Documenta Ophthalmologica

, 123:65 | Cite as

Spatial frequency differentially affects habituation in migraineurs: a steady-state visual-evoked potential study

  • Koichi Shibata
  • Kiyomi Yamane
  • Yoshiko Nishimura
  • Hiromi Kondo
  • Kuniaki Otuka
Original Research Article


A lack of habituation in visual-evoked potentials (VEPs) is the main abnormality observed in migraineurs. However, no study of steady-state VEPs has yet evaluated pattern-reversal stimuli with respect to habituation behavior or spatial frequency. The aim of this study was to clarify habituation behavior in migraineurs between attacks and to establish characteristics of VEPs in these patients. Steady-state VEPs were sequentially recorded as checkerboard patterns in four consecutive blocks from 12 patients with migraine without aura (MO), 12 patients with migraine with aura (MA), and 12 healthy controls (HC) at four spatial frequencies of 0.5, 1.0, 2.0, and 4.0 cycles per degree (cpd) with a stimulus rate of 7.5 Hz (15 reversal/s). VEP amplitudes were consistently higher in migraineurs. However, habituation was not demonstrated in HCs, and migraineurs did not reveal a clear lack of habituation. MAs exhibited high-amplitude VEPs, depending on spatial frequency. In the MA patients, amplitude differences reached statistical significance at 2.0 cpd. The sequential amplitude changes at 0.5 cpd were significantly different in MAs compared with HCs. Migraine patients exhibited high-amplitude VEPs, which were dependent on spatial frequency, and may be related to altered excitability in pre-cortical and cortical visual processing.


Migraine Visual-evoked potential Habituation Spatial frequency Visual processing Hyperreactivity 


