BACKGROUND: Migraine is one of the most severe primary headache disorders. The nature of the headache and the associated symptoms during the attack suggest underlying functional alterations in the brain. In this study, we examined amplitude, the resting state fMRI fluctuation in migraineurs with and without aura (MWA, MWoA respectively) and healthy controls. METHODS: Resting state functional MRI images and T1 high-resolution images were acquired from all participants. For data analysis we compared the groups (MWA-Control, MWA-MWoA, MWoA-Control). The resting state networks were identified by MELODIC. The mean time courses of the networks were identified for each participant for all networks. The time-courses were decomposed into five frequency bands by discrete wavelet decomposition. The amplitude of the frequency-specific activity was compared between groups. Furthermore, the preprocessed resting state images were decomposed by wavelet analysis into five specific frequency bands voxel-wise. The voxel-wise amplitudes were compared between groups by non-parametric permutation test. RESULTS: In the MWA-Control comparison the discrete wavelet decomposition found alterations in the lateral visual network. Higher activity was measured in the MWA group in the highest frequency band (0.16-0.08 Hz). In case of the MWA-MWoA comparison all networks showed higher activity in the 0.08-0.04 Hz frequency range in MWA, and the lateral visual network in in higher frequencies. In MWoA-Control comparison only the default mode network revealed decreased activity in MWoA group in the 0.08-0.04 Hz band. The voxel-wise frequency specific analysis of the amplitudes found higher amplitudes in MWA as compared to MWoA in the in fronto-parietal regions, anterior cingulate cortex and cerebellum. DISCUSSION: The amplitude of the resting state fMRI activity fluctuation is higher in MWA than in MWoA. These results are in concordance with former studies, which found cortical hyperexcitability in MWA.

Department of Neurology Neuroimaging Research Group Albert Szent Györgyi Clinical Center University of Szeged Semmelweis u 6 H 6725 Szeged Hungary

International Clinical Research Center St Anne's University Hospital Brno Brno Czech Republic

MTA SZTE Neuroscience Research Group Szeged Hungary

Zobrazit více v PubMed

Lipton RB, Bigal ME, Steiner TJ, Silberstein SD, Olesen J. Classification of primary headaches. Neurology. 2004;63:427–435. doi: 10.1212/01.WNL.0000133301.66364.9B. PubMed DOI

Headache Classification Committee of the International Headache The international classification of headache disorders, 3rd edition (beta version) Cephalalgia. 2013;33:629–808. doi: 10.1177/0333102413485658. PubMed DOI

Manzoni GC, Torelli P. Migraine with and without aura: a single entity? Neurol sci. 2008;29(Suppl 1):S40–43. doi: 10.1007/s10072-008-0884-7. PubMed DOI

Ranson R, Igarashi H, MacGregor EA, Wilkinson M. The similarities and differences of migraine with aura and migraine without aura: a preliminary study. Cephalalgia. 1991;11:189–192. doi: 10.1046/j.1468-2982.1991.1104189.x. PubMed DOI

Hadjikhani N, Sanchez Del Rio M, Wu O, Schwartz D, Bakker D, Fischl B, Kwong KK, Cutrer FM, Rosen BR, Tootell RB, Sorensen AG, Moskowitz MA. Mechanisms of migraine aura revealed by functional MRI in human visual cortex. Proc Natl Acad Sci U S A. 2001;98:4687–4692. doi: 10.1073/pnas.071582498. PubMed DOI PMC

Petrusic I, Zidverc-Trajkovic J. Cortical spreading depression: origins and paths as inferred from the sequence of events during migraine aura. Funct Neurol. 2014;29:207–212. PubMed PMC

Antal A, Temme J, Nitsche MA, Varga ET, Lang N, Paulus W. Altered motion perception in migraineurs: evidence for interictal cortical hyperexcitability. Cephalalgia. 2005;25:788–794. doi: 10.1111/j.1468-2982.2005.00949.x. PubMed DOI

