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

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

Functional connectivity studies in migraine: what have we learned?

Authors: Kirill Skorobogatykh, Willem Sebastiaan van Hoogstraten, Diana Degan, Anastasia Prischepa, Anastasya Savitskaya, Biondo Michela Ileen, Enrico Bentivegna, Iaroslav Skiba, Laura D’Acunto, Livia Ferri, Simona Sacco, Jakob Møller Hansen, Faisal Mohammad Amin, European Headache Federation School of Advanced Studies (EHF-SAS)

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

Login to get access

Abstract

Background

Resting-state functional connectivity (FC) MRI has widely been used to understand migraine pathophysiology and to identify an imaging marker of the disorder. Here, we review what we have learned from FC studies.

Methods

We performed a literature search on the PubMed website for original articles reporting data obtained from conventional resting-state FC recording in migraine patients compared with healthy controls or during and outside of migraine attacks in the same patients.

Results

We found 219 articles and included 28 in this review after screening for inclusion and exclusion criteria. Twenty-five studies compared migraine patients with healthy controls, whereas three studies investigated migraine patients during and outside of attacks. In the studies of interictal migraine more alterations of more than 20 FC networks (including amygdala, caudate nucleus, central executive, cerebellum, cuneus, dorsal attention network, default mode, executive control, fronto-parietal, hypothalamus, insula, neostriatum, nucleus accumbens, occipital lobe, periaqueductal grey, prefrontal cortex, salience, somatosensory cortex I, thalamus and visual) were reported. We found a poor level of reproducibility and no migraine specific pattern across these studies.

