The Cerebellum

, Volume 8, Issue 3, pp 260–266 | Cite as

Reduced Cerebellar Inhibition in Migraine with Aura: A TMS Study

  • Filippo Brighina
  • Antonio Palermo
  • Maristella L. Panetta
  • Ornella Daniele
  • Antonina Aloisio
  • Giuseppe Cosentino
  • Brigida Fierro
Article

Abstract

Subtle clinical cerebellar alterations have been found in migraine. Moreover, abnormalities in visual and motor cortex excitability consistent with a lack of inhibitory efficiency have been described in migraine, and it is known that cerebellum exerts an inhibitory control on cerebral cortex. Here, we investigated if impairment of cerebellar activity on motor cortex, i.e. reduced inhibitory control, can be found in migraine. Ten migraineurs with aura and seven healthy controls underwent a transcranial magnetic stimulation (TMS) protocol to investigate the cerebellar inhibitory drive on motor cortex: a conditioning pulse on right cerebellar cortex was delivered 5, 7, 10, 15 ms before a test stimulus (TS) on contralateral motor cortex. The cerebellar conditioning stimulus inhibits the size of the motor-evoked potential (MEP) produced by the TS alone by approximately 30–50%. Amplitude of MEP to TS alone showed no significant difference between patients and controls. Cerebellar conditioning TMS showed a significant deficit of cerebellar inhibition in migraine patients as compared to controls at all interstimulus intervals (5–15 ms) tested. Cerebellar inhibition is reduced in migraineurs. This could account, at least in part, for the reduced inhibitory efficiency previously showed in cerebral cortex of these patients.