Pierelli F, Iacovelli E, Bracaglia M, Serrao M, Coppola G. Abnormal sensorimotor plasticity in migraine without aura patients. Pain. 2013;154:1738–1742. doi: 10.1016/j.pain.2013.05.023. PubMed DOI

Aurora SK, Ahmad BK, Welch KM, Bhardhwaj P, Ramadan NM. Transcranial magnetic stimulation confirms hyperexcitability of occipital cortex in migraine. Neurology. 1998;50:1111–1114. doi: 10.1212/WNL.50.4.1111. PubMed DOI

Chadaide Z, Arlt S, Antal A, Nitsche MA, Lang N, Paulus W. Transcranial direct current stimulation reveals inhibitory deficiency in migraine. Cephalalgia. 2007;27:833–839. doi: 10.1111/j.1468-2982.2007.01337.x. PubMed DOI

Gawel M, Connolly JF, Rose FC. Migraine patients exhibit abnormalities in the visual evoked potential. Headache. 1983;23:49–52. doi: 10.1111/j.1526-4610.1983.hed2302049.x. PubMed DOI

Afra J, Proietti Cecchini A, Sandor PS, Schoenen J. Comparison of visual and auditory evoked cortical potentials in migraine patients between attacks. Clin Neurophysiol. 2000;111:1124–1129. doi: 10.1016/S1388-2457(00)00271-6. PubMed DOI

Brigo F, Storti M, Nardone R, Fiaschi A, Bongiovanni LG, Tezzon F, Manganotti P. Transcranial magnetic stimulation of visual cortex in migraine patients: a systematic review with meta-analysis. J Headache Pain. 2012;13:339–349. doi: 10.1007/s10194-012-0445-6. PubMed DOI PMC

Mantini D, Perrucci MG, Del Gratta C, Romani GL, Corbetta M. Electrophysiological signatures of resting state networks in the human brain. Proc Natl Acad Sci U S A. 2007;104:13170–13175. doi: 10.1073/pnas.0700668104. PubMed DOI PMC

Beckmann CF, DeLuca M, Devlin JT, Smith SM. Investigations into resting-state connectivity using independent component analysis. Philos T Roy Soc B. 2005;360:1001–1013. doi: 10.1098/rstb.2005.1634. PubMed DOI PMC

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(12):e52927. doi:10.1371/journal.pone.0052927 PubMed PMC

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 14:89. doi:10.1186/1129-2377-14-89 PubMed PMC

Yuan K, Zhao L, Cheng P, Yu DH, Zhao LM, Dong T, Xing LH, Bi YZ, Yang XJ, von Deneen KM, Liang FR, Gong QY, Qin W, Tian J. Altered structure and resting-state functional connectivity of the basal ganglia in migraine patients without aura. J Pain. 2013;14:836–844. doi: 10.1016/j.jpain.2013.02.010. PubMed DOI

Mainero C, Boshyan J, Hadjikhani N. Altered functional magnetic resonance imaging resting-state connectivity in periaqueductal gray networks in migraine. Ann Neurol. 2011;70:838–845. doi: 10.1002/ana.22537. PubMed DOI PMC

Tedeschi G, Russo A, Conte F, Corbo D, Caiazzo G, Giordano A, Conforti R, Esposito F, Tessitore A (2015) Increased interictal visual network connectivity in patients with migraine with aura. Cephalalgia: an international journal of headache. doi:10.1177/0333102415584360 PubMed

Hadjikhani N, Ward N, Boshyan J, Napadow V, Maeda Y, Truini A, Caramia F, Tinelli E, Mainero C. The missing link: enhanced functional connectivity between amygdala and visceroceptive cortex in migraine. Cephalalgia. 2013;33:1264–1268. doi: 10.1177/0333102413490344. PubMed DOI PMC

Niddam DM, Lai KL, Fuh JL, Chuang CY, Chen WT, Wang SJ (2015) Reduced functional connectivity between salience and visual networks in migraine with aura. Cephalalgia: an international journal of headache. doi:10.1177/0333102415583144 PubMed

Tessitore A, Russo A, Conte F, Giordano A, De Stefano M, Lavorgna L, Corbo D, Caiazzo G, Esposito F, Tedeschi G. Abnormal connectivity within executive resting-state network in migraine with aura. Headache. 2015;55:794–805. doi: 10.1111/head.12587. PubMed DOI

Hougaard A, Amin FM, Magon S, Sprenger T, Rostrup E, Ashina M. No abnormalities of intrinsic brain connectivity in the interictal phase of migraine with aura. Eur j neurol. 2015;22:702–e746. doi: 10.1111/ene.12636. PubMed DOI

Hougaard A, Amin FM, Hoffmann MB, Larsson HB, Magon S, Sprenger T, Ashina M. Structural gray matter abnormalities in migraine relate to headache lateralization, but not aura. Cephalalgia. 2015;35:3–9. doi: 10.1177/0333102414532378. PubMed DOI

Schwedt TJ, Schlaggar BL, Mar S, Nolan T, Coalson RS, Nardos B, Benzinger T, Larson-Prior LJ. Atypical resting-state functional connectivity of affective pain regions in chronic migraine. Headache. 2013;53:737–751. doi: 10.1111/head.12081. PubMed DOI PMC

Jin CW, Yuan K, Zhao LM, Zhao L, Yu DH, von Deneen KM, Zhang M, Qin W, Sun WX, Tian J. Structural and functional abnormalities in migraine patients without aura. NMR Biomed. 2013;26:58–64. doi: 10.1002/nbm.2819. PubMed DOI

Boyacioglu R, Beckmann CF, Barth M (2013) An investigation of RSN frequency spectra using ultra-fast generalized inverse imaging. Front Hum Neurosci 7:156. doi:10.3389/fnhum.2013.00156.eCollection PubMed PMC

Zou QH, Zhu CZ, Yang Y, Zuo XN, Long XY, Cao QJ, Wang YF, Zang YF. An improved approach to detection of amplitude of low-frequency fluctuation (ALFF) for resting-state fMRI: fractional ALFF. J Neurosci Methods. 2008;172:137–141. doi: 10.1016/j.jneumeth.2008.04.012. PubMed DOI PMC

Kim JY, Kim SH, Seo J, Kim SH, Han SW, Nam EJ, Kim SK, Lee HJ, Lee SJ, Kim YT, Chang Y. Increased power spectral density in resting-state pain-related brain networks in fibromyalgia. Pain. 2013;154:1792–1797. doi: 10.1016/j.pain.2013.05.040. PubMed DOI

Smith SM. Fast robust automated brain extraction. Hum Brain Mapp. 2002;17:143–155. doi: 10.1002/hbm.10062. PubMed DOI PMC

Jenkinson M, Bannister P, Brady M, Smith S. Improved optimization for the robust and accurate linear registration and motion correction of brain images. Neuroimage. 2002;17:825–841. doi: 10.1006/nimg.2002.1132. PubMed DOI

Beckmann CF, Smith SM. Tensorial extensions of independent component analysis for multisubject FMRI analysis. Neuroimage. 2005;25:294–311. doi: 10.1016/j.neuroimage.2004.10.043. PubMed DOI

Oelkers R, Grosser K, Lang E, Geisslinger G, Kobal G, Brune K, Lotsch J. Visual evoked potentials in migraine patients: alterations depend on pattern spatial frequency. Brain. 1999;122(Pt 6):1147–1155. doi: 10.1093/brain/122.6.1147. PubMed DOI

Connolly JF, Gawel M, Rose FC. Migraine patients exhibit abnormalities in the visual evoked potential. J Neurol Neurosurg Psychiatry. 1982;45:464–467. doi: 10.1136/jnnp.45.5.464. PubMed DOI PMC

