Skip to main content
Top
Published in: The Journal of Headache and Pain 1/2019

Open Access 01-12-2019 | Migraine | Research article

Advanced visual network and cerebellar hyperresponsiveness to trigeminal nociception in migraine with aura

Authors: Antonio Russo, Alessandro Tessitore, Marcello Silvestro, Federica Di Nardo, Francesca Trojsi, Teresa Del Santo, Rosa De Micco, Fabrizio Esposito, Gioacchino Tedeschi

Published in: The Journal of Headache and Pain | Issue 1/2019

Login to get access

Abstract

Background

Despite the growing body of advanced studies investigating the neuronal correlates of pain processing in patients with migraine without aura (MwoA), only few similar studies have been conducted in patients with migraine with aura (MwA). Therefore, we aimed to explore the functional brain response to trigeminal noxious heat stimulation in patients with MwA.

Methods

Seventeen patients with MwA and 15 age- and sex-matched healthy controls (HC) underwent whole-brain blood oxygen level–dependent (BOLD) fMRI during trigeminal noxious heat stimulation. To examine the specificity of any observed differences between patients with MwA and HC, the functional response of neural pathways to trigeminal noxious heat stimulation in patients with MwA was compared with 18 patients with MwoA. Secondary analyses investigated the correlations between BOLD signal changes and clinical parameters of migraine severity.

Results

We observed a robust cortical and subcortical pattern of BOLD response to trigeminal noxious heat stimulation across all participants. Patients with MwA showed a significantly increased activity in higher cortical areas known to be part of a distributed network involved in advanced visual processing, including lingual gyrus, inferior parietal lobule, inferior frontal gyrus and medial frontal gyrus. Moreover, a significantly greater cerebellar activation was observed in patients with MwA when compared with both patients with MwA and HC. Interestingly, no correlations were found between migraine severity parameters and magnitude of BOLD response in patients with MwA.

