Experimental Brain Research

, Volume 194, Issue 4, pp 517–526 | Cite as

Electrophysiological correlates of short-latency afferent inhibition: a combined EEG and TMS study

  • Rozaliya Bikmullina
  • Dubravko Kičić
  • Synnöve Carlson
  • Vadim V. Nikulin
Research Article


Cutaneous stimulation produces short-latency afferent inhibition (SAI) of motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS). Since the demonstration of SAI is primarily based on the attenuation of MEPs, its cortical origin is not yet fully understood. In the present study we combined TMS with concurrent electroencephalography (EEG) in order to obtain direct cortical correlates of SAI. TMS-evoked EEG responses and MEPs were analysed with and without preceding electrical stimulation of the index finger cutaneous afferents in ten healthy volunteers. We show that the attenuation of MEPs by cutaneous stimulation has its counterpart in the attenuation of the N100 EEG response. Moreover, the attenuation of the cortical N100 component correlated positively with the strength of SAI, indicating that the transient changes in cortical excitability can be reflected in the amplitude dynamics of MEPs. We hypothesize that the hyperpolarization of the pyramidal cells due to SAI lowers the capacity of TMS to induce the inhibitory current needed to elicit N100, thus leading to its attenuation. We suggest that the observed interaction of two inhibitory processes, SAI and N100, provides further evidence for the cortical origin of SAI.


Short-latency afferent inhibition TMS-evoked EEG response Motor cortex 



Index finger






Event-related potentials


First dorsal interosseous


γ-Aminobutyric acid type A and type B receptors


Motor-evoked potential


Region of interest


Short-latency afferent inhibition


Transcranial magnetic stimulation



This study was supported by Centre for International Mobility (CIMO, Finland), Instrumentarium Science Foundation (Finland), Signe and Ane Gyllenberg Foundation (Finland), and the Academy of Finland (National Center of Excellence Program and the Neuro Program). Dr Vadim V. Nikulin was supported by the Berlin Bernstein Center for Computational Neuroscience. We are grateful to Dr. Ilkka Linnankoski for his comments on language.