  1. 1.
    Welch KM (2003) Contemporary concepts of migraine pathogenesis. Neurology 61:S2–S8PubMedGoogle Scholar
  2. 2.
    Berger M, Speckmann E-J, Pape HC, Gorji A (2008) Spreading depression enhances human neocortical excitability in vitro. Cephalalgia 28:558–562PubMedCrossRefGoogle Scholar
  3. 3.
    Schoenen J, Wang W, Albert A, Delwaide PJ (1995) Potentiation instead of habituation characterizes visual evoked potentials in migraine patients between attack. Eur J Neurol 2:115–122CrossRefGoogle Scholar
  4. 4.
    Áfra J, Cecchini AP, De Pasqua V, Albert A, Schoenen J (1998) Visual evoked potentials during long periods of pattern-reversal stimulation in migraine. Brain 121:233–241PubMedCrossRefGoogle Scholar
  5. 5.
    Sándor PS, Áfra J, Cecchini AP, Albert A, Schoenen J (1999) Familial influences on cortical evoked potentials in migraine. Neuroreport 26:1235–1238CrossRefGoogle Scholar
  6. 6.
    Wang W, Wang GP, Ding XL, Wang YH (1999) Personality and response to repeated visual stimulation in migraine and tension-type headaches. Cephalalgia 19:718–724PubMedCrossRefGoogle Scholar
  7. 7.
    Bohotin V, Fumal A, Vandenheede M, Gérard 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
  8. 8.
    Fumal A, Coppola G, Bohotin V, Gérardy PY, Seidel L, Donneau AF, Vandenheede M, Maertens de Noordhout A, Schoenen J (2006) Induction of long-lasting changes of visual cortex excitability by five daily sessions repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers and migraine patients. Cephalalgia 26:143–149PubMedCrossRefGoogle Scholar
  9. 9.
    Coppola G, Ambrosini A, Di Clemete L, Magis D, Fumal A, Gérard P, Pierelli F, Schoenen J (2007) Interictal abnormalities of gamma band activity in visual evoked responses in migraine: an indication of thalamocortical dysfunction? Cephalalgia 27:1323–1330CrossRefGoogle Scholar
  10. 10.
    Magis D, Allena M, Coppola G, Di Clemente L, Gérard P, Schoenen J (2007) Search for correlations between genotypes and electrophysiological patterns in migraine: the MTHFR C677T polymorphism and visual evoked potentials. Cephalalgia 27:1142–1149Google Scholar
  11. 11.
    Schoenen J, Ambrosini A, Sándor PS, de Noordhout AM (2003) Evoked potentials and transcranial magnetic stimulation in migraine: published data and viewpoint on their pathophysiologic significance. Clin Neurophysiol 114:955–972PubMedCrossRefGoogle Scholar
  12. 12.
    Coppola G, Pierelli F, Schoenen J (2007) Is the cerebral cortex hyperexcitable or hyperresponsive in migraine? Cephalalgia 27:1429–1439Google Scholar
  13. 13.
    Shibata K, Osawa M, Iwata I (1997) Pattern reversal visual evoked potentials in classic and common migraine. J Neurol Sci 145:177–181PubMedCrossRefGoogle Scholar
  14. 14.
    Oelkers R, Grosser K, Lang E, Geisslinger G, Kobal G, Brune K, Lötsch J (1999) Visual evoked potentials in migraine patients: alterations depend on pattern spatial frequency. Brain 122:1147–1155PubMedCrossRefGoogle Scholar
  15. 15.
    Sand T, Zhiniy N, White LR, Stovner LJ (2008) Visual evoked potential latency, amplitude and habituation in migraine: a longitudinal study. Clin Neurophysiol 119:1020–1027PubMedCrossRefGoogle Scholar
  16. 16.
    Simon RH, Zimmerman AW, Tasman A, Hale MS (1982) Spectral analysis of photic stimulation in migraine. Electroencephalogr Clin Neurophysiol 53:270–276PubMedCrossRefGoogle Scholar
  17. 17.
    Nyrke T, Lang AH (1982) Spectral analysis of visual potentials evoked by sine wave modulated light in migraine. Electroencephalogr Clin Neurophysiol 53:436–442PubMedCrossRefGoogle Scholar
  18. 18.
    Nyrke T, Kangasniemi P, Lang AH, Petersen E (1984) Steady-state visual evoked potentials during migraine prophylaxis by propranolol and femoxetine. Acta Neurol Scand 69:9–14PubMedCrossRefGoogle Scholar
  19. 19.
    Nyrke T, Kangasniemi P, Lang AH (1989) Difference of steady-state visual evoked potentials in classic and common migraine. Electroencephalogr Clin Neurophysiol 73:285–294PubMedCrossRefGoogle Scholar
  20. 20.
    Nyrke T, Kangasniemi P, Lang AH (1990) Transient asymmetric of steady-state visual evoked potentials in classic migraine. Headache 30:133–137PubMedCrossRefGoogle Scholar
  21. 21.
    Genco D, de Tommaso N, Prudenzano AM, Savarese M, Puca FM (1994) EEG features in juvenile migraine: topographic analysis of spontaneous and visual evoked brain electrical activity: a comparison with adult migraine. Cephalalgia 14:41–46PubMedCrossRefGoogle Scholar
  22. 22.
