Insular functional connectivity in migraine with aura

Cédric Gollion, Fleur Lerebours, Federico Nemmi, Germain Arribarat, Fabrice Bonneville, Vincent Larrue, Patrice Péran, Cédric Gollion, Fleur Lerebours, Federico Nemmi, Germain Arribarat, Fabrice Bonneville, Vincent Larrue, Patrice Péran

Abstract

Introduction: Insula plays an integrating role in sensory, affective, emotional, cognitive and autonomic functions in migraine, especially in migraine with aura (MA). Insula is functionally divided into 3 subregions, the dorsoanterior, the ventroanterior and the posterior insula respectively related to cognition, emotion, and somatosensory functions. This study aimed at investigating functional connectivity of insula subregions in MA.

Methods: Twenty-one interictal patients with MA were compared to 18 healthy controls (HC) and 12 interictal patients with migraine without aura (MO) and were scanned with functional MRI during the resting state. Functional coupling of the insula was comprehensively tested with 12 seeds located in the right and left, dorsal, middle, ventral, anterior and posterior insula, by using a seed-to-voxel analysis.

Results: Seed-to-voxel analysis revealed, in MA, a strong functional coupling of the right and left antero-dorsal insula with clusters located in the upper cerebellum. The overlap of these cerebellar clusters corresponded to the vermis VI. These functional couplings were not correlated to duration of MA, frequency of MA attacks nor time since last MA attack, and were not found in MO.

Discussion: The anterior insula and superior cerebellum, including vermis VI, are components of the central Autonomic Nervous System (ANS) network. As these regions are involved in the control of cardiovascular parasympathetic tone, we hypothesize that this connectivity may reflect the cardiovascular features of MA.

Conclusion: The anterior dorsal insula is connected with vermis VI in MA patients in the resting state. This connectivity may reflect the cardiovascular features of MA.

Trial registration: NCT02708797.

Keywords: Cerebellum vermis; Functional MRI; Insula; MRI; Migraine; Migraine with aura.

Conflict of interest statement

Authors report no disclosure related to this paper.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Region of interest (ROI) located in the dorsal (A), middle (B) and ventral(C) insula. These ROI were considered as seeds in the seed-to-voxel analysis. MNI coordinates are given in Table 1
Fig. 2
Fig. 2
Increased connectivity between ROI 1, antero-dorsal insula, right (A) and left (B) with cerebellum in MA
Fig. 3
Fig. 3
Overlap (purple) of areas highly connected to the right (red) and left (blue) antero-dorsal insula, corresponding to vermis VI
Fig. 4
Fig. 4
ROI-to-ROI functional coupling of vermis VI with right (ROI 1 R) and left (ROI 1 L) antero-dorsal insula. HC = healthy controls. MA = migraine with aura

