Experimental Brain Research

, Volume 188, Issue 3, pp 427–435 | Cite as

Paired-pulse behavior of visually evoked potentials recorded in human visual cortex using patterned paired-pulse stimulation

  • Oliver Höffken
  • Torsten Grehl
  • Hubert R. Dinse
  • Martin Tegenthoff
  • Michael BachEmail author
Research Article


Paired-pulse stimulation techniques are used as common tools to investigate cortical excitability and cortical plastic changes. Similar to investigations in the somatosensory and motor system here we applied a new paired-pulse paradigm to study the paired-pulse behavior of visually evoked potentials (VEPs) in 25 healthy subjects. VEPs were recorded and the responses to the first and the second P100 peak were analyzed at different SOAs [stimulus onset asynchrony (SOA) = interstimulus interval (ISI) + pulse duration (13 ms)]. Two measures describe the paired pulse interaction: the “amplitude ratio”, the ratio of the second to the first amplitude, and the “latency shift”, the difference of the inter-peak interval between the P100 peaks and the respective SOA. To separate alterations in the amplitude of the second VEP response due to changes in paired-pulse inhibition from those originating from superposition of the two waveforms, particularly at short SOAs, we created a waveform template from recordings made at SOAs of 1 s, where interaction can be assumed to be negligible. Superposed traces of VEP recordings were then created by adding two templates at delays corresponding to the SOAs used. The original recordings were then digitally subtracted from the traces obtained by superposition. Analysis of the subtracted traces revealed evidence that at short SOAs the second VEP response is substantially suppressed, a finding comparable to the paired-pulse inhibition described for motor and somatosensory cortex following paired-pulse stimulation. However, paired-pulse inhibition seen in V1 varied considerably from subject to subject, both in respect to amplitude, and to time of maximal inhibition. We found paired-pulse inhibition ranging from 12 to 76% (mean 34%) at SOAs between 80 (shortest discriminable SOA) and 320 ms (mean 128 ms). At intermediate SOAs between 80 and 720 ms (mean 215 ms) the amplitude ratios were between 94 and 145% (mean 116%) indicative of slight paired-pulse facilitation. Comparable to recovery studies by means of paired-pulse median nerve stimulation in somatosensory cortex, at shorter SOAs we found a delayed second VEP response. Combined together, our findings suggest that VEPs are characterized by significant paired-pulse inhibition at short SOAs, a phenomenon reminiscent of findings reported in other modalities. Possible mechanisms and pharmacological properties of the described paired-pulse behavior in visual cortex remain to be explored.


Paired-pulse Excitability Plasticity Visual evoked potentials 


  1. Allison T (1962) Recovery functions of somatosensory evoked responses in man. Electroencephalogr Clin Neurophysiol 14:331–343PubMedCrossRefGoogle Scholar
  2. American Encephalographic Society (1994) Guideline thirteen: guidelines for standard electrode position nomenclature. J Clin Neurophysiol 11:111–113Google Scholar
  3. Bach M (2000) Freiburg evoked potentials. Accessed 19 September 2007
  4. Bach M, Meigen T, Strasburger H (1997) Raster-scan cathode-ray tubes for vision research—limits of resolution in space, time and intensity, and some solutions. Spat Vis 10:403–414PubMedCrossRefGoogle Scholar
  5. Bellingham MC, Walmsley B (1999) A novel presynaptic inhibitory mechanism underlies paired pulse depression at a fast central synapse. Neuron 23:159–170PubMedCrossRefGoogle Scholar
  6. Bohotin V, Fumal A, Vandenheede M, Gerard P, Bohotin C, Maertens de Noordhout A, Schoenen J (2002) Effects of repetitive transcranial magnetic stimulation on visual evoked potentials in migraine. Brain 125:912–922PubMedCrossRefGoogle Scholar
  7. Boroojerdi B, Bushara KO, Corwell B, Immisch I, Battaglia F, Muellbacher W, Cohen LG (2000) Enhanced excitability of the human visual cortex induced by short-term light deprivation. Cereb Cortex 10:529–534PubMedCrossRefGoogle Scholar
  8. Cohen LG, Ziemann U, Chen R, Classen J, Hallett M, Gerloff C, Butefisch C (1998) Studies of neuroplasticity with transcranial magnetic stimulation. J Clin Neurophysiol 15:305–324PubMedCrossRefGoogle Scholar
  9. David-Jurgens M, Dinse HR (2007) Age-related effects on cortical excitability as measured with paired pulse technique of neurons recorded in rat somatosensory cortex. Soc Neurosci Abstr (in press)Google Scholar
  10. Gerwig M, Niehaus L, Kastrup O, Stude P, Diener HC (2005) Visual cortex excitability in migraine evaluated by single and paired magnetic stimuli. Headache 45:1394–1399PubMedGoogle Scholar
  11. Greenwood PM, Goff WR (1987) Modification of median nerve somatic evoked potentials by prior median nerve, peroneal nerve, and auditory stimulation. Electroencephalogr Clin Neurophysiol 68:295–302PubMedCrossRefGoogle Scholar
  12. Hanajima R, Ugawa Y, Terao Y, Sakai K, Furubayashi T, Machii K, Kanazawa I (1998) Paired-pulse magnetic stimulation of the human motor cortex: differences among I waves. J Physiol 509(Pt 2):607–618PubMedCrossRefGoogle Scholar
  13. Hoffken O, Veit M, Knossalla F, Lissek S, Bliem B, Ragert P, Dinse HR, Tegenthoff M (2007) Sustained increase of somatosensory cortex excitability by tactile coactivation studied by paired median nerve stimulation in humans correlates with perceptual gain. J Physiol 584:463–471PubMedCrossRefGoogle Scholar
  14. Hoshiyama M, Kakigi R (2001) Two evoked responses with different recovery functions in the primary somatosensory cortex in humans. Clin Neurophysiol 112:1334–1342PubMedCrossRefGoogle Scholar
  15. Hoshiyama M, Kakigi R (2003) Changes in somatosensory evoked responses by repetition of the median nerve stimulation. Clin Neurophysiol 114:2251–2257PubMedCrossRefGoogle Scholar
  16. Ilic TV, Meintzschel F, Cleff U, Ruge D, Kessler KR, Ziemann U (2002) Short-interval paired-pulse inhibition and facilitation of human motor cortex: the dimension of stimulus intensity. J Physiol 545:153–167PubMedCrossRefGoogle Scholar
  17. Kammer T (1999) Phosphenes and transient scotomas induced by magnetic stimulation of the occipital lobe: their topographic relationship. Neuropsychologia 37:191–198PubMedCrossRefGoogle Scholar
  18. Klostermann F, Funk T, Vesper J, Siedenberg R, Curio G (2000) Double-pulse stimulation dissociates intrathalamic and cortical high-frequency (>400 Hz) SEP components in man. Neuroreport 11:1295–1299PubMedCrossRefGoogle Scholar
  19. Kong CK, Wong LY, Yuen MK (2000) Visual field plasticity in a female with right occipital cortical dysplasia. Pediatr Neurol 23:256–260PubMedCrossRefGoogle Scholar
  20. 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
  21. Liepert J, Classen J, Cohen LG, Hallett M (1998) Task-dependent changes of intracortical inhibition. Exp Brain Res 118:421–426PubMedCrossRefGoogle Scholar
  22. Liepert J, Storch P, Fritsch A, Weiller C (2000) Motor cortex disinhibition in acute stroke. Clin Neurophysiol 111:671–676PubMedCrossRefGoogle Scholar
  23. Musselwhite MJ, Jeffreys DA (1983) Visual evoked potentials to double-pulse pattern presentation. Vis Res 23:135–143PubMedCrossRefGoogle Scholar
  24. Odom JV, Bach M, Barber C, Brigell M, Marmor MF, Tormene AP, Holder GE, Vaegan (2004) Visual evoked potentials standard (2004). Doc Ophthalmol 108:115–123PubMedCrossRefGoogle Scholar
  25. Ragert P, Becker M, Tegenthoff M, Pleger B, Dinse HR (2004) Sustained increase of somatosensory cortex excitability by 5 Hz repetitive transcranial magnetic stimulation studied by paired median nerve stimulation in humans. Neurosci Lett 356:91–94PubMedCrossRefGoogle Scholar
  26. Romani A, Bergamaschi R, Versino M, Callieco R, Calabrese G, Cosi V (1995) Recovery functions of early cortical median nerve SSEP components: normative data. Electroencephalogr Clin Neurophysiol 96:475–478PubMedCrossRefGoogle Scholar
  27. Schwartz M, Shagass C (1964) Recovery functions of human somatosensory and visual evoked potentials. Ann N Y Acad Sci 112:510–525PubMedCrossRefGoogle Scholar
  28. Sparing R, Dambeck N, Stock K, Meister IG, Huetter D, Boroojerdi B (2005) Investigation of the primary visual cortex using short-interval paired-pulse transcranial magnetic stimulation (TMS). Neurosci Lett 382:312–316PubMedCrossRefGoogle Scholar
  29. Stevens CF, Wang Y (1995) Facilitation and depression at single central synapses. Neuron 14:795–802PubMedCrossRefGoogle Scholar
  30. Ziemann U, Rothwell JC, Ridding MC (1996) Interaction between intracortical inhibition and facilitation in human motor cortex. J Physiol 496(Pt 3):873–881PubMedGoogle Scholar
  31. Ziemann U, Corwell B, Cohen LG (1998) Modulation of plasticity in human motor cortex after forearm ischemic nerve block. J Neurosci 18:1115–1123PubMedGoogle Scholar
  32. Zucker RS (1989) Short-term synaptic plasticity. Annu Rev Neurosci 12:13–31PubMedCrossRefGoogle Scholar
  33. Zucker RS, Regehr WG (2002) Short-term synaptic plasticity. Annu Rev Physiol 64:355–405PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Oliver Höffken
    • 1
  • Torsten Grehl
    • 1
  • Hubert R. Dinse
    • 2
  • Martin Tegenthoff
    • 1
  • Michael Bach
    • 3
    Email author
  1. 1.Department of NeurologyRuhr-University Bochum, BG-Kliniken BergmannsheilBochumGermany
  2. 2.Neural Plasticity Lab, Institute for Neuroinformatics, Department of Theoretical BiologyRuhr-University BochumBochumGermany
  3. 3.Univ.-Augenklinik FreiburgFreiburgGermany

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