    Puca FM, de Tommaso M, Tota P, Sciruicchio V (1996) Photic driving in migraine: correlations with clinical features. Cephalalgia 16:246–250PubMedCrossRefGoogle Scholar
  23. 23.
    de Tommaso M, Sciruicchio V, Guido M, Sasanelli G, Specchio LM, Puca FM (1998) EEG spectral analysis in migraine without aura attacks. Cephalalgia 18:324–328PubMedCrossRefGoogle Scholar
  24. 24.
    de Tommaso M, Sciruicchio V, Guido M, Sasanelli G, Puca F (1999) Steady-state visual-evoked potentials in headache: diagnostic value in migraine and tension-type headache patients. Cephalalgia 19:23–26PubMedCrossRefGoogle Scholar
  25. 25.
    de Tommaso M, Marinazzo D, Guido M, Libro G, Stramaglia S, Nitti L, Lattanzi G, Angelini L, Pellicoro M (2005) Visually evoked phase synchronization changes of alpha rhythm in migraine: correlations with clinical features. Int J Psychophysiol 57:203–210PubMedCrossRefGoogle Scholar
  26. 26.
    de Tommaso M, Marinazzo D, Nitti L, Pellicoro M, Guido M, Serpino C, Stramaglia S (2007) Effects of levetiracetam vs. topiramate and placebo on visually evoked phase synchronization changes of alpha rhythm in migraine. Clin Neurophysiol 118:2297–2304PubMedCrossRefGoogle Scholar
  27. 27.
    Angelini L, de Tommaso M, Guido M, Hu K, Ivanov PCh, Marinazzo D, Nardulli G, Nitti L, Pellicoro M, Pierro C, Stramaglia S (2004) Steady-state visual evoked potentials and phase synchronization in migraine patients. Phys Rev Lett 93:038103 1–4Google Scholar
  28. 28.
    de Tommaso M, Stramaglia S, Schoffelen JM, Guido M, Libro G, Losito L, Sciruicchio V, Sardaro M, Pellicoro M, Puca FM (2003) Steady-state visual evoked potentials in the low frequency range in migraine: a study of habituation and variability phenomena. Int J Psychophysiol 49:165–174PubMedCrossRefGoogle Scholar
  29. 29.
    Headache Classification Subcommittee of the International Headache Society (2004) The international classification of headache disorders, 2nd edn. Cephalalgia 24(suppl 1):1–160Google Scholar
  30. 30.
    Shibata K, Yamane K, Otuka K, Iwata M (2008) Abnormal visual processing in migraine with aura: a study of steady-state visual evoked potentials. J Neurol Sci 271:119–126PubMedCrossRefGoogle Scholar
  31. 31.
    Khalil NM, Legg NJ, Anderson DJ (2000) Long term decline of P100 amplitude in migraine aura. J Neurol Neurosurg Psychiatry 69:507–511PubMedCrossRefGoogle Scholar
  32. 32.
    Sand T, Vingen JV (2000) Visual, long-latency auditory and brainstem auditory evoked potentials in migraine: relation to pattern size, stimulus intensity, sound and light discomfort thresholds and pre-attack state. Cephalalgia 20:804–820PubMedCrossRefGoogle Scholar
  33. 33.
    Chen WT, Wang SJ, Fuh JL, Lin CP, Ko YC, Lin YY (2009) Peri-ictal normalization of visual cortex excitability in migraine: an MEG study. Cephalalgia 29:1202–1211PubMedCrossRefGoogle Scholar
  34. 34.
    Thompson RF, Spencer WA (1966) Habituation: a model phenomenon for the study of neuronal substrates of behavior. Psychol Rev 73:16–43PubMedCrossRefGoogle Scholar
  35. 35.
    Diener HC, Sholtz E, Dichgans J, Gerber WD, Jäck A, Bille A, Niederberger U (1989) Central effects of drugs used in migraine prophylaxis evaluated by visual evoked potentials. Ann Neurol 25:125–130PubMedCrossRefGoogle Scholar
  36. 36.
    Regan D (1989) Human brain electrophysiology; evoked potentials and evoked magnetic field in science and medicine. Elsevier, AmsterdamGoogle Scholar
  37. 37.
    Shibata K, Yamane K, Iwata M, Ohkawa S (2005) Evaluating the effects of spatial frequency on migraines by using pattern-reversal visual evoked potentials. Clin Neurophysiol 116:2220–2227PubMedCrossRefGoogle Scholar
  38. 38.
    Kennard C, Gawel M, Rudolph NM, Rose FC (1978) Visual evoked potentials in migraine subjects. Headache 6:73–80Google Scholar
  39. 39.
    Polich J, Ehlers CL, Dalessio DJ (1986) Pattern-shift visual evoked responses and EEG in migraine. Headache 26:451–456PubMedCrossRefGoogle Scholar
  40. 40.
    Mariani E, Moschini V, Pastorino G, Rizzi F, Severgnini A, Tiengo M (1988) Pattern-reversal visual evoked potentials and EEG correlations in common migraine patients. Headache 28:269–271PubMedCrossRefGoogle Scholar
  41. 41.
    Drake ME, Pakalnis A, Hietter SA, Padamandan H (1990) Visual and auditory evoked potentials in migraine. Electromyogr Clin Neurophysiol 30:77–81PubMedGoogle Scholar
  42. 42.
    Tagliati M, Sabbadini M, Bernardi G, Silvestrini M (1995) Multichannel visual evoked potentials in migraine. Electroencephalogr Clin Neurophysiol 96:1–5PubMedCrossRefGoogle Scholar