Keywords

Migraine Cerebellum TMS Test stimulus Cerebellar brain inhibition 

References

  1. 1.
    Pietrobon D (2005) Migraine: new molecular mechanisms. Neuroscientist 11:373–386PubMedCrossRefGoogle Scholar
  2. 2.
    Ophoff RA, Terwindt GM, Vergouwe MN et al (1996) Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+channel gene CACNL1A4. Cell 87:543–552PubMedCrossRefGoogle Scholar
  3. 3.
    De Fusco M, Marconi R, Silvestri L, Atorino L, Rampoldi L, Morgante L et al (2003) Haploinsufficiency of ATP1A2 encoding the Na+/K+pump alpha2 subunit associated with familial hemiplegic migraine type 2. Nat Genet 33:192–196PubMedCrossRefGoogle Scholar
  4. 4.
    Dichgans M, Freilinger T, Eckstein G, Babini E, Lorenz-Depiereux B, Biskup S et al (2005) Mutation in the neuronal voltage-gated sodium channel SCN1A in familial hemiplegic migraine. Lancet 5(366):371–377CrossRefGoogle Scholar
  5. 5.
    Ferrari MD, Haan J (2002) The genetics of migraine: implication for treatment approaches. J Neural Transm Suppl 63:111–127PubMedGoogle Scholar
  6. 6.
    Pietrobon D (2007) Familial Hemiplegic migraine. Neurotherapeutics 4:274–284PubMedCrossRefGoogle Scholar
  7. 7.
    Bolay H, Reuter U, Dunn AK, Huang Z, Boas DA, Moskowitz MA (2002) Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model. Nat Med 8(136):142Google Scholar
  8. 8.
    Ambrosini A, Maertens de Noordhout A, Schoenen J (2001) Neuromuscular transmission in migraine: a single-fiber EMG study in clinical subgroups. Neurology 56:1038–1043PubMedGoogle Scholar
  9. 9.
    Plomp JJ, Vergouwe MN, Van den Maagdenberg AM, Ferrari MD, Frants RR, Molenaar PC (2000) Abnormal transmitter release at neuromuscular junctions of mice carrying the tottering alpha (1A) Ca (21) channel mutation. Brain 123:463–471PubMedCrossRefGoogle Scholar
  10. 10.
    Craig PJ, McAinsh AD, McCormack AL, Smith W, Beattie RE, Priestley JV (1998) Distribution of the voltage-dependent calcium channel alpha(1A) subunit throughout the mature rat brain and its relationship to neurotransmitter pathways. J Comp Neurol 397:251–267PubMedCrossRefGoogle Scholar
  11. 11.
    Terwindt GM, Ophoff RA, Haan J, Frants RR, Ferrari MD (1996) Familial hemiplegic migraine: a clinical comparison of families linked and unlinked to chromosome 19. Cephalalgia 16:153–155PubMedCrossRefGoogle Scholar
  12. 12.
    Sandor PS, Mascia A, Seidel L, de Pasqua V, Schoenen J (2001) Subclinical cerebellar impairment in the common types of migraine: a three-dimensional analysis of reaching movements. Ann Neurol 49:668–672PubMedCrossRefGoogle Scholar
  13. 13.
    Brighina F, Piazza A, Daniele O, Fierro B (2002) Modulation of visual cortical excitability in migraine with aura: effects of 1 Hz repetitive transcranial magnetic stimulation. Exp Brain Res 145:177–181PubMedCrossRefGoogle Scholar
  14. 14.
    Brighina F, Giglia G, Scalia S, Francolini M, Palermo A, Fierro B (2005) Facilitatory effects of 1 Hz rTMS in motor cortex of patients affected by migraine with aura. Exp Brain Res 161:34–38PubMedCrossRefGoogle Scholar
  15. 15.
    Siniatchkin M, Kroner-Herwig B, Kocabiyik E, Rothenberger A (2007) Intracortical inhibition and facilitation in migraine–a transcranial magnetic stimulation study. Headache 47:364–370PubMedGoogle Scholar
  16. 16.
    Dow RS (1974) Some novel concepts of cerebellar physiology. Mt Sinai J Med 41:103–119PubMedGoogle Scholar
  17. 17.
    Ugawa Y, Uesaka Y, Terao Y, Hanajima R, Kanazawa I (1995) Magnetic stimulation over the cerebellum in humans. Ann Neurol 37:703–713PubMedCrossRefGoogle Scholar
  18. 18.
    Pinto AD, Chen R (2001) Suppression of the motor cortex by magnetic stimulation of the cerebellum. Exp Brain Res 140:505–510PubMedCrossRefGoogle Scholar
  19. 19.
    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
  20. 20.
    Daskalakis ZJ, Christensen BK, Fitzgerald PB, Fountain SI, Chen R (2005) Reduced cerebellar inhibition in schizophrenia: a preliminary study. Am J Psychiatry 162:1203–1205PubMedCrossRefGoogle Scholar
  21. 21.
    Oldfield RC (1971) The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9:97–113PubMedCrossRefGoogle Scholar
  22. 22.
