwell JC (2004) The cortical silent period: intrinsic variability and relation to the waveform of the transcranial magnetic stimulation pulse. Clin Neurophysiol 115:1076–1082CrossRefPubMedGoogle Scholar
  24. Pascual-Leone A, Valls-Sole J, Wassermann EM, Hallett M (1994) Responses to rapid-rate transcranial magnetic stimulation of the human motor cortex. Brain 117:847–858PubMedGoogle Scholar
  25. Patten HD, Amassian VE (1954) Single-unit and multiple-unit analysis of cortical stage of pyramidal tract activation. J Neurophysiol 17:345–363PubMedGoogle Scholar
  26. Peinemann A, Lehner C, Mentschel C, Munchau A, Conrad B, Siebner HR (2000) Subthreshold 5-Hz repetitive transcranial magnetic stimulation of the human primary motor cortex reduces intracortical paired-pulse inhibition. Neurosci Lett 15:21–24CrossRefGoogle Scholar
  27. Romeo S, Gilio F, Pedace F, Ozkaynak S, Inghilleri M, Manfredi M, Berardelli A (2000) Changes in the cortical silent period after repetitive magnetic stimulation of cortical motor areas. Exp Brain Res 135:504–510CrossRefPubMedGoogle Scholar
  28. Rothwell JC (1991) Physiological studies of electric and magnetic stimulation of the human brain. Electroencephalogr Clin Neurophysiol 43(Suppl):S29–S35Google Scholar
  29. Rothwell JC, Thompson PD, Day BL, Boyd S, Marsden CD (1991) Stimulation of the human motor cortex through the scalp. Exp Physiol 76:159–200PubMedGoogle Scholar
  30. Rothwell JC, Hallett M, Berardelli A, Eisen A, Rossini P, Paulus W (1999) Magnetic stimulation: motor evoked potentials. In: Deuschl G, Eisen A (eds) Recommendations for the practice of clinical neurophysiology: guidelines of the international federation of clinical neurophysiology. Elsevier Science BV, Amsterdam, pp 97–103Google Scholar
  31. Sakai K, Ugawa Y, Terao Y, Hanajima R, Furubayashi T, Kanazawa I (1997) Preferential activation of different I-waves by transcranial magnetic stimulation with a figure-of-eight-shaped coil. Exp Brain Res 113:24–32PubMedGoogle Scholar
  32. 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
  33. Sommer M, Paulus W (2003) Pulse configuration and rTMS efficacy: a review of clinical studies. Clin Neurophysiol 56(Suppl 1):S33–S41Google Scholar
  34. Sommer M, Tergau F, Wischer S, Paulus W (2001) Paired-pulse repetitive transcranial magnetic stimulation of the human motor cortex. Exp Brain Res 139:465–472CrossRefPubMedGoogle Scholar
  35. Sommer M, Lang N, Tergau F, Paulus W (2002) Neuronal tissue polarization induced by repetitive transcranial magnetic stimulation?. Neuroreport 13:809–811CrossRefPubMedGoogle Scholar
  36. Sommer M, Lang N, Tings T, Tergau F, Paulus W (2003) Bipolar versus monopolar transcranial magnetic stimulation. Proceedings of the 29th Göttingen neurobiology conference, 12–15 June 2003, Abstract 1123: http://www.neuro.uni-goettingen.de/pdf/proceedings2003.pdf
  37. Tings T, Lang N, Tergau F, Paulus W, Sommer M (2004) Reversal of high-frequency repetitive transcranial magnetic stimulation induced facilitation by inverse monophasic stimulation in humans. Mov Disord 19(Suppl 9):S41CrossRefGoogle Scholar
  38. Touge T, Gerschlager W, Brown P, Rothwell J (2001) Are the after-effects of low-frequency rTMS on motor cortex excitability due to changes in the efficacy of cortical synapses?. Clin Neurophysiol 112:2138–2145CrossRefPubMedGoogle Scholar
  39. Wassermann EM (1998) Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the international workshop on the safety of repetitive transcranial magnetic stimulation, 5–7 June 1996. Electroencephalogr Clin Neurophysiol 108:1–16CrossRefPubMedGoogle Scholar
  40. Wassermann EM, Lisanby SH (2001) Therapeutic application of repetitive transcranial magnetic stimulation: a review. Clin Neurophysiol 112:1367–1377CrossRefPubMedGoogle Scholar
  41. Wassermann EM, Wang B, Zeffiro TA, Sadato N, Pascual-Leone A, Toro C, Hallett M (1996) Locating the motor cortex on the MRI with transcranial magnetic stimulation and PET. Neuroimage 3:1–9CrossRefPubMedGoogle Scholar
  42. Wu T, Sommer M, Tergau F, Paulus W (2000) Lasting influence of repetitive transcranial magnetic stimulation on intracortical excitability in human subjects. Neurosci Lett 287:37–40CrossRefPubMedGoogle Scholar
  43. Ziemann U, Rothwell JC (2000) I-waves in motor cortex. J Clin Neurophysiol 17:397–405CrossRefPubMedGoogle Scholar
  44. Ziemann U, Rothwell JC, Ridding MC (1996) Interaction between intracortical inhibition and facilitation in human motor cortex. J Physiol 496:873–881PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Tobias Tings
    • 1
  • Nicolas Lang
    • 1
  • Frithjof Tergau
    • 1
  • Walter Paulus
    • 1
  • Martin Sommer
    • 1
  1. 1.Department of Clinical NeurophysiologyUniversity of GöttingenGöttingenGermany

Personalised recommendations