Skip to main content
SpringerLink
Log in

The effects of low- and high-frequency repetitive TMS on the input/output properties of the human corticospinal pathway

  • Research Article
  • Published:
Experimental Brain Research Aims and scope Submit manuscript

Abstract

The objective of this study was to characterize the effects of various parameters (notably the frequency and intensity) of repetitive transcranial magnetic stimulation (rTMS) applied over the primary motor (M1) and premotor (PMC) cortices on the excitability of the first dorsalis interosseus (FDI) corticospinal pathway. To this end, we applied a comprehensive input–output analysis after fitting the experimental results to a sigmoidal function. Twenty-six healthy subjects participated in the experiments. Repetitive TMS was applied either over M1 or PMC at 1 Hz (LF) for 30 min (1,800 pulses) or at 20 Hz (HF) for 20 min (1,600 pulses). In the HF condition, the TMS intensity was set to 90% (HF90) of the FDI’s resting motor threshold (RMT). In the LF condition, the TMS intensity was set to either 90% (LF90) or 115% (LF115) of the RMT. The FDI input/output (I/O) curve was measured on both sides of the body before rTMS (the Pre session) and then during two Post sessions. For each subject, the I/O curves (i.e., the integral of the FDI motor-evoked potential (MEP) vs. stimulus intensity) were fitted using a Boltzmann sigmoidal function. The graph’s maximum slope, S 50 and plateau value were then compared between Pre and Post sessions. LF115 over M1 increased the slope of the FDI I/O curve but did not change the S 50 and plateau value. This also suggested an increase in the RMT. HF90 led to a more complex effect, with an increase in the slope and a decrease in the S 50 and plateau value. We did not see a cross effect on the homologous FDI corticospinal pathway, and only PMC LF90 had an effect on ipsilateral corticospinal excitability. Our results suggest that rTMS may exert a more complex influence on cortical network excitability than is usually reported (i.e. simple inhibitory or facilitatory effects). Analysis of the fitted stimulus response curve indicates a dichotomous influence of both low- and high-frequency rTMS on M1 cortical excitability; this may reflect intermingled effects on excitatory and inhibitory cortical networks.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Bäumer T, Lange R, Liepert J, Weiller C, Siebner HR, Rothwell JC, Münchau A (2003) Repeated premotor rTMS leads to cumulative plastic changes of motor cortex excitability in humans. Neuroimage 20:550–560

    Article  PubMed  Google Scholar 

  • Baumer T, Bock F, Koch G, Lange R, Rothwell JC, Siebner HR, Munchau A (2006) Magnetic stimulation of human premotor or motor cortex produces interhemispheric facilitation through distinct pathways. J Physiol 572:857–868

    PubMed  Google Scholar 

  • Boroojerdi B, Battaglia F, Muellbacher W, Cohen LG (2001) Mechanisms influencing stimulus-response properties of the human corticospinal system. Clin Neurophysiol 112:931–937

    Article  PubMed  CAS  Google Scholar 

  • Boylan LS, Pullman SL, Lisanby SH, Spicknall KE, Sackeim HA (2001) Repetitive transcranial magnetic stimulation to SMA worsens complex movements in Parkinson’s disease. Clin Neurophysiol 112:259–264

    Article  PubMed  CAS  Google Scholar 

  • Capaday C (1997) Neurophysiological methods for studies of the motor system in freely moving human subjects. J Neurosci Methods 74:201–218

    Article  PubMed  CAS  Google Scholar 

  • Capaday C, Lavoie BA, Barbeau H, Schneider C, Bonnard M (1999) Studies on the corticospinal control of human walking I: responses to focal transcranial magnetic stimulation of the motor cortex. J Neurophysiol 81:129–139

    PubMed  CAS  Google Scholar 

  • 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 48:1398–1403

    PubMed  CAS  Google Scholar 

  • Daskalakis ZJ, Christensen BK, Fitzgerald PB, Chen R (2002) Transcranial magnetic stimulation: a new investigational and treatment tool in psychiatry. J Neuropsychiatry Clin Neurosci 14:406–415

    PubMed  Google Scholar 

  • Devanne H, Lavoie BA, Capaday C (1997) Input–output properties and gain changes in the human corticospinal pathway. Exp Brain Res 114:329–338