Conclusion

Based on the findings in the present review, it seems very difficult to extract knowledge of migraine pathophysiology or to identify a biomarker of migraine. There is an unmet need of guidelines for resting-state FC studies in migraine, which promote the use of homogenous terminology, public availability of protocol and the a priori hypothesis in line with for instance randomized clinical trial guidelines.
Appendix
Available only for authorised users
Literature
1.
go back to reference Mainero C, Boshyan J, Hadjikhani N (2011) Altered functional magnetic resonance imaging resting-state connectivity in periaqueductal gray networks in migraine. Ann Neurol 70:838–845CrossRef Mainero C, Boshyan J, Hadjikhani N (2011) Altered functional magnetic resonance imaging resting-state connectivity in periaqueductal gray networks in migraine. Ann Neurol 70:838–845CrossRef
2.
go back to reference Schwedt TJ, Chiang CC, Chong CD, Dodick DW (2015) Functional MRI of migraine. Lancet Neurol 14:81–91CrossRef Schwedt TJ, Chiang CC, Chong CD, Dodick DW (2015) Functional MRI of migraine. Lancet Neurol 14:81–91CrossRef
3.
go back to reference Yuan K, Qin W, Liu P, Zhao L, Yu D, Zhao L, Dong M, Liu J, Yang X, von Deneen KM, Liang F, Tian J (2012) Reduced fractional anisotropy of corpus callosum modulates inter-hemispheric resting state functional connectivity in migraine patients without aura. PLoS One 7:e45476CrossRef Yuan K, Qin W, Liu P, Zhao L, Yu D, Zhao L, Dong M, Liu J, Yang X, von Deneen KM, Liang F, Tian J (2012) Reduced fractional anisotropy of corpus callosum modulates inter-hemispheric resting state functional connectivity in migraine patients without aura. PLoS One 7:e45476CrossRef
4.
go back to reference Russo A, Tessitore A, Giordano A, Corbo D, Marcuccio L, De Stefano M, Salemi F, Conforti R, Esposito F, Tedeschi G (2012) Executive resting-state network connectivity in migraine without aura. Cephalalgia 32:1041–1048CrossRef Russo A, Tessitore A, Giordano A, Corbo D, Marcuccio L, De Stefano M, Salemi F, Conforti R, Esposito F, Tedeschi G (2012) Executive resting-state network connectivity in migraine without aura. Cephalalgia 32:1041–1048CrossRef
5.
go back to reference Jin C, Yuan K, Zhao L, Zhao L, Yu D, von Deneen KM, Zhang M, Qin W, Sun W, Tian J (2013) Structural and functional abnormalities in migraine patients without aura. NMR Biomed 26:58–64CrossRef Jin C, Yuan K, Zhao L, Zhao L, Yu D, von Deneen KM, Zhang M, Qin W, Sun W, Tian J (2013) Structural and functional abnormalities in migraine patients without aura. NMR Biomed 26:58–64CrossRef
6.
go back to reference Xue T, Yuan K, Zhao L, Yu D, Zhao L, Dong T, Cheng P, von Deneen KM, Qin W, Tian J (2012) Intrinsic brain network abnormalities in migraines without aura revealed in resting-state fMRI. PLoS One 7:e52927CrossRef Xue T, Yuan K, Zhao L, Yu D, Zhao L, Dong T, Cheng P, von Deneen KM, Qin W, Tian J (2012) Intrinsic brain network abnormalities in migraines without aura revealed in resting-state fMRI. PLoS One 7:e52927CrossRef
7.
go back to reference Xue T, Yuan K, Cheng P, Zhao L, Zhao L, Yu D, Dong T, von Deneen KM, Gong Q, Qin W, Tian J (2013) Alterations of regional spontaneous neuronal activity and corresponding brain circuit changes during resting state in migraine without aura. NMR Biomed 26:1051–1058CrossRef Xue T, Yuan K, Cheng P, Zhao L, Zhao L, Yu D, Dong T, von Deneen KM, Gong Q, Qin W, Tian J (2013) Alterations of regional spontaneous neuronal activity and corresponding brain circuit changes during resting state in migraine without aura. NMR Biomed 26:1051–1058CrossRef
8.
go back to reference Tessitore A, Russo A, Giordano A, Conte F, Corbo D, De Stefano M, Cirillo S, Cirillo M, Esposito F, Tedeschi G (2013) Disrupted default mode network connectivity in migraine without aura. J Headache Pain 14:89CrossRef Tessitore A, Russo A, Giordano A, Conte F, Corbo D, De Stefano M, Cirillo S, Cirillo M, Esposito F, Tedeschi G (2013) Disrupted default mode network connectivity in migraine without aura. J Headache Pain 14:89CrossRef
9.
go back to reference Schwedt TJ, Schlaggar BL, Mar S, Nolan T, Coalson RS, Nardos B, Benzinger T, Larson-Prior LJ (2013) Atypical resting-state functional connectivity of affective pain regions in chronic migraine. Headache 53:737–751CrossRef Schwedt TJ, Schlaggar BL, Mar S, Nolan T, Coalson RS, Nardos B, Benzinger T, Larson-Prior LJ (2013) Atypical resting-state functional connectivity of affective pain regions in chronic migraine. Headache 53:737–751CrossRef
10.