Diener HC, Scholz E, Dichgans J, Gerber WD, Jack A, Bille A, Niederberger U. Central effects of drugs used in migraine prophylaxis evaluated by visual evoked potentials. Ann Neurol. 1989;25:125–130. doi: 10.1002/ana.410250204. PubMed DOI

Coppola G, Bracaglia M, Di Lenola D, Di Lorenzo C, Serrao M, Parisi V, Di Renzo A, Martelli F, Fadda A, Schoenen J, Pierelli F. Visual evoked potentials in subgroups of migraine with aura patients. J Headache Pain. 2015;16:92. doi: 10.1186/s10194-015-0577-6. PubMed DOI PMC

Sand T, Zhitniy N, White LR, Stovner LJ. Visual evoked potential latency, amplitude and habituation in migraine: a longitudinal study. Clin Neurophysiol. 2008;119:1020–1027. doi: 10.1016/j.clinph.2008.01.009. PubMed DOI

Brigo F, Storti M, Tezzon F, Manganotti P, Nardone R. Primary visual cortex excitability in migraine: a systematic review with meta-analysis. Neurol Sci. 2013;34:819–830. doi: 10.1007/s10072-012-1274-8. PubMed DOI

Vincent M, Pedra E, Mourao-Miranda J, Bramati IE, Henrique AR, Moll J. Enhanced interictal responsiveness of the migraineous visual cortex to incongruent bar stimulation: a functional MRI visual activation study. Cephalalgia. 2003;23:860–868. doi: 10.1046/j.1468-2982.2003.00609.x. PubMed DOI

Noseda R, Burstein R. Advances in understanding the mechanisms of migraine-type photophobia. Curr Opin Neurol. 2011;24:197–202. doi: 10.1097/WCO.0b013e3283466c8e. PubMed DOI PMC

Boulloche N, Denuelle M, Payoux P, Fabre N, Trotter Y, Geraud G. Photophobia in migraine: an interictal PET study of cortical hyperexcitability and its modulation by pain. J Neurol Neurosurg Psychiatry. 2010;81:978–984. doi: 10.1136/jnnp.2009.190223. PubMed DOI

Datta R, Aguirre GK, Hu S, Detre JA, Cucchiara B. Interictal cortical hyperresponsiveness in migraine is directly related to the presence of aura. Cephalalgia. 2013;33:365–374. doi: 10.1177/0333102412474503. PubMed DOI PMC

Cucchiara B, Datta R, Aguirre GK, Idoko KE, Detre J. Measurement of visual sensitivity in migraine: validation of two scales and correlation with visual cortex activation. Cephalalgia. 2015;35:585–592. doi: 10.1177/0333102414547782. PubMed DOI

Gonzalez de la Aleja J, Ramos A, Mato-Abad V, Martinez-Salio A, Hernandez-Tamames JA, Molina JA, Hernandez-Gallego J, Alvarez-Linera J. Higher glutamate to glutamine ratios in occipital regions in women with migraine during the interictal state. Headache. 2013;53:365–375. doi: 10.1111/head.12030. PubMed DOI

Bridge H, Stagg CJ, Near J, Lau CI, Zisner A, Cader MZ. Altered neurochemical coupling in the occipital cortex in migraine with visual aura. Cephalalgia. 2015;35:1025–1030. doi: 10.1177/0333102414566860. PubMed DOI

Sarchielli P, Tarducci R, Presciutti O, Gobbi G, Pelliccioli GP, Stipa G, Alberti A, Capocchi G. Functional 1H-MRS findings in migraine patients with and without aura assessed interictally. Neuroimage. 2005;24:1025–1031. doi: 10.1016/j.neuroimage.2004.11.005. PubMed DOI