    Article  PubMed  CAS  Google Scholar 

  • Devanne H, Cohen LG, Kouchtir-Devanne N, Capaday C (2002) Integrated motor cortical control of task-related muscles during pointing in humans. J Neurophysiol 87:3006–3017

    PubMed  Google Scholar 

  • Di Lazzaro V, Oliviero A, Mazzone P, Pilato F, Saturno E, Dileone M, Insola A, Tonali PA, Rothwell JC (2002) Short-term reduction of intracortical inhibition in the human motor cortex induced by repetitive transcranial magnetic stimulation. Exp Brain Res 147:108–113

    Article  PubMed  CAS  Google Scholar 

  • Dominici F, Popa T, Ginanneschi F, Mazzocchio R, Rossi A (2005) Cortico-motoneuronal output to intrinsic hand muscles is differentially influenced by static changes in shoulder positions. Exp Brain Res 164:500–504

    Article  PubMed  CAS  Google Scholar 

  • Fitzgerald PB, Brown TL, Daskalakis ZJ, Chen R, Kulkarni J (2002) Intensity-dependent effects of 1 Hz rTMS on human corticospinal excitability. Clin Neurophysiol 113:1136–1141

    Article  PubMed  Google Scholar 

  • Fregni F, Pascual-Leone A (2007) Technology insight: noninvasive brain stimulation in neurology-perspectives on the therapeutic potential of rTMS and tDCS. Nat Clin Pract Neurol 3:383–93

    Article  PubMed  Google Scholar 

  • Gangitano M, Valero-Cabre A, Tormos JM, Mottaghy FM, Romero JR, Pascual-Leone A (2002) Modulation of input-output curves by low and high frequency repetitive transcranial magnetic stimulation of the motor cortex. Clin Neurophysiol 113:1249–1257

    Article  PubMed  Google Scholar 

  • Gerschlager W, Siebner HR, Rothwell JC (2001) Decreased corticospinal excitability after subthreshold 1 Hz rTMS over lateral premotor cortex. Neurology 57:449–455

    PubMed  CAS  Google Scholar 

  • 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 551:563–573

    Article  PubMed  CAS  Google Scholar 

  • Hallett M, Wassermann EM, Pascual-Leone A, Valls-Sole J (1999) Repetitive transcranial magnetic stimulation. Electroencephalogr Clin Neurophysiol Suppl 52:105–113

    PubMed  CAS  Google Scholar 

  • Houdayer E, Devanne H, Tyvaert L, Defebvre L, Derambure P, Cassim F (2007) Low frequency repetitive transcranial magnetic stimulation over premotor cortex can improve cortical tremor. Clin Neurophysiol 118:1557–1562

    Article  PubMed  CAS  Google Scholar 

  • Khedr EM, Farweez HM, Islam H (2003) Therapeutic effect of repetitive transcranial magnetic stimulation on motor function in Parkinson’s disease patients. Eur J Neurol 10:567–572

    Article  PubMed  CAS  Google Scholar 

  • Khedr EM, Rothwell JC, Ahmed MA, Shawky OA, Farouk M (2007) Modulation of motor cortical excitability following rapid-rate transcranial magnetic stimulation. Clin Neurophysiol 118:140–145

    Article  PubMed  Google Scholar 

  • Lang N, Siebner HR, Ernst D, Nitsche MA, Paulus W, Lemon RN, Rothwell JC (2004) Preconditioning with transcranial direct current stimulation sensitizes the motor cortex to rapid-rate transcranial magnetic stimulation and controls the direction of after-effects. Biol Psychiatry 56:634–639

    Article  PubMed  Google Scholar 

  • Lefaucheur JP, Drouot X, Von Raison F, Menard-Lefaucheur I, Cesaro P, Nguyen JP (2005) Improvement of motor performance and modulation of cortical excitability by repetitive transcranial magnetic stimulation of the motor cortex in Parkinson’s disease. Clin Neurophysiol 115:2530–2541

    Article  Google Scholar 

  • Maeda F, Keenan JP, Tormos JM, Topka H, Pascual-Leone A (2000a) Interindividual variability of the modulatory effects of repetitive transcranial magnetic stimulation on cortical excitability. Exp Brain Res 133:425–430