References

    1. GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global burden of disease study 2016. Lancet. 2017;390(10100):1211–59. 10.1016/S0140-6736(17)32154-2.
    1. Stovner LJ, Hagen K, Linde M, Steiner TJ. The global prevalence of headache: an update, with analysis of the influences of methodological factors on prevalence estimates. J Headache Pain. 2022;23(1):34. doi: 10.1186/s10194-022-01402-2.
    1. Ashina M. Migraine. New England Journal of Medicine [Internet]. 2020 Nov 4 [cited 2021 Mar 10]; Available from: 10.1056/NEJMra1915327
    1. Burstein R, Noseda R, Borsook D. Migraine: multiple processes, complex pathophysiology. J Neurosci. 2015;35(17):6619–6629. doi: 10.1523/JNEUROSCI.0373-15.2015.
    1. Uddin LQ, Nomi JS, Hébert-Seropian B, Ghaziri J, Boucher O. Structure and function of the human insula. J Clin Neurophysiol. 2017;34(4):300–306. doi: 10.1097/WNP.0000000000000377.
    1. Glasser MF, Coalson TS, Robinson EC, Hacker CD, Harwell J, Yacoub E, et al. A multi-modal parcellation of human cerebral cortex. Nat. 2016;536(7615):171–178. doi: 10.1038/nature18933.
    1. Chang LJ, Yarkoni T, Khaw MW, Sanfey AG. Decoding the role of the insula in human cognition: functional parcellation and large-scale reverse inference. Cereb Cortex. 2013;23(3):739–749. doi: 10.1093/cercor/bhs065.
    1. Afridi SK, Giffin NJ, Kaube H, Friston KJ, Ward NS, Frackowiak RSJ, et al. A positron emission tomographic study in spontaneous migraine. Arch Neurol. 2005;62(8):1270–1275. doi: 10.1001/archneur.62.8.1270.
    1. Denuelle M, Fabre N, Payoux P, Chollet F, Geraud G. Hypothalamic activation in spontaneous migraine attacks. Headache. 2007;47(10):1418–1426.
    1. Stankewitz A, May A. Increased limbic and brainstem activity during migraine attacks following olfactory stimulation. Neurol. 2011;77(5):476–482. doi: 10.1212/WNL.0b013e318227e4a8.
    1. Coppola G, Di Renzo A, Tinelli E, Di Lorenzo C, Scapeccia M, Parisi V, et al. Resting state connectivity between default mode network and insula encodes acute migraine headache. Cephalalgia. 2018;38(5):846–854. doi: 10.1177/0333102417715230.
    1. Amin FM, Hougaard A, Magon S, Sprenger T, Wolfram F, Rostrup E, et al. Altered thalamic connectivity during spontaneous attacks of migraine without aura: A resting-state fMRI study. Cephalalgia. 2018;38(7):1237–1244. doi: 10.1177/0333102417729113.
    1. Ke J, Yu Y, Zhang X, Su Y, Wang X, Hu S, et al. Functional alterations in the posterior insula and cerebellum in migraine without aura: A resting-state MRI study. frontiers in behavioral neuroscience [Internet]. 2020 [cited 2022 Jun 7];14. Available from: 10.3389/fnbeh.2020.567588.
    1. Maleki N, Becerra L, Brawn J, Bigal M, Burstein R, Borsook D. Concurrent functional and structural cortical alterations in migraine. Cephalalgia. 2012;32(8):607–20. doi: 10.1177/0333102412445622.
    1. Schwedt TJ, Schlaggar BL, Mar S, Nolan T, Coalson RS, Nardos B, et al. Atypical resting-state functional connectivity of affective pain regions in chronic migraine. Headache. 2013;53(5):737–751. doi: 10.1111/head.12081.
    1. Borsook D, Veggeberg R, Erpelding N, Borra R, Linnman C, Burstein R, et al. The insula: A ‘hub of activity’ in migraine. Neuroscientist. 2016;22(6):632–652. doi: 10.1177/1073858415601369.
    1. Niddam DM, Lai KL, Fuh JL, Chuang CYN, Chen WT, Wang SJ. Reduced functional connectivity between salience and visual networks in migraine with aura. Cephalalgia. 2016;36(1):53–66. doi: 10.1177/0333102415583144.
    1. Silvestro M, Tessitore A, Di Nardo F, Scotto di Clemente F, Trojsi F, Cirillo M, et al. Functional connectivity changes in complex migraine aura: beyond the visual network. Eur J Neurol. 2022;29(1):295–304. doi: 10.1111/ene.15061.
    1. Albrecht DS, Mainero C, Ichijo E, Ward N, Granziera C, Zürcher NR, et al. Imaging of neuroinflammation in migraine with aura: A [11C]PBR28 PET/MRI study. Neurol. 2019;92(17):e2038–e2050. doi: 10.1212/WNL.0000000000007371.
    1. Androulakis XM, Krebs K, Peterlin BL, Zhang T, Maleki N, Sen S, et al. Modulation of intrinsic resting-state fMRI networks in women with chronic migraine. Neurol. 2017;89(2):163–169. doi: 10.1212/WNL.0000000000004089.
    1. Yu D, Yuan K, Luo L, Zhai J, Bi Y, Xue T, et al. Abnormal functional integration across core brain networks in migraine without aura. Mol Pain. 2017;13:1744806917737461. doi: 10.1177/1744806917737461.
    1. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018;38(1):1–211.
    1. Lerebours F, Boulanouar K, Barège M, Denuelle M, Bonneville F, Payoux P, et al. Functional connectivity of hypothalamus in chronic migraine with medication overuse. Cephalalgia. 2019;39(7):892–899. doi: 10.1177/0333102419833087.
    1. Cauda F, D’Agata F, Sacco K, Duca S, Geminiani G, Vercelli A. Functional connectivity of the insula in the resting brain. Neuroimage. 2011;55(1):8–23. doi: 10.1016/j.neuroimage.2010.11.049.
    1. Diedrichsen J, Balsters JH, Flavell J, Cussans E, Ramnani N. A probabilistic MR atlas of the human cerebellum. Neuroimage. 2009;46(1):39–46. doi: 10.1016/j.neuroimage.2009.01.045.
    1. Mainero C, Boshyan J, Hadjikhani N. Altered functional magnetic resonance imaging resting-state connectivity in periaqueductal gray networks in migraine. Ann Neurol. 2011;70(5):838–845. doi: 10.1002/ana.22537.
    1. Schwedt TJ, Larson-Prior L, Coalson RS, Nolan T, Mar S, Ances BM, et al. Allodynia and descending pain modulation in migraine: a resting state functional connectivity analysis. Pain Med. 2014;15(1):154–165. doi: 10.1111/pme.12267.
    1. Xue T, Yuan K, Zhao L, Yu D, Zhao L, Dong T, et al. Intrinsic brain network abnormalities in migraines without aura revealed in resting-state fMRI. Plos One. 2012;7(12):e52927. doi: 10.1371/journal.pone.0052927.
    1. Moulton EA, Schmahmann JD, Becerra L, Borsook D. The cerebellum and pain: passive integrator or active participator? Brain Res Rev. 2010;65(1):14–27. doi: 10.1016/j.brainresrev.2010.05.005.
    1. Mehnert J, Schulte L, Timmann D, May A. Activity and connectivity of the cerebellum in trigeminal nociception. Neuroimage. 2017;15(150):112–118. doi: 10.1016/j.neuroimage.2017.02.023.
    1. Mehnert J, May A. Functional and structural alterations in the migraine cerebellum. J Cereb Blood Flow Metab. 2019;39(4):730–739. doi: 10.1177/0271678X17722109.
    1. Russo A, Tessitore A, Esposito F, Marcuccio L, Giordano A, Conforti R, et al. Pain processing in patients with migraine: an event-related fMRI study during trigeminal nociceptive stimulation. J Neurol. 2012;259(9):1903–1912. doi: 10.1007/s00415-012-6438-1.
    1. Moulton EA, Becerra L, Maleki N, Pendse G, Tully S, Hargreaves R, et al. Painful heat reveals hyperexcitability of the temporal pole in interictal and ictal migraine States. Cereb Cortex. 2011;21(2):435–448. doi: 10.1093/cercor/bhq109.
    1. Schwedt TJ, Chong CD, Chiang CC, Baxter L, Schlaggar BL, Dodