Skip to main content

Advertisement

SpringerLink
Log in

Reduced Cerebellar Inhibition in Migraine with Aura: A TMS Study

  • Published:
The Cerebellum Aims and scope Submit manuscript

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.

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.

Similar content being viewed by others

References

  1. Pietrobon D (2005) Migraine: new molecular mechanisms. Neuroscientist 11:373–386

    Article  PubMed  CAS  Google Scholar 

  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 87:543–552

    Article  PubMed  CAS  Google Scholar 

  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 33:192–196

    Article  PubMed  Google Scholar 

  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):371–377

    Article  Google Scholar 

  5. Ferrari MD, Haan J (2002) The genetics of migraine: implication for treatment approaches. J Neural Transm Suppl 63:111–127

    PubMed  CAS  Google Scholar 

  6. Pietrobon D (2007) Familial Hemiplegic migraine. Neurotherapeutics 4:274–284

    Article  PubMed  CAS  Google Scholar 

  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):142

    Google Scholar 

  8. Ambrosini A, Maertens de Noordhout A, Schoenen J (2001) Neuromuscular transmission in migraine: a single-fiber EMG study in clinical subgroups. Neurology 56:1038–1043

    PubMed  CAS  Google Scholar 

  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 123:463–471

    Article  PubMed  Google Scholar 

  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 397:251–267

    Article  PubMed  CAS  Google Scholar 

  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 16:153–155

    Article  PubMed  CAS  Google Scholar 

  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 49:668–672

    Article  PubMed  CAS  Google Scholar 

  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 145:177–181

    Article  PubMed  Google Scholar 

  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 161:34–38

    Article  PubMed  Google Scholar 

  15. Siniatchkin M, Kroner-Herwig B, Kocabiyik E, Rothenberger A (2007) Intracortical inhibition and facilitation in migraine–a transcranial magnetic stimulation study. Headache 47:364–370

    PubMed  Google Scholar 

  16. Dow RS (1974) Some novel concepts of cerebellar physiology. Mt Sinai J Med 41:103–119

    PubMed  CAS  Google Scholar 

  17. Ugawa Y, Uesaka Y, Terao Y, Hanajima R, Kanazawa I (1995) Magnetic stimulation over the cerebellum in humans. Ann Neurol 37:703–713

    Article  PubMed  CAS  Google Scholar 

  18. Pinto AD, Chen R (2001) Suppression of the motor cortex by magnetic stimulation of the cerebellum. Exp Brain Res 140:505–510

    Article  PubMed  CAS  Google Scholar 

  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 557:689–700

    Article  PubMed  CAS  Google Scholar 

  20. Daskalakis ZJ, Christensen BK, Fitzgerald PB, Fountain SI, Chen R (2005) Reduced cerebellar inhibition in schizophrenia: a preliminary study. Am J Psychiatry 162:1203–1205

    Article  PubMed  Google Scholar 

  21. Oldfield RC (1971) The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9:97–113

    Article  PubMed  CAS  Google Scholar 

  22. Headache Classification Subcommittee of the International Headache Society (2004) The International Classification of Headache Disorders: 2nd edn. Cephalalgia 24(Suppl.1):9–160

    Google Scholar 

  23. 41st World Medical Assembly (1990) Declaration of Helsinki: Recommendations guiding physicians in biomedical research, involving human subjects. Bull Pan Am Health Organ 24:606–609

    Google Scholar 

  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 101:478–482

    Article  PubMed  CAS  Google Scholar 

  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 99–104

    Google Scholar 

  26. Brighina F, Daniele O, Piazza A, Giglia G, Fierro B (2006) Hemispheric cerebellar rTMS to treat drug-resistant epilepsy: case reports. Neurosci Lett 397:229–233

    Article  PubMed  CAS  Google Scholar 

  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):90–96

    Article  PubMed  CAS  Google Scholar 

  28. Mulleners WM, Chronicle EP, Palmer JE, Koehler PJ, Vredeveld JW (2001) Visual cortex excitability in migraine with and without aura. Headache 41:565–572

    Article  PubMed  CAS  Google Scholar 

  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 61:1446–1448

    PubMed  CAS  Google Scholar 

  30. Aurora SK, al-Sayeed F, Welch KM (1999) The cortical silent period is shortened in migraine with aura. Cephalalgia 19:708–712

    Article  PubMed  CAS  Google Scholar 

  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 20:29–32

    PubMed  Google Scholar 

  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 132:124–131

    Article  PubMed  Google Scholar 

  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 4

    Article  PubMed  Google Scholar 

  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 291:427–434

    Article  PubMed  CAS  Google Scholar 

  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 128:2068–2077

    Article  PubMed  Google Scholar 

  36. Kruit MC, Launer LJ, Ferrari MD, van Buchem MA (2006) Brain stem and cerebellar hyperintense lesions in migraine. Stroke 37:1109–1112

    Article  PubMed  Google Scholar 

  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 113:1435–440

    Article  PubMed  CAS  Google Scholar 

  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 101:58–66

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dipartimento Universitario di Neuroscienze Cliniche, University of Palermo, Via G. La Loggia, 1, 90129, Palermo, Italy

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

Authors
  1. Filippo Brighina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Antonio Palermo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maristella L. Panetta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ornella Daniele
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Antonina Aloisio
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Giuseppe Cosentino
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Brigida Fierro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Brigida Fierro.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brighina, F., Palermo, A., Panetta, M.L. et al. Reduced Cerebellar Inhibition in Migraine with Aura: A TMS Study. Cerebellum 8, 260–266 (2009). https://doi.org/10.1007/s12311-008-0090-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12311-008-0090-4

Keywords

Search

Navigation