    Article  PubMed  CAS  Google Scholar 

  • Maeda F, Keenan JP, Tormos JM, Topka H, Pascual-Leone A (2000b) Modulation of corticospinal excitability by repetitive transcranial magnetic stimulation. Clin Neurophysiol 111:800–805

    Article  PubMed  CAS  Google Scholar 

  • Misawa S, Kuwabara S, Shibuya K, Mamada K, Hattori T (2005) Low-frequency transcranial magnetic stimulation for epilepsia partialis continua due to cortical dysplasia. J Neurol Sci 234:37–39

    Article  PubMed  Google Scholar 

  • 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 111:1002–1007

    Article  PubMed  CAS  Google Scholar 

  • Münchau A, Bloem BR, Irlbacher K, Trimble MR, Rothwell JC (2002) Functional connectivity of human premotor and motor cortex explored with repetitive transcranial magnetic stimulation. J Neurosci 22:554–561

    PubMed  Google Scholar 

  • Pal PK, Hanajima R, Gunraj CA, Li JY, Wagle-Shukla A, Morgante F, Chen R (2005) Effect of low-frequency repetitive transcranial magnetic stimulation on interhemispheric inhibition. J Neurophysiol 94:1668–1675

    Article  PubMed  Google Scholar 

  • Pascual-Leone A, Valls-Solè J, Brasil-Neto JP, Cammarota A, Grafman J, Hallett M (1994a) Akinesia in Parkinson’s disease. II: Effects of subthreshold repetitive transcranial motor cortex stimulation. Neurology 44:892–898

    PubMed  CAS  Google Scholar 

  • Pascual-Leone A, Valls-Solè J, Brasil-Neto JP, Cohen LG, Hallett M (1994b) Akinesia in Parkinson’s disease. I: shortening of simple reaction time with focal, single-pulse transcranial magnetic stimulation. Neurology 44: 884–891

    PubMed  CAS  Google Scholar 

  • Pascual-Leone A, Valls-Sole J, Wassermann EM, Hallett M (1994c) Responses to rapid-rate transcranial magnetic stimulation of the human motor cortex. Brain 117:847–858

    Article  PubMed  Google Scholar 

  • Peinemann A, Reimer B, Löer C, Quartarone A, Münchau A, Conrad B, Siebner HR (2004) Long-lasting increase in corticospinal excitability after 1800 pulses of subthreshold 5 Hz repetitive TMS to the primary motor cortex. Clin Neurophysiol 115:1519–1526

    Article  PubMed  Google Scholar 

  • Pitcher JB, Ogston KM, Miles TS (2003) Age and sex differences in human motor cortex input-output characteristics. J Physiol 546:605–613

    Article  PubMed  CAS  Google Scholar 

  • Plewnia C, Lotze M, Gerloff C (2003) Disinhibition of the contralateral motor cortex by low-frequency rTMS. Neuroreport 14:609–612

    Article  PubMed  Google Scholar 

  • Press WH, Flannery BP, Teukolsky SA, Vetterling WT (1986) Numerical recipes. Cambridge University Press, Cambridge

    Google Scholar 

  • Ridding MC, Rothwell JC (1997) Stimulus/response curves as a method of measuring motor cortical excitability in man. Electroencephalogr Clin Neurophysiol 105:340–344

    Article  PubMed  CAS  Google Scholar 

  • Rizzo V, Siebner HR, Modugno N, Pesenti A, Münchau A, Gerschlager W, Webb RM, Rothwell JC (2003) Shaping the excitability of human motor cortex with premotor rTMS. J Physiol 554:483–495

    Article  PubMed  Google Scholar 

  • Romero JR, Anschel D, Sparing R, Gangitano M, Pascual-Leone A (2002) Subthreshold low frequency repetitive transcranial magnetic stimulation selectively decreases facilitation in the motor cortex. Clin Neurophysiol 113:101–107

    Article  PubMed  Google Scholar 

  • Rossi S, Ulivelli M, Bartalani S, Galli R, Passero S, Battistini N, Vatti G (2004) Reduction of cortical myoclonus-related epileptic activity following slow-frequency rTMS. A case study. Neuroreport 15:293–296