go back to reference Hadjikhani N, Ward N, Boshyan J, Napadow V, Maeda Y, Truini A, Caramia F, Tinelli E, Mainero C (2013) The missing link: enhanced functional connectivity between amygdala and visceroceptive cortex in migraine. Cephalalgia 33:1264–1268CrossRef Hadjikhani N, Ward N, Boshyan J, Napadow V, Maeda Y, Truini A, Caramia F, Tinelli E, Mainero C (2013) The missing link: enhanced functional connectivity between amygdala and visceroceptive cortex in migraine. Cephalalgia 33:1264–1268CrossRef
11.
go back to reference Yuan K, Zhao L, Cheng P, Yu D, Zhao L, Dong T, Xing L, Bi Y, Yang X, von Deneen KM, Liang F, Gong Q, Qin W, Tian J (2013) Altered structure and resting-state functional connectivity of the basal ganglia in migraine patients without aura. J Pain 14:836–844CrossRef Yuan K, Zhao L, Cheng P, Yu D, Zhao L, Dong T, Xing L, Bi Y, Yang X, von Deneen KM, Liang F, Gong Q, Qin W, Tian J (2013) Altered structure and resting-state functional connectivity of the basal ganglia in migraine patients without aura. J Pain 14:836–844CrossRef
12.
go back to reference Moulton EA, Becerra L, Johnson A, Burstein R, Borsook D (2014) Altered hypothalamic functional connectivity with autonomic circuits and the locus coeruleus in migraine. PLoS One 9:e95508CrossRef Moulton EA, Becerra L, Johnson A, Burstein R, Borsook D (2014) Altered hypothalamic functional connectivity with autonomic circuits and the locus coeruleus in migraine. PLoS One 9:e95508CrossRef
13.
go back to reference Tessitore A, Russo A, Conte F, Giordano A, De Stefano M, Lavorgna L, Corbo D, Caiazzo G, Esposito F, Tedeschi G (2015) Abnormal connectivity within executive resting-state network in migraine with aura. Headache 55:794–805CrossRef Tessitore A, Russo A, Conte F, Giordano A, De Stefano M, Lavorgna L, Corbo D, Caiazzo G, Esposito F, Tedeschi G (2015) Abnormal connectivity within executive resting-state network in migraine with aura. Headache 55:794–805CrossRef
14.
go back to reference Zhang J, Su J, Wang M, Zhao Y, Yao Q, Zhang Q, Lu H, Zhang H, Wang S, Li GF, Wu YL, Liu FD, Shi YH, Li J, Liu JR, Du X (2016) Increased default mode network connectivity and increased regional homogeneity in migraineurs without aura. J Headache Pain 17:98CrossRef Zhang J, Su J, Wang M, Zhao Y, Yao Q, Zhang Q, Lu H, Zhang H, Wang S, Li GF, Wu YL, Liu FD, Shi YH, Li J, Liu JR, Du X (2016) Increased default mode network connectivity and increased regional homogeneity in migraineurs without aura. J Headache Pain 17:98CrossRef
15.
go back to reference Coppola G, Di Renzo A, Tinelli E, Lepre C, Di Lorenzo C, Di Lorenzo G, Scapeccia M, Parisi V, Serrao M, Colonnese C, Schoenen J, Pierelli F (2016) Thalamo-cortical network activity between migraine attacks: insights from MRI-based microstructural and functional resting-state network correlation analysis. J Headache Pain 17:100CrossRef Coppola G, Di Renzo A, Tinelli E, Lepre C, Di Lorenzo C, Di Lorenzo G, Scapeccia M, Parisi V, Serrao M, Colonnese C, Schoenen J, Pierelli F (2016) Thalamo-cortical network activity between migraine attacks: insights from MRI-based microstructural and functional resting-state network correlation analysis. J Headache Pain 17:100CrossRef
16.
go back to reference Niddam DM, Lai KL, Fuh JL, Chuang CY, Chen WT, Wang SJ (2016) Reduced functional connectivity between salience and visual networks in migraine with aura. Cephalalgia 36:53–66CrossRef Niddam DM, Lai KL, Fuh JL, Chuang CY, Chen WT, Wang SJ (2016) Reduced functional connectivity between salience and visual networks in migraine with aura. Cephalalgia 36:53–66CrossRef
17.
go back to reference Tedeschi G, Russo A, Conte F, Corbo D, Caiazzo G, Giordano A, Conforti R, Esposito F, Tessitore A (2016) Increased interictal visual network connectivity in patients with migraine with aura. Cephalalgia 36:139–147CrossRef Tedeschi G, Russo A, Conte F, Corbo D, Caiazzo G, Giordano A, Conforti R, Esposito F, Tessitore A (2016) Increased interictal visual network connectivity in patients with migraine with aura. Cephalalgia 36:139–147CrossRef
18.
go back to reference Chen Z, Chen X, Liu M, Liu S, Shu S, Ma L, Yu S (2016) Altered functional connectivity of the marginal division in migraine: a resting-state fMRI study. J Headache Pain 17(1):89 Epub 2016 Sep 26. PubMed PMID: 27670428; PubMed Central PMCID: PMC5037100CrossRef Chen Z, Chen X, Liu M, Liu S, Shu S, Ma L, Yu S (2016) Altered functional connectivity of the marginal division in migraine: a resting-state fMRI study. J Headache Pain 17(1):89 Epub 2016 Sep 26. PubMed PMID: 27670428; PubMed Central PMCID: PMC5037100CrossRef
20.