  1. Barth D, Sutherling W (1988) Current source-density and neuromagnetic analysis of the direct cortical response in rat cortex. Brain Res 450:280–294PubMedCrossRefGoogle Scholar
  2. Bender S, Basseler K, Sebastian I, Resch F, Kammer T, Oelkers-Ax R, Weisbrod M (2005) Electroencephalographic response to transcranial magnetic stimulation in children: evidence for giant inhibitory potentials. Ann Neurol 58:58–67PubMedCrossRefGoogle Scholar
  3. Bonato C, Miniussi C, Rossini PM (2006) Transcranial magnetic stimulation and cortical evoked potentials: a TMS/EEG co-registration study. Clin Neurophysiol 117:1699–1707PubMedCrossRefGoogle Scholar
  4. Chambers CD, Payne JM, Stokes MG, Mattingley JB (2004) Fast and slow parietal pathways mediate spatial attention. Nat Neurosci 7:217–218PubMedCrossRefGoogle Scholar
  5. Classen J, Steinfelder B, Liepert J, Stefan K, Celnik P, Cohen LG, Hess A, Kunesch E, Chen R, Benecke R, Hallett M (2000) Cutaneomotor integration in humans is somatotopically organized at various levels of the nervous system and is task dependent. Exp Brain Res 130:48–59PubMedCrossRefGoogle Scholar
  6. Connors BW, Malenka RC, Silva LR (1988) Two inhibitory postsynaptic potentials, and GABAA and GABAB receptor-mediated responses in neocortex of rat and cat. J Physiol (Lond) 406:443–468Google Scholar
  7. Cucurachi L, Immovilli P, Granella F, Pavesi G, Cattaneo L (2008) Short-latency afferent inhibition predicts verbal memory performance in patients with multiple sclerosis. J NeurolGoogle Scholar
  8. Daskalakis ZJ, Paradiso GO, Christensen BK, Fitzgerald PB, Gunraj C, Chen R (2004) Exploring the connectivity between the cerebellum and motor cortex in humans. J Physiol 557:689–700PubMedCrossRefGoogle Scholar
  9. Delwaide PJ, Olivier E (1990) Conditioning transcranial cortical stimulation (TCCS) by exteroceptive stimulation in parkinsonian patients. Adv Neurol 53:175–181PubMedGoogle Scholar
  10. Di Lazzaro V, Oliviero A, Profice P, Pennisi MA, Di Giovanni S, Zito G, Tonali P, Rothwell JC (2000) Muscarinic receptor blockade has differential effects on the excitability of intracortical circuits in the human motor cortex. Exp Brain Res 135:455–461PubMedCrossRefGoogle Scholar
  11. Di Lazzaro V, Pilato F, Dileone M, Profice P, Ranieri F, Ricci V, Bria P, Tonali PA, Ziemann U (2007) Segregating two inhibitory circuits in human motor cortex at the level of GABAA receptor subtypes: a TMS study. Clin Neurophysiol 118:2207–2214PubMedCrossRefGoogle Scholar
  12. Edgley SA, Eyre JA, Lemon RN, Miller S (1997) Comparison of activation of corticospinal neurons and spinal motor neurons by magnetic and electrical transcranial stimulation in the lumbosacral cord of the anaesthetized monkey. Brain 120:839–853PubMedCrossRefGoogle Scholar
  13. Esser SK, Huber R, Massimini M, Peterson MJ, Ferrarelli F, Tononi G (2006) A direct demonstration of cortical LTP in humans: a combined TMS/EEG study. Brain Res Bull 69:86–94PubMedCrossRefGoogle Scholar
  14. Fitzgerald PB, Brown TL, Daskalakis ZJ, Chen R, Kulkarni J (2002) Intensity-dependent effects of 1 Hz rTMS on human corticospinal excitability. Clin Neurophysiol 113:1136–1141PubMedCrossRefGoogle Scholar
  15. Fuggetta G, Fiaschi A, Manganotti P (2005) Modulation of cortical oscillatory activities induced by varying single-pulse transcranial magnetic stimulation intensity over the left primary motor area: a combined EEG and TMS study. Neuroimage 27:896–908PubMedCrossRefGoogle Scholar
  16. Helmich RC, Bäumer T, Siebner HR, Bloem BR, Münchau A (2005) Hemispheric asymmetry and somatotopy of afferent inhibition in healthy humans. Exp Brain Res 167:211–219PubMedCrossRefGoogle Scholar
  17. Hess CW, Mills KR, Murray NM, Schriefer TN (1987) Excitability of the human motor cortex is enhanced during REM sleep. Neurosci Lett 82:47–52PubMedCrossRefGoogle Scholar
  18. Hortobagyi T, del Olmo MF, Rothwell JC (2006) Age reduces cortical reciprocal inhibition in humans. Exp Brain Res 171:322–329PubMedCrossRefGoogle Scholar
  19. Ilmoniemi RJ, Virtanen J, Ruohonen J, Karhu J, Aronen HJ, Näätänen R, Katila T (1997) Neuronal responses to magnetic stimulation reveal cortical reactivity and connectivity. Neuroreport 8:3537–3540PubMedCrossRefGoogle Scholar
  20. Kähkönen S, Wilenius J (2007) Effects of alcohol on TMS-evoked N100 responses. J Neurosci Methods 166:104–108PubMedCrossRefGoogle Scholar
  21. Kähkönen S, Komssi S, Wilenius J, Ilmoniemi RJ (2005) Prefrontal transcranial magnetic stimulation produces intensity-dependent EEG responses in humans. Neuroimage 24:955–960PubMedCrossRefGoogle Scholar