  43. 43.
    Sener HO, Haktanir I, Demirci S (1997) Pattern-reversal visual evoked potentials in migraineurs with or without aura. Headache 37:449–451PubMedCrossRefGoogle Scholar
  44. 44.
    Aurora SK, Barrodale P, Chronicle EP, Mulleners WM (2005) Cortical inhibition is reduced in chronic and episodic migraine and demonstrates a spectrum of illness. Headache 45:546–552PubMedCrossRefGoogle Scholar
  45. 45.
    Aurora SK, Wilkinson F (2007) The brain is hyperexcitable in migraine. Cephalalgia 27:1442–1453Google Scholar
  46. 46.
    Livingstone M, Hubel D (1988) Segregation of form, color, movement, and depth: anatomy, physiology, and perception. Science 240:740–749PubMedCrossRefGoogle Scholar
  47. 47.
    Bassi CJ, Lehmkuhle S (1990) Clinical implications of parallel visual pathways. J Am Optom Assoc 61:98–110PubMedGoogle Scholar
  48. 48.
    Khalil NM (1991) Investigations of visual function in migraine using visual evoked potentials and visual psychophysical tests. PhD thesis, University of LondonGoogle Scholar
  49. 49.
    Coleston DM, Chronicle E, Ruddock KH, Kennard C (1994) Precortical dysfunction of spatial and temporal visual processing in migraine. J Neurol Neurosurg Psychiatry 57:1208–1211PubMedCrossRefGoogle Scholar
  50. 50.
    Benedek K, Tajti J, Janáky M, Vécsei L, Benedek G (2002) Spatial contrast sensitivity of migraine patients without aura. Cephalalgia 22:142–145PubMedCrossRefGoogle Scholar
  51. 51.
    Huang J, Cooper TG, Satana B, Kaufman DI, Cao Y (2003) Visual distortion provoked by a stimulus in migraine associated with hyperneuronal activity. Headache 43:664–671PubMedCrossRefGoogle Scholar
  52. 52.
    Kowacs PA, Piovesan EJ, Werneck LC, Fameli H, Zani AC, da Silva HP (2005) Critical flicker frequency in migraine. A controlled study in patients without prophylactic therapy. Cephalalgia 25:339–343PubMedCrossRefGoogle Scholar
  53. 53.
    McKendrick AM, Badcock DR (2003) Contrast-processing dysfunction in both magnocellular and parvocellular pathways in migraineurs both with or without aura. Invest Ophthalmol Vis Sci 44:442–448PubMedCrossRefGoogle Scholar
  54. 54.
    McKendrick AM, Vingrys AJ, Badcock DR, Heywood JT (2001) Visual dysfunction between migraine events. Invest Ophthalmol Vis Sci 42:626–633PubMedGoogle Scholar
  55. 55.
    McKendrick AM, Sampson GP (2009) Low spatial frequency contrast sensitivity deficits in migraine are not visual pathway selective. Cephalalgia 29:539–549PubMedCrossRefGoogle Scholar
  56. 56.
    Harle DE, Evans BJW (2005) Frequency doubling technology perimetry and standard automated perimetry in migraine. Ophthal Physiol Opt 25:233–239CrossRefGoogle Scholar
  57. 57.
    Omland PM, Nilsen KB, Sand T (2011) Habituation measured by pattern reversal visual evoked potentials depends more on check size than reversal rate. Clin Neurophysiol (in press)Google Scholar
  58. 58.
    McKendrick AM, Badcock DR (2004) Motion processing deficits in migraine. Cephalalgia 24:363–372PubMedCrossRefGoogle Scholar
  59. 59.
    Porciatti V, Sartucci F (1999) Normative data for onset VEPs to red-green and blue-yellow chromatic contrast. Clin Neurophysiol 110:772–781PubMedCrossRefGoogle Scholar
  60. 60.
    Shibata K, Yamane K, Iwata M (2006) Change of excitability in brainstem and cortical visual processing in migraine exhibiting allodynia. Headache 46:1535–1544PubMedCrossRefGoogle Scholar
  61. 61.
    Kelly DH (1976) Pattern detection and the two-dimensional fourier transform: flickering checkerboards and chromatic mechanisms. Vis Res 16:277–287PubMedCrossRefGoogle Scholar
  62. 62.
    Schechter I, Butler P, Zemon VM, Revheim N, Saperstein AM, Jalbrzikowski M, Pasternak R, Silipo G, Javitt DC (2005) Impairments in generation of early-stage transient visual evoked potentials to magno- and parvocellular-selective stimuli in schizophrenia. Clin Neurophysiol 116:2204–2215PubMedCrossRefGoogle Scholar
  63. 63.
    Tobimatsu S, Celesia GG (2006) Studies of human visual pathophysiology with visual evoked potentials. Clin Neurophysiol 117:1414–1433PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Koichi Shibata
    • 1
  • Kiyomi Yamane
    • 2
  • Yoshiko Nishimura
    • 1
  • Hiromi Kondo
    • 1
  • Kuniaki Otuka
    • 1
  1. 1.Department of MedicineTokyo Women’s Medical UniversityTokyoJapan
  2. 2.Department of Neurology, Neurological InstituteOhta General HospitalFukushimaJapan

Personalised recommendations