Hougaard A, Amin FM, Hoffmann MB, Rostrup E, Larsson HB, Asghar MS, Larsen VA, Olesen J, Ashina M. Interhemispheric differences of fMRI responses to visual stimuli in patients with side-fixed migraine aura. Hum Brain Mapp. 2014;35:2714–2723. doi: 10.1002/hbm.22361. PubMed DOI PMC

Russo A, Tessitore A, Giordano A, Corbo D, Marcuccio L, De Stefano M, Salemi F, Conforti R, Esposito F, Tedeschi G. Executive resting-state network connectivity in migraine without aura. Cephalalgia. 2012;32:1041–1048. doi: 10.1177/0333102412457089. PubMed DOI

Ma X, Li S, Tian J, Jiang G, Wen H, Wang T, Fang J, Zhan W, Xu Y. Altered brain spontaneous activity and connectivity network in irritable bowel syndrome patients: a resting-state fMRI study. Clin Neurophysiol. 2015;126:1190–1197. doi: 10.1016/j.clinph.2014.10.004. PubMed DOI

Baliki MN, Mansour AR, Baria AT, Apkarian AV. Functional reorganization of the default mode network across chronic pain conditions. PLoS One. 2014;9:e106133. doi: 10.1371/journal.pone.0106133. PubMed DOI PMC

Wang JJ, Chen X, Sah SK, Zeng C, Li YM, Li N, Liu MQ, Du SL. Amplitude of low-frequency fluctuation (ALFF) and fractional ALFF in migraine patients: a resting-state functional MRI study. Clin Radiol. 2016;71:558–564. doi: 10.1016/j.crad.2016.03.004. PubMed DOI

Gao L, Bai L, Zhang Y, Dai XJ, Netra R, Min Y, Zhou F, Niu C, Dun W, Gong H, Zhang M. Frequency-dependent changes of local resting oscillations in sleep-deprived brain. PLoS One. 2015;10:e0120323. doi: 10.1371/journal.pone.0120323. PubMed DOI PMC

Otti A, Guendel H, Wohlschlager A, Zimmer C, Noll-Hussong M. Frequency shifts in the anterior default mode network and the salience network in chronic pain disorder. BMC Psychiatry. 2013;13:84. doi: 10.1186/1471-244X-13-84. PubMed DOI PMC

Salvador R, Martinez A, Pomarol-Clotet E, Gomar J, Vila F, Sarro S, Capdevila A, Bullmore E. A simple view of the brain through a frequency-specific functional connectivity measure. Neuroimage. 2008;39:279–289. doi: 10.1016/j.neuroimage.2007.08.018. PubMed DOI

Malinen S, Vartiainen N, Hlushchuk Y, Koskinen M, Ramkumar P, Forss N, Kalso E, Hari R. Aberrant temporal and spatial brain activity during rest in patients with chronic pain. Proc Natl Acad Sci U S A. 2010;107:6493–6497. doi: 10.1073/pnas.1001504107. PubMed DOI PMC

Boyacioglu R, Beckmann CF, Barth M. An investigation of RSN frequency spectra using ultra-fast generalized inverse imaging. Front Hum Neurosci. 2013;7:156. doi: 10.3389/fnhum.2013.00156. PubMed DOI PMC

Lee MC, Tracey I. Imaging pain: a potent means for investigating pain mechanisms in patients. Br J Anaesth. 2013;111:64–72. doi: 10.1093/bja/aet174. PubMed DOI PMC

Davis KD, Moayedi M. Central mechanisms of pain revealed through functional and structural MRI. J Neuroimmune Pharmacol. 2013;8:518–534. doi: 10.1007/s11481-012-9386-8. PubMed DOI

Bliss TV, Collingridge GL, Kaang B-K, Zhuo M (2016) Synaptic plasticity in the anterior cingulate cortex in acute and chronic pain. Nature Reviews Neuroscience PubMed

Cohen S, Mao J. Neuropathic Pain: Mechanisms & Clinical Implications + MP3. Br Med J. 2014;348:f7656. doi: 10.1136/bmj.f7656. PubMed DOI