Conclusion

Our findings, characterized by abnormal visual pathway response to trigeminal noxious heat stimulation, support the role of a functional integration between visual and trigeminal pain networks in the pathophysiological mechanisms underlying migraine with aura. Moreover, they expand the concept of “neurolimbic-pain network” as a model of MwoA including both limbic dysfunction and cortical dys-excitability. Indeed, we suggest a model of “neurolimbic-visual-pain network” in MwA patients, characterized by dysfunctional correlations between pain-modulating circuits not only with the cortical limbic areas but with advanced visual areas as well. Furthermore, the abnormal cerebellar response to trigeminal noxious heat stimulation may suggest a dysfunctional cerebellar inhibitory control on thalamic sensory gating, impinging on the advanced visual processing cortical areas in patients with MwA.
Appendix
Available only for authorised users
Literature
1.
go back to reference Noseda R, Burstein R (2013) Migraine pathophysiology: anatomy of the trigeminovascular pathway and associated neurological symptoms, cortical spreading depression, sensitization, and modulation of pain. Pain. 154(Suppl. 1:S44–S53CrossRefPubMed Noseda R, Burstein R (2013) Migraine pathophysiology: anatomy of the trigeminovascular pathway and associated neurological symptoms, cortical spreading depression, sensitization, and modulation of pain. Pain. 154(Suppl. 1:S44–S53CrossRefPubMed
2.
go back to reference Moskowitz MA, Nozaki K, Kraig RP (1993) Neocortical spreading depression provokes the expression of c-fos protein-like immunoreactivity within trigeminal nucleus caudalis via trigeminovascular mechanisms. J Neurosci 13:1167–1177CrossRefPubMedPubMedCentral Moskowitz MA, Nozaki K, Kraig RP (1993) Neocortical spreading depression provokes the expression of c-fos protein-like immunoreactivity within trigeminal nucleus caudalis via trigeminovascular mechanisms. J Neurosci 13:1167–1177CrossRefPubMedPubMedCentral
3.
go back to reference Tepe N, Filiz A, Dilekoz E, Akcali D, Sara Y, Charles A et al (2015) The thalamic reticular nucleus is activated by cortical spreading depression in freely moving rats: prevention by acute valproate administration. Eur J Neurosci 41(1):120–128CrossRefPubMed Tepe N, Filiz A, Dilekoz E, Akcali D, Sara Y, Charles A et al (2015) The thalamic reticular nucleus is activated by cortical spreading depression in freely moving rats: prevention by acute valproate administration. Eur J Neurosci 41(1):120–128CrossRefPubMed
4.
go back to reference Demarquay G, Mauguière F (2016) Central nervous system underpinnings of sensory hypersensitivity in migraine: insights from neuroimaging and electrophysiological studies. Headache. 56(9):1418–1438CrossRefPubMed Demarquay G, Mauguière F (2016) Central nervous system underpinnings of sensory hypersensitivity in migraine: insights from neuroimaging and electrophysiological studies. Headache. 56(9):1418–1438CrossRefPubMed
5.
go back to reference Headache Classification Committee of the International Headache Society (2013) The international classification of headache disorders, 3rd edition (beta version). Cephalalgia 33:629–808CrossRef Headache Classification Committee of the International Headache Society (2013) The international classification of headache disorders, 3rd edition (beta version). Cephalalgia 33:629–808CrossRef
6.
go back to reference Russo A, Tessitore A, Esposito F, Marcuccio L, Giordano A, Conforti R et al (2012) Pain processing in patients with migraine: an event-related fMRI study during trigeminal nociceptive stimulation. J Neurol 259(9):1903–1912CrossRefPubMed Russo A, Tessitore A, Esposito F, Marcuccio L, Giordano A, Conforti R et al (2012) Pain processing in patients with migraine: an event-related fMRI study during trigeminal nociceptive stimulation. J Neurol 259(9):1903–1912CrossRefPubMed
7.