    Article  PubMed  Google Scholar 

  • Siebner HR, Tormos JM, Ceballos-Baumann AO, Auer C, Catala MD, Conrad B, Pascual-Leone A (1999) Low-frequency repetitive transcranial magnetic stimulation of the motor cortex in writer’s cramp. Neurology 52:529–537

    PubMed  CAS  Google Scholar 

  • Siebner HR, Mentschel C, Auer C, Lehner C, Conrad B (2000a) Repetitive transcranial magnetic stimulation causes a short-term increase in the duration of the cortical silent period in patients with Parkinson’s disease. Neurosci Lett 284:147–150

    Article  PubMed  CAS  Google Scholar 

  • Siebner HR, Rossmeier C, Mentschel C, Peinemann A, Conrad B (2000b) Short-term motor improvement after sub-threshold 5-Hz repetitive transcranial magnetic stimulation of the primary motor hand area in Parkinson’s disease. J Neurol Sci 178:91–94

    Article  PubMed  CAS  Google Scholar 

  • Siebner HR, Filipovic SR, Rowe JB, Cordivari C, Gerschlager W, Rothwell JC, Frackowiak RS, Bhatia KP (2003) Patients with focal arm dystonia have increased sensitivity to slow-frequency repetitive TMS of the dorsal premotor cortex. Brain 126:2710–2725

    Article  PubMed  Google Scholar 

  • 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 24:3379–3385

    Article  PubMed  CAS  Google Scholar 

  • Sommer M, Wu T, Tergau F, Paulus W (2002) Intra- and interindividual variability of motor responses to repetitive transcranial magnetic stimulation. Clin Neurophysiol 113:265–269

    Article  PubMed  CAS  Google Scholar 

  • Touge T, Gerschlager W, Brown P, Rothwell JC (2001) Are the after-effects of low-frequency rTMS on motor cortex excitability due to changes in the efficacy of cortical synapses?. Clin Neurophysiol 112:2138–2145

    Article  PubMed  CAS  Google Scholar 

  • Tsuji T, Rothwell JC (2002) Long lasting effects of rTMS and associated peripheral sensory input on MEPs, SEPs and transcortical reflex excitability in humans. J Physiol 540:367–376

    Article  PubMed  CAS  Google Scholar 

  • Wassermann EM, Wedegaertner FR, Ziemann U, George MS, Chen R (1998) Crossed reduction of human motor cortex excitability by 1-Hz transcranial magnetic stimulation. Neurosci Lett 250:141–144

    Article  PubMed  CAS  Google Scholar 

  • Ziemann U (2004) TMS induced plasticity in human cortex. Rev Neurosci 15:253–266

    PubMed  Google Scholar 

  • Ziemann U, Lonnecker S, Steinhoff BJ, Paulus W (1996) Effects of antiepileptic drugs on motor cortex excitability in humans: a transcranial magnetic stimulation study. Ann Neurol. 40:367–378

    Article  PubMed  CAS  Google Scholar 

  • Ziemann U, Hallett M, Cohen LG (1998) Mechanisms of deafferentation-induced plasticity in human motor cortex. J Neurosci 18:7000–7007

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Elise Houdayer received a doctoral studentship from the Nord-Pas de Calais Regional Council and the Centre Hospitalier Universitaire de Lille (Lille University Medical Center). The authors wish to thank David Fraser for helpful comments on the manuscript’s English.

Author information

Authors and Affiliations

  1. Département de Neurophysiologie Clinique, Hôpital Roger Salengro, Centre Hospitalier Régional Universitaire, EA 2683, 59037, Lille cedex, France

    E. Houdayer, A. Degardin, F. Cassim, P. Bocquillon, P. Derambure & H. Devanne

  2. Université du Littoral Côte d’Opale, BP 699, 62228, Calais cedex, France

    H. Devanne

Authors
  1. E. Houdayer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Degardin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. Cassim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. Bocquillon
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P. Derambure
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. H. Devanne
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H. Devanne.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Houdayer, E., Degardin, A., Cassim, F. et al. The effects of low- and high-frequency repetitive TMS on the input/output properties of the human corticospinal pathway. Exp Brain Res 187, 207–217 (2008). https://doi.org/10.1007/s00221-008-1294-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00221-008-1294-z

Keywords

Search

Navigation