go back to reference Androulakis XM, Krebs K, Peterlin BL, Zhang T, Maleki N, Sen S, Rorden C, Herath P (2017) Modulation of intrinsic resting-state fMRI networks in women with chronic migraine. Neurology 8(9):163–169CrossRef Androulakis XM, Krebs K, Peterlin BL, Zhang T, Maleki N, Sen S, Rorden C, Herath P (2017) Modulation of intrinsic resting-state fMRI networks in women with chronic migraine. Neurology 8(9):163–169CrossRef
21.
go back to reference Lo Buono V, Bonanno L, Corallo F, Pisani LR, Lo Presti R, Grugno R, Di Lorenzo G, Bramanti P, Marino S (2017) Functional connectivity and cognitive impairment in migraine with and without aura. J Headache Pain 18:72CrossRef Lo Buono V, Bonanno L, Corallo F, Pisani LR, Lo Presti R, Grugno R, Di Lorenzo G, Bramanti P, Marino S (2017) Functional connectivity and cognitive impairment in migraine with and without aura. J Headache Pain 18:72CrossRef
22.
go back to reference Hougaard A, Amin FM, Magon S, Sprenger T, Rostrup E, Ashina M (2015) No abnormalities of intrinsic brain connectivity in the interictal phase of migraine with aura. Eur J Neurol 22:702–e46CrossRef Hougaard A, Amin FM, Magon S, Sprenger T, Rostrup E, Ashina M (2015) No abnormalities of intrinsic brain connectivity in the interictal phase of migraine with aura. Eur J Neurol 22:702–e46CrossRef
23.
go back to reference Chen Z, Chen X, Liu M, Liu S, Ma L, Yu S (2017) Disrupted functional connectivity of periaqueductal gray subregions in episodic migraine. J Headache Pain 18:36CrossRef Chen Z, Chen X, Liu M, Liu S, Ma L, Yu S (2017) Disrupted functional connectivity of periaqueductal gray subregions in episodic migraine. J Headache Pain 18:36CrossRef
24.
go back to reference Chen Z, Chen X, Liu M, Dong Z, Ma L, Yu S (2017) Altered functional connectivity of amygdala underlying the neuromechanism of migraine pathogenesis. J Headache Pain 18:7CrossRef Chen Z, Chen X, Liu M, Dong Z, Ma L, Yu S (2017) Altered functional connectivity of amygdala underlying the neuromechanism of migraine pathogenesis. J Headache Pain 18:7CrossRef
25.
go back to reference Yu D, Yuan K, Luo L, Zhai J, Bi Y, Xue T, Ren X, Zhang M, Ren G, Lu X (2017) Abnormal functional integration across core brain networks in migraine without aura. Mol Pain 13:1744806917737461CrossRef Yu D, Yuan K, Luo L, Zhai J, Bi Y, Xue T, Ren X, Zhang M, Ren G, Lu X (2017) Abnormal functional integration across core brain networks in migraine without aura. Mol Pain 13:1744806917737461CrossRef
26.
go back to reference Zhang J, Su J, Wang M, Zhao Y, Zhang QT, Yao Q, Lu H, Zhang H, Li GF, Wu YL, Liu YS, Liu FD, Zhuang MT, Shi YH, Hou TY, Zhao R, Qiao Y, Li J, Liu JR, Du X (2017) The sensorimotor network dysfunction in migraineurs without aura: a resting-state fMRI study. J Neurol 264:654–663CrossRef Zhang J, Su J, Wang M, Zhao Y, Zhang QT, Yao Q, Lu H, Zhang H, Li GF, Wu YL, Liu YS, Liu FD, Zhuang MT, Shi YH, Hou TY, Zhao R, Qiao Y, Li J, Liu JR, Du X (2017) The sensorimotor network dysfunction in migraineurs without aura: a resting-state fMRI study. J Neurol 264:654–663CrossRef
27.
go back to reference Amin FM, Hougaard A, Magon S, Asghar MS, Ahmad NN, Rostrup E, Sprenger T, Ashina M (2016) Change in brain network connectivity during PACAP38-induced migraine attacks: a resting-state functional MRI study. Neurology 86:180–187CrossRef Amin FM, Hougaard A, Magon S, Asghar MS, Ahmad NN, Rostrup E, Sprenger T, Ashina M (2016) Change in brain network connectivity during PACAP38-induced migraine attacks: a resting-state functional MRI study. Neurology 86:180–187CrossRef
28.
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 3(8):2635–2642CrossRef 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 3(8):2635–2642CrossRef
29.
go back to reference Amin FM, Hougaard A, Magon S, Sprenger T, Wolfram F, Rostrup E, Ashina M (2018) Altered thalamic connectivity during spontaneous attacks of migraine without aura: a resting-state fMRI study. Cephalalgia 38:1237–1244CrossRef Amin FM, Hougaard A, Magon S, Sprenger T, Wolfram F, Rostrup E, Ashina M (2018) Altered thalamic connectivity during spontaneous attacks of migraine without aura: a resting-state fMRI study. Cephalalgia 38:1237–1244CrossRef
30.
go back to reference Wang T, Zhan W, Chen Q, Chen N, Zhang J, Liu Q, He L, Zhang J, Huang H, Gong Q (2016) Altered resting-state ascending/descending pathways associated with the posterior thalamus in migraine without aura. Neuroreport 27:257–263CrossRef Wang T, Zhan W, Chen Q, Chen N, Zhang J, Liu Q, He L, Zhang J, Huang H, Gong Q (2016) Altered resting-state ascending/descending pathways associated with the posterior thalamus in migraine without aura. Neuroreport 27:257–263CrossRef