Treede R-D, Kenshalo DR, Gracely RH, Jones AK. The cortical representation of pain. Pain. 1999;79:105–111. doi: 10.1016/S0304-3959(98)00184-5. PubMed DOI

Denk F, McMahon SB, Tracey I. Pain vulnerability: a neurobiological perspective. Nat Neurosci. 2014;17:192–200. doi: 10.1038/nn.3628. PubMed DOI

Floyd NS, Price JL, Ferry AT, Keay KA, Bandler R. Orbitomedial prefrontal cortical projections to distinct longitudinal columns of the periaqueductal gray in the rat. J Comp Neurol. 2000;422:556–578. doi: 10.1002/1096-9861(20000710)422:4<556::AID-CNE6>3.0.CO;2-U. PubMed DOI

Spisak T, Pozsgay Z, Aranyi C, David S, Kocsis P, Nyitrai G, Gajari D, Emri M, Czurko A, Kincses ZT, Central sensitization related changes of effective and functional connectivity in the rat inflammatory trigeminal pain model. Neuroscience (in press) PubMed

Moulton EA, Schmahmann JD, Becerra L, Borsook D. The cerebellum and pain: passive integrator or active participator? Brain Res Rev. 2010;65:14–27. doi: 10.1016/j.brainresrev.2010.05.005. PubMed DOI PMC

Sandor PS, Mascia A, Seidel L, de Pasqua V, Schoenen J. Subclinical cerebellar impairment in the common types of migraine: a three-dimensional analysis of reaching movements. Ann Neurol. 2001;49:668–672. doi: 10.1002/ana.1019. PubMed DOI

Harno H, Hirvonen T, Kaunisto MA, Aalto H, Levo H, Isotalo E, Kallela M, Kaprio J, Palotie A, Wessman M, Farkkila M. Subclinical vestibulocerebellar dysfunction in migraine with and without aura. Neurology. 2003;61:1748–1752. doi: 10.1212/01.WNL.0000098882.82690.65. PubMed DOI

Granziera C, Romascano D, Daducci A, Roche A, Vincent M, Krueger G, Hadjikhani N. Migraineurs without aura show microstructural abnormalities in the cerebellum and frontal lobe. Cerebellum. 2013;12:812–818. doi: 10.1007/s12311-013-0491-x. PubMed DOI

Jin C, Yuan K, Zhao L, Zhao L, Yu D, von Deneen KM, Zhang M, Qin W, Sun W, Tian J. Structural and functional abnormalities in migraine patients without aura. NMR Biomed. 2013;26:58–64. doi: 10.1002/nbm.2819. PubMed DOI

Arkink EB, Bleeker EJ, Schmitz N, Schoonman GG, Wu O, Ferrari MD, van Buchem MA, van Osch MJ, Kruit MC. Cerebral perfusion changes in migraineurs: a voxelwise comparison of interictal dynamic susceptibility contrast MRI measurements. Cephalalgia. 2012;32:279–288. doi: 10.1177/0333102411435985. PubMed DOI PMC

O’Bryant SE, Marcus DA, Rains JC, Penzien DB. Neuropsychology of migraine: present status and future directions. Expert Rev Neurother. 2005;5:363–370. doi: 10.1586/14737175.5.3.363. PubMed DOI

Camarda C, Monastero R, Pipia C, Recca D, Camarda R. Interictal executive dysfunction in migraineurs without aura: relationship with duration and intensity of attacks. Cephalalgia. 2007;27:1094–1100. doi: 10.1111/j.1468-2982.2007.01394.x. PubMed DOI

Are Migraine With and Without Aura Really Different Entities?

Altered Resting State Functional Activity and Microstructure of the White Matter in Migraine With Aura

Evidence for Plastic Processes in Migraine with Aura: A Diffusion Weighted MRI Study