    Headache Classification Subcommittee of the International Headache Society (2004) The International Classification of Headache Disorders: 2nd edn. Cephalalgia 24(Suppl.1):9–160Google Scholar
  23. 23.
    41st World Medical Assembly (1990) Declaration of Helsinki: Recommendations guiding physicians in biomedical research, involving human subjects. Bull Pan Am Health Organ 24:606–609Google Scholar
  24. 24.
    Kaneko K, Kawai S, Fuchigami Y, Morita H, Ofuji A (1996) The effect of current direction induced by transcranial magnetic stimulation on the corticospinal excitability in human brain. Electroencephalogr Clin Neurophysiol 101:478–482PubMedCrossRefGoogle Scholar
  25. 25.
    Rothwell JC (1996) The use of paired pulse stimulation to investigate the intrinsic circuitry of human motor cortex. In: Nilsson J, Panizza M, Grandori F (eds) Advances in magnetic stimulation. Mathematical modeling and clinical applications. PI-ME, Pavia, pp 99–104Google Scholar
  26. 26.
    Brighina F, Daniele O, Piazza A, Giglia G, Fierro B (2006) Hemispheric cerebellar rTMS to treat drug-resistant epilepsy: case reports. Neurosci Lett 397:229–233PubMedCrossRefGoogle Scholar
  27. 27.
    Ugawa Y, Genba-Shimizu K, Rothwell JC, Iwata M, Kanazawa I (1994) Suppression of motor cortical excitability by electrical stimulation over the cerebellum in ataxia. Ann Neurol 36(1):90–96PubMedCrossRefGoogle Scholar
  28. 28.
    Mulleners WM, Chronicle EP, Palmer JE, Koehler PJ, Vredeveld JW (2001) Visual cortex excitability in migraine with and without aura. Headache 41:565–572PubMedCrossRefGoogle Scholar
  29. 29.
    Fierro B, Ricci R, Piazza A, Scalia S, Giglia G, Vitello G, Brighina F (2003) 1 Hz rTMS enhances extrastriate cortex activity in migraine: evidence of a reduced inhibition? Neurology 61:1446–1448PubMedGoogle Scholar
  30. 30.
    Aurora SK, al-Sayeed F, Welch KM (1999) The cortical silent period is shortened in migraine with aura. Cephalalgia 19:708–712PubMedCrossRefGoogle Scholar
  31. 31.
    Bramanti P, Grugno R, Vitetta A, Di Bella P, Muscara N, Nappi G (2005) Migraine with and without aura: electrophysiological and functional neuroimaging evidence. Funct Neurol 20:29–32PubMedGoogle Scholar
  32. 32.
    Currà A, Pierelli F, Coppola G, Barbanti P, Buzzi MG, Galeotti F et al (2007) Shortened cortical silent period in facial muscles of patients with migraine. Pain 132:124–131PubMedCrossRefGoogle Scholar
  33. 33.
    Van den Maagdenberg AM, Pietrobon D, Pizzorusso T, Kaja S, Broos LA, Cesetti T et al (2004) A Cacna1a knockin migraine mouse model with increased susceptibility to cortical spreading depression. Neuron 41(5):701–710, Mar 4PubMedCrossRefGoogle Scholar
  34. 34.
    Kruit MC, van Buchem MA, Hofman PA, Bakkers JT, Terwindt GM, Ferrari MD, Launer LJ (2004) Migraine as a risk factor for subclinical brain lesions. JAMA 291:427–434PubMedCrossRefGoogle Scholar
  35. 35.
    Kruit MC, Launer LJ, Ferrari MD, van Buchem MA (2005) Infarcts in the posterior circulation territory in migraine. The population-based MRI CAMERA study. Brain 128:2068–2077PubMedCrossRefGoogle Scholar
  36. 36.
    Kruit MC, Launer LJ, Ferrari MD, van Buchem MA (2006) Brain stem and cerebellar hyperintense lesions in migraine. Stroke 37:1109–1112PubMedCrossRefGoogle Scholar
  37. 37.
    Gerschlager W, Christensen LO, Bestmann S, Rothwell JC (2002) rTMS over the cerebellum can increase corticospinal excitability through a spinal mechanism involving activation of peripheral nerve fibres. Clin Neurophysiol 113:1435–440PubMedCrossRefGoogle Scholar
  38. 38.
    Werhahn KJ, Taylor J, Ridding M, Meyer BU, Rothwell JC (1996) Effect of transcranial magnetic stimulation over the cerebellum on the excitability of human motor cortex. Electroencephalogr Clin Neurophysiol 101:58–66PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Filippo Brighina
    • 1
  • Antonio Palermo
    • 1
  • Maristella L. Panetta
    • 1
  • Ornella Daniele
    • 1
  • Antonina Aloisio
    • 1
  • Giuseppe Cosentino
    • 1
  • Brigida Fierro
    • 1
  1. 1.Dipartimento Universitario di Neuroscienze ClinicheUniversity of PalermoPalermoItaly

Personalised recommendations