go back to reference Russo A, Esposito F, Conte F, Fratello M, Caiazzo G, Marcuccio L et al (2017) Functional interictal changes of pain processing in migraine with ictal cutaneous allodynia. Cephalalgia. 37(4):305–314CrossRefPubMed Russo A, Esposito F, Conte F, Fratello M, Caiazzo G, Marcuccio L et al (2017) Functional interictal changes of pain processing in migraine with ictal cutaneous allodynia. Cephalalgia. 37(4):305–314CrossRefPubMed
8.
go back to reference Friston KJ, Holmes AP, Poline JB, Grasby PJ, Williams SC, Frackowiak RS et al (1995) Analysis of fMRI time-series revisited. Neuroimage. 2(1):45–53CrossRefPubMed Friston KJ, Holmes AP, Poline JB, Grasby PJ, Williams SC, Frackowiak RS et al (1995) Analysis of fMRI time-series revisited. Neuroimage. 2(1):45–53CrossRefPubMed
9.
go back to reference Schwedt TJ, Chiang CC, Chong CD, Dodick DW (2015) Functional MRI of migraine. Lancet Neurol 14(1):81–91CrossRefPubMed Schwedt TJ, Chiang CC, Chong CD, Dodick DW (2015) Functional MRI of migraine. Lancet Neurol 14(1):81–91CrossRefPubMed
10.
go back to reference Hougaard A, Amin FM, Hoffmann MB, Rostrup E, Larsson HB, Asghar MS et al (2014) Interhemispheric differences of fMRI responses to visual stimuli in patients with side-fixed migraine aura. Hum Brain Mapp 35(6):2714–2723CrossRefPubMed Hougaard A, Amin FM, Hoffmann MB, Rostrup E, Larsson HB, Asghar MS et al (2014) Interhemispheric differences of fMRI responses to visual stimuli in patients with side-fixed migraine aura. Hum Brain Mapp 35(6):2714–2723CrossRefPubMed
11.
go back to reference Van Essen DC, Gallant JL (1994) Neural mechanisms of form and motion processing in the primate visual system. Neuron. 13:1–10CrossRefPubMed Van Essen DC, Gallant JL (1994) Neural mechanisms of form and motion processing in the primate visual system. Neuron. 13:1–10CrossRefPubMed
12.
go back to reference Seeck M, Schomer D, Mainwaring N, Ives J, Dubuisson D, Blume H et al (1995) Selectively distributed processing of visual object recognition in the temporal and frontal lobes of the human brain. Ann Neurol 37(4):538–545CrossRefPubMed Seeck M, Schomer D, Mainwaring N, Ives J, Dubuisson D, Blume H et al (1995) Selectively distributed processing of visual object recognition in the temporal and frontal lobes of the human brain. Ann Neurol 37(4):538–545CrossRefPubMed
13.
go back to reference Rizzolatti G, Matelli M (2003) Two different streams form the dorsal visual system: Anatomy and functions. Exp Brain Res 153:146–157CrossRefPubMed Rizzolatti G, Matelli M (2003) Two different streams form the dorsal visual system: Anatomy and functions. Exp Brain Res 153:146–157CrossRefPubMed
14.
go back to reference Magis D, Vigano A, Sava S et al (2013) Pearls and pitfalls: electrophysiology for primary headaches. Cephalalgia. 33:526CrossRefPubMed Magis D, Vigano A, Sava S et al (2013) Pearls and pitfalls: electrophysiology for primary headaches. Cephalalgia. 33:526CrossRefPubMed
15.
go back to reference Datta R, Aguirre GK, Hu S, Detre JA, Cucchiara B (2013) Interictal cortical hyperresponsiveness in migraine is directly related to the presence of aura. Cephalalgia 33(6):365–374CrossRefPubMedPubMedCentral Datta R, Aguirre GK, Hu S, Detre JA, Cucchiara B (2013) Interictal cortical hyperresponsiveness in migraine is directly related to the presence of aura. Cephalalgia 33(6):365–374CrossRefPubMedPubMedCentral
16.
go back to reference Tedeschi G, Russo A, Conte F, Corbo D, Caiazzo G, Giordano A et al (2016) Increased interictal visual network connectivity in patients with migraine with aura. Cephalalgia. 36(2):139–147CrossRefPubMed Tedeschi G, Russo A, Conte F, Corbo D, Caiazzo G, Giordano A et al (2016) Increased interictal visual network connectivity in patients with migraine with aura. Cephalalgia. 36(2):139–147CrossRefPubMed
17.
go back to reference Bridge H, Stagg CJ, Near J, Lau CI, Zisner A, Cader MZ (2015) Altered neurochemical coupling in the occipital cortex in migraine with visual aura. Cephalalgia. 35(11):1025–1030CrossRefPubMed Bridge H, Stagg CJ, Near J, Lau CI, Zisner A, Cader MZ (2015) Altered neurochemical coupling in the occipital cortex in migraine with visual aura. Cephalalgia. 35(11):1025–1030CrossRefPubMed