  22. Kičić D, Lioumis P, Ilmoniemi RJ, Nikulin VV (2008) Bilateral changes in excitability of sensorimotor cortices during unilateral movement: combined electroencephalographic and transcranial magnetic stimulation study. Neuroscience 152:1119–1129PubMedCrossRefGoogle Scholar
  23. Kimiskidis VK, Papagiannopoulos S, Kazis DA, Vasiliadis G, Oikonomidi A, Sotirakoglou K, Pseftogianni D, Anogianakis G, Vlaikidis N (2008) Silent period (SP) to transcranial magnetic stimulation: the EEG substrate. Brain Stimulation 1. Abstracts from the 3rd international conference on transcranial magnetic stimulation and direct current stimulation, 1–4 October 2008, pp 315–316Google Scholar
  24. Komssi S, Aronen HJ, Huttunen J, Kesaniemi M, Soinne L, Nikouline VV, Ollikainen M, Roine RO, Karhu J, Savolainen S, Ilmoniemi RJ (2002) Ipsi- and contralateral EEG reactions to transcranial magnetic stimulation. Clin Neurophysiol 113:175–184PubMedCrossRefGoogle Scholar
  25. Komssi S, Kähkönen S, Ilmoniemi RJ (2004) The effect of stimulus intensity on brain responses evoked by transcranial magnetic stimulation. Hum Brain Mapp 21:154–164PubMedCrossRefGoogle Scholar
  26. Komssi S, Savolainen P, Heiskala J, Kähkönen S (2007) Excitation threshold of the motor cortex estimated with transcranial magnetic stimulation electroencephalography. Neuroreport 18:13–16PubMedCrossRefGoogle Scholar
  27. Krnjević K, Randić M, Straughan DW (1966) An inhibitory process in the cerebral cortex. J Physiol 184:16–48PubMedGoogle Scholar
  28. Lioumis P, Kičić D, Savolainen P, Mäkelä JP, Kähkönen S (2008) Reproducibility of TMS-evoked EEG responses. Hum Brain Mapp: [Epub ahead of print]Google Scholar
  29. Markram H, Toledo-Rodriguez M, Wang Y, Gupta A, Silberberg G, Wu C (2004) Interneurons of the neocortical inhibitory system. Nat Rev Neurosci 5:793–807PubMedCrossRefGoogle Scholar
  30. Marzi CA, Mancini F, Savazzi S (2008) Interhemispheric transfer of phosphenes generated by occipital versus parietal transcranial magnetic stimulation. Exp Brain Res 192(3):431–441PubMedCrossRefGoogle Scholar
  31. Massimini M, Ferrarelli F, Huber R, Esser SK, Singh H, Tononi G (2005) Breakdown of cortical effective connectivity during sleep. Science 309:2228–2232PubMedCrossRefGoogle Scholar
  32. Matsunaga K, Akamatsu N, Uozumi T, Urasaki E, Tsuji S (2002) Early and late inhibition in the human motor cortex studied by paired stimulation through subdural electrodes. Clin Neurophysiol 113:1099–1109PubMedCrossRefGoogle Scholar
  33. McDonnell MN, Orekhov Y, Ziemann U (2006) The role of GABAB receptors in intracortical inhibition in the human motor cortex. Exp Brain Res 173:86–93PubMedCrossRefGoogle Scholar
  34. Mochizuki H, Terao Y, Okabe S, Furubayashi T, Arai N, Iwata NK, Hanajima R, Kamakura K, Motoyoshi K, Ugawa Y (2004) Effects of motor cortical stimulation on the excitability of contralateral motor and sensory cortices. Exp Brain Res 158:519–526PubMedCrossRefGoogle Scholar
  35. Näätänen R, Picton T (1987) The N1 wave of the human electric and magnetic response to sound: a review and an analysis of the component structure. Psychophysiology 24:375–425PubMedCrossRefGoogle Scholar
  36. Nardone R, Bergmann J, Kronbichler M, Kunz A, Klein S, Caleri F, Tezzon F, Ladurner G, Golaszewski S (2008) Abnormal short latency afferent inhibition in early Alzheimer’s disease: a transcranial magnetic demonstration. J Neural Transm 115:1557–1562PubMedCrossRefGoogle Scholar
  37. Nikouline V, Ruohonen J, Ilmoniemi RJ (1999) The role of the coil click in TMS assessed with simultaneous EEG. Clin Neurophysiol 110:1325–1328PubMedCrossRefGoogle Scholar
  38. Nikulin VV, Kičić D, Kähkönen S, Ilmoniemi RJ (2003) Modulation of electroencephalographic responses to transcranial magnetic stimulation: evidence for changes in cortical excitability related to movement. Eur J Neurosci 18:1206–1212PubMedCrossRefGoogle Scholar
  39. Paus T, Sipilä PK, Strafella AP (2001) Synchronization of neuronal activity in the human primary motor cortex by transcranial magnetic stimulation: an EEG study. J Neurophysiol 86:1983–1990PubMedGoogle Scholar
  40. Ponton CW, Vasama JP, Tremblay K, Khosla D, Kwong B, Don M (2001) Plasticity in the adult human central auditory system: evidence from late-onset profound unilateral deafness. Hear Res 154:32–44PubMedCrossRefGoogle Scholar
  41. Raij T, Karhu J, Kičić D, Lioumis P, Julkunen P, Lin FH, Ahveninen J, Ilmoniemi RJ, Mäkelä JP, Hämäläinen M, Rosen BR, Belliveau JW (2008) Parallel input makes the brain run faster. Neuroimage 40:1792–1797PubMedCrossRefGoogle Scholar