31.
go back to reference Ning Y, Zheng R, Li K, Zhang Y, Lyu D, Jia H, Ren Y, Zou Y (2018) The altered Granger causality connection among pain-related brain networks in migraine. Medicine (Baltimore) 97:e0102CrossRef Ning Y, Zheng R, Li K, Zhang Y, Lyu D, Jia H, Ren Y, Zou Y (2018) The altered Granger causality connection among pain-related brain networks in migraine. Medicine (Baltimore) 97:e0102CrossRef
32.
go back to reference Wang T, Chen N, Zhan W, Liu J, Zhang J, Liu Q, Huang H, He L, Zhang J, Gong Q (2015) Altered effective connectivity of posterior thalamus in migraine with cutaneous allodynia: a resting-state fMRI study with granger causality analysis. J Headache Pain 17:17CrossRef Wang T, Chen N, Zhan W, Liu J, Zhang J, Liu Q, Huang H, He L, Zhang J, Gong Q (2015) Altered effective connectivity of posterior thalamus in migraine with cutaneous allodynia: a resting-state fMRI study with granger causality analysis. J Headache Pain 17:17CrossRef
33.
go back to reference Napadow V, Harris RE (2014) What has functional connectivity and chemical neuroimaging in fibromyalgia taught us about the mechanisms and management of ‘centralized’ pain? Arthritis Res Ther 16:425CrossRef Napadow V, Harris RE (2014) What has functional connectivity and chemical neuroimaging in fibromyalgia taught us about the mechanisms and management of ‘centralized’ pain? Arthritis Res Ther 16:425CrossRef
34.
go back to reference Wolters AF, van de Weijer SCF, Leentjens AFG, Duits AA, Jacobs HIL, Kuijf ML (2018) Resting-state fMRI in Parkinson’s disease patients with cognitive impairment: a meta-analysis. Parkinsonism Relat Disord S1353-8020(18):30550–30559 Wolters AF, van de Weijer SCF, Leentjens AFG, Duits AA, Jacobs HIL, Kuijf ML (2018) Resting-state fMRI in Parkinson’s disease patients with cognitive impairment: a meta-analysis. Parkinsonism Relat Disord S1353-8020(18):30550–30559
35.
go back to reference Filippi M, Sarasso E, Agosta F (2019) Resting-state functional MRI in Parkinsonian syndromes. Mov Disord Clin Pract 6:104–117CrossRef Filippi M, Sarasso E, Agosta F (2019) Resting-state functional MRI in Parkinsonian syndromes. Mov Disord Clin Pract 6:104–117CrossRef
36.
go back to reference Heine L, Soddu A, Gömez F, Vanhaudenhuyse A, Tshibanda L, Thonnard M, Charland-Verville V, Kirsch M, Laureys S, Demertzi A (2012) Resting state networks and consciousness: alterations of multiple resting state networks connectivity in physiological, pharmacological, and pathological consciousness states. Front Psychol 3:295CrossRef Heine L, Soddu A, Gömez F, Vanhaudenhuyse A, Tshibanda L, Thonnard M, Charland-Verville V, Kirsch M, Laureys S, Demertzi A (2012) Resting state networks and consciousness: alterations of multiple resting state networks connectivity in physiological, pharmacological, and pathological consciousness states. Front Psychol 3:295CrossRef
37.
go back to reference Mikdashi JA (2016) Altered functional neuronal activity in neuropsychiatric lupus: a systematic review of the fMRI investigations. Semin Arthritis Rheum 45:455–462CrossRef Mikdashi JA (2016) Altered functional neuronal activity in neuropsychiatric lupus: a systematic review of the fMRI investigations. Semin Arthritis Rheum 45:455–462CrossRef
38.
go back to reference Kharabian Masouleh S, Herzig S, Klose L, Roggenhofer E, Tenckhoff H, Kaiser T, Thöne-Otto A, Wiese M, Berg T, Schroeter ML, Margulies DS, Villringer A (2017) Functional connectivity alterations in patients with chronic hepatitis C virus infection: a multimodal MRI study. J Viral Hepat 24:216–225CrossRef Kharabian Masouleh S, Herzig S, Klose L, Roggenhofer E, Tenckhoff H, Kaiser T, Thöne-Otto A, Wiese M, Berg T, Schroeter ML, Margulies DS, Villringer A (2017) Functional connectivity alterations in patients with chronic hepatitis C virus infection: a multimodal MRI study. J Viral Hepat 24:216–225CrossRef
Metadata
Title
Functional connectivity studies in migraine: what have we learned?
Authors
Kirill Skorobogatykh
Willem Sebastiaan van Hoogstraten
Diana Degan
Anastasia Prischepa
Anastasya Savitskaya
Biondo Michela Ileen
Enrico Bentivegna
Iaroslav Skiba
Laura D’Acunto
Livia Ferri
Simona Sacco
Jakob Møller Hansen
Faisal Mohammad Amin
European Headache Federation School of Advanced Studies (EHF-SAS)
Publication date
01-12-2019
Publisher
Springer Milan
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/s10194-019-1047-3

Other articles of this Issue 1/2019

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