18.
go back to reference Hougaard A, Amin FM, Christensen CE, Younis S, Wolfram F, Cramer SP et al (2017) Increased brainstem perfusion, but no blood-brain barrier disruption, during attacks of migraine with aura. Brain 140(6):1633–1642CrossRefPubMed Hougaard A, Amin FM, Christensen CE, Younis S, Wolfram F, Cramer SP et al (2017) Increased brainstem perfusion, but no blood-brain barrier disruption, during attacks of migraine with aura. Brain 140(6):1633–1642CrossRefPubMed
19.
go back to reference Hougaard A, Amin FM, Larsson HB, Rostrup E, Ashina M (2017) Increased intrinsic brain connectivity between pons and somatosensory cortex during attacks of migraine with aura. Hum Brain Mapp 38(5):2635–2642CrossRefPubMed Hougaard A, Amin FM, Larsson HB, Rostrup E, Ashina M (2017) Increased intrinsic brain connectivity between pons and somatosensory cortex during attacks of migraine with aura. Hum Brain Mapp 38(5):2635–2642CrossRefPubMed
20.
go back to reference Afridi S, Kaube H, Goadsby PJ (2005) Occipital activation in glyceryl trinitrate induced migraine with visual aura. J Neurol Neurosurg Psychiatry 76(8):1158–1160CrossRefPubMedPubMedCentral Afridi S, Kaube H, Goadsby PJ (2005) Occipital activation in glyceryl trinitrate induced migraine with visual aura. J Neurol Neurosurg Psychiatry 76(8):1158–1160CrossRefPubMedPubMedCentral
21.
go back to reference Boulloche N, Denuelle M, Payoux P, Fabre N, Trotter Y, Géraud G (2010) Photophobia in migraine: an interictal PET study of cortical hyperexcitability and its modulation by pain. J Neurol Neurosurg Psychiatry 81(9):978–984CrossRefPubMed Boulloche N, Denuelle M, Payoux P, Fabre N, Trotter Y, Géraud G (2010) Photophobia in migraine: an interictal PET study of cortical hyperexcitability and its modulation by pain. J Neurol Neurosurg Psychiatry 81(9):978–984CrossRefPubMed
22.
go back to reference Walker R, Husain M, Hodgson TL, Harrison J (1998) Saccadic eye movement and working memory deficits following damage to human prefrontal cortex. Neuropsychologia. 36:1141–1159CrossRefPubMed Walker R, Husain M, Hodgson TL, Harrison J (1998) Saccadic eye movement and working memory deficits following damage to human prefrontal cortex. Neuropsychologia. 36:1141–1159CrossRefPubMed
23.
go back to reference Petit L, Haxby JV (1999) Functional anatomy of pursuit eye movements in humans as revealed by fMRI. J Neurophysiol 82(1):463–471CrossRefPubMed Petit L, Haxby JV (1999) Functional anatomy of pursuit eye movements in humans as revealed by fMRI. J Neurophysiol 82(1):463–471CrossRefPubMed
24.
go back to reference Kim JH, Suh SI, Seol HY, Oh K, Seo WK, Yu SW et al (2008) Regional grey matter changes in patients with migraine: a voxel-based morphometry study. Cephalalgia. 28(6):598–604CrossRefPubMed Kim JH, Suh SI, Seol HY, Oh K, Seo WK, Yu SW et al (2008) Regional grey matter changes in patients with migraine: a voxel-based morphometry study. Cephalalgia. 28(6):598–604CrossRefPubMed
25.
go back to reference Arkink EB, Bleeker EJ, Schmitz N, Schoonman GG, Wu O, Ferrari MD et al (2012) Cerebral perfusion changes in migraineurs: a voxelwise comparison of interictal dynamic susceptibility contrast MRI measurements. Cephalalgia. 32(4):279–288CrossRefPubMedPubMedCentral Arkink EB, Bleeker EJ, Schmitz N, Schoonman GG, Wu O, Ferrari MD et al (2012) Cerebral perfusion changes in migraineurs: a voxelwise comparison of interictal dynamic susceptibility contrast MRI measurements. Cephalalgia. 32(4):279–288CrossRefPubMedPubMedCentral
26.
27.
go back to reference Edvinsson L, Eftekhari S, Salvatore CA, Warfvinge K (2011) Cerebellar distribution of calcitonin gene-related peptide (CGRP) and its receptor components calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) in rat. Mol Cell Neurosci 46(1):333–339CrossRefPubMed Edvinsson L, Eftekhari S, Salvatore CA, Warfvinge K (2011) Cerebellar distribution of calcitonin gene-related peptide (CGRP) and its receptor components calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) in rat. Mol Cell Neurosci 46(1):333–339CrossRefPubMed