  42. Roick H, von Giesen HJ, Benecke R (1993) On the origin of the postexcitatory inhibition seen after transcranial magnetic brain stimulation in awake human subjects. Exp Brain Res 94:489–498PubMedCrossRefGoogle Scholar
  43. Romei V, Brodbeck V, Michel C, Amedi A, Pascual-Leone A, Thut G (2008) Spontaneous fluctuations in posterior alpha-band EEG activity reflect variability in excitability of human visual areas. Cereb Cortex 18:2010–2018PubMedCrossRefGoogle Scholar
  44. Rosenthal J, Waller HJ, Amassian VE (1967) An analysis of the activation of motor cortical neurons by surface stimulation. J Neurophysiol 30:844–858PubMedGoogle Scholar
  45. Rossini PM, Barker AT, Berardelli A, Caramia MD, Caruso G, Cracco RQ, Dimitrijević MR, Hallett M, Katayama Y, Lücking 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
  46. Schürmann M, Nikouline VV, Soljanlahti S, Ollikainen M, Basar E, Ilmoniemi RJ (2001) EEG responses to combined somatosensory and transcranial magnetic stimulation. Clin Neurophysiol 112:19–24PubMedCrossRefGoogle Scholar
  47. Seyal M, Browne JK, Masuoka LK, Gabor AJ (1993) Enhancement of the amplitude of somatosensory-evoked potentials following magnetic pulse stimulation of the human brain. Electroencephalogr Clin Neurophysiol 88:20–27PubMedCrossRefGoogle Scholar
  48. Silvanto J, Muggleton NG, Cowey A, Walsh V (2007) Neural adaptation reveals state-dependent effects of transcranial magnetic stimulation. Eur J Neurosci 25:1874–1881PubMedCrossRefGoogle Scholar
  49. Talelli P, Cheeran BJ, Teo JT, Rothwell JC (2007) Pattern-specific role of the current orientation used to deliver Theta Burst Stimulation. Clin Neurophysiol 118:1815–1823PubMedCrossRefGoogle Scholar
  50. Tamas G, Lorincz A, Simon A, Szabadics J (2003) Identified sources and targets of slow inhibition in the neocortex. Science 299:1902–1905PubMedCrossRefGoogle Scholar
  51. Tamburin S, Manganotti P, Zanette G, Fiaschi A (2001) Cutaneomotor integration in human hand motor areas: somatotopic effect and interaction of afferents. Exp Brain Res 141:232–241PubMedCrossRefGoogle Scholar
  52. Thielscher A, Kammer T (2002) Linking physics with physiology in TMS: a sphere field model to determine the cortical stimulation site in TMS. Neuroimage 17:1117–1130PubMedCrossRefGoogle Scholar
  53. Thut G, Northoff G, Ives JR, Kamitani Y, Pfennig A, Kampmann F, Schomer DL, Pascual-Leone A (2003) Effects of single-pulse transcranial magnetic stimulation (TMS) on functional brain activity: a combined event-related TMS and evoked potential study. Clin Neurophysiol 114:2071–2080PubMedCrossRefGoogle Scholar
  54. Tiitinen H, Virtanen J, Ilmoniemi RJ, Kamppuri J, Ollikainen M, Ruohonen J, Näätänen R (1999) Separation of contamination caused by coil clicks from responses elicited by transcranial magnetic stimulation. Clin Neurophysiol 110:982–985PubMedCrossRefGoogle Scholar
  55. Tokimura H, Di Lazzaro V, Tokimura Y, Oliviero A, Profice P, Insola A, Mazzone P, Tonali P, Rothwell JC (2000) Short latency inhibition of human hand motor cortex by somatosensory input from the hand. J Physiol (Lond) 523:503–513 Published erratum appears in J Physiol (Lond) 2000 May 1;524 Pt 3:942CrossRefGoogle Scholar
  56. Valls-Solé J, Pascual-Leone A, Wassermann EM, Hallett M (1992) Human motor-evoked responses to paired transcranial magnetic stimuli. Electroencephalogr Clin Neurophysiol 85:355–364PubMedCrossRefGoogle Scholar
  57. Werhahn KJ, Kunesch E, Noachtar S, Benecke R, Classen J (1999) Differential effects on motorcortical inhibition induced by blockade of GABA uptake in humans. J Physiol (Lond) 517:591–597CrossRefGoogle Scholar
  58. Ziemann U, Muellbacher W, Hallett M, Cohen LG (2001) Modulation of practice-dependent plasticity in human motor cortex. Brain 124:1171–1181PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Rozaliya Bikmullina
    • 1
  • Dubravko Kičić
    • 1
    • 2
  • Synnöve Carlson
    • 3
    • 4
    • 5
  • Vadim V. Nikulin
    • 6
    • 7
  1. 1.BioMag Laboratory-HUSLABHospital District of Helsinki and UusimaaHelsinkiFinland
  2. 2.Department of Biomedical Engineering and Computational ScienceHelsinki University of TechnologyTKKFinland
  3. 3.Neuroscience Unit, Institute of Biomedicine/PhysiologyUniversity of HelsinkiHelsinkiFinland
  4. 4.Brain Research Unit, Low Temperature LaboratoryHelsinki University of TechnologyEspooFinland
  5. 5.Medical SchoolUniversity of TampereTampereFinland
  6. 6.Neurophysics Group, Department of Neurology and Clinical NeurophysiologyCampus Benjamin Franklin-Charité, University Medicine BerlinBerlinGermany
  7. 7.Bernstein Center for Computational NeuroscienceBerlinGermany

Personalised recommendations