28.
go back to reference Ruscheweyh R, Kühnel M, Filippopulos F, Blum B, Eggert T, Straube A (2014) Altered experimental pain perception after cerebellar infarction. Pain. 155(7):1303–1312CrossRefPubMed Ruscheweyh R, Kühnel M, Filippopulos F, Blum B, Eggert T, Straube A (2014) Altered experimental pain perception after cerebellar infarction. Pain. 155(7):1303–1312CrossRefPubMed
29.
go back to reference Helmchen C, Mohr C, Erdmann C, Binkofski F (2004) Cerebellar neural responses related to actively and passively applied noxious thermal stimulation in human subjects: a parametric fMRI study. Neurosci Lett 361(1–3):237–240CrossRefPubMed Helmchen C, Mohr C, Erdmann C, Binkofski F (2004) Cerebellar neural responses related to actively and passively applied noxious thermal stimulation in human subjects: a parametric fMRI study. Neurosci Lett 361(1–3):237–240CrossRefPubMed
30.
go back to reference Kros L, Angueyra Aristizábal CA, Khodakhah K (2018) Cerebellar involvement in migraine. Cephalalgia. 1:333102417752120 Kros L, Angueyra Aristizábal CA, Khodakhah K (2018) Cerebellar involvement in migraine. Cephalalgia. 1:333102417752120
31.
go back to reference Mehnert J, May A (2017) Functional and structural alterations in the migraine cerebellum. J Cereb Blood Flow Metab 1:271678X17722109 Mehnert J, May A (2017) Functional and structural alterations in the migraine cerebellum. J Cereb Blood Flow Metab 1:271678X17722109
32.
go back to reference Brighina F, Palermo A, Panetta ML, Daniele O, Aloisio A, Cosentino G et al (2009) Reduced cerebellar inhibition in migraine with aura: a TMS study. Cerebellum. 8(3):260–266CrossRefPubMed Brighina F, Palermo A, Panetta ML, Daniele O, Aloisio A, Cosentino G et al (2009) Reduced cerebellar inhibition in migraine with aura: a TMS study. Cerebellum. 8(3):260–266CrossRefPubMed
33.
go back to reference Mehnert J, Schulte L, Timmann D, May A (2017) Activity and connectivity of the cerebellum in trigeminal nociception. Neuroimage. 15(150):112–118CrossRef Mehnert J, Schulte L, Timmann D, May A (2017) Activity and connectivity of the cerebellum in trigeminal nociception. Neuroimage. 15(150):112–118CrossRef
34.
go back to reference Baier B, Dieterich M (2011) Incidence and anatomy of gaze-evoked nystagmus in patients with cerebellar lesions. Neurology 76(4):361–365CrossRefPubMed Baier B, Dieterich M (2011) Incidence and anatomy of gaze-evoked nystagmus in patients with cerebellar lesions. Neurology 76(4):361–365CrossRefPubMed
35.
go back to reference Russo A, Tessitore A, Bruno A, Siciliano M, Marcuccio L, Silvestro M et al (2018) Migraine does not affect pain intensity perception: a cross-sectional study. Pain Med 19(8):1657–1666CrossRefPubMed Russo A, Tessitore A, Bruno A, Siciliano M, Marcuccio L, Silvestro M et al (2018) Migraine does not affect pain intensity perception: a cross-sectional study. Pain Med 19(8):1657–1666CrossRefPubMed
36.
go back to reference Maizels M, Aurora S, Heinricher M (2012) Beyond neurovascular: migraine as a dysfunctional neurolimbic pain network. Headache. 52(10):1553–1565CrossRefPubMed Maizels M, Aurora S, Heinricher M (2012) Beyond neurovascular: migraine as a dysfunctional neurolimbic pain network. Headache. 52(10):1553–1565CrossRefPubMed
Metadata
Title
Advanced visual network and cerebellar hyperresponsiveness to trigeminal nociception in migraine with aura
Authors
Antonio Russo
Alessandro Tessitore
Marcello Silvestro
Federica Di Nardo
Francesca Trojsi
Teresa Del Santo
Rosa De Micco
Fabrizio Esposito
Gioacchino Tedeschi
Publication date
01-12-2019
Publisher
Springer Milan
Keywords
Migraine
Aura
Published in
The Journal of Headache and Pain / Issue 1/2019
Print ISSN: 1129-2369
Electronic ISSN: 1129-2377
DOI
https://doi.org/10.1186/s10194-019-1002-3

Other articles of this Issue 1/2019

The Journal of Headache and Pain 1/2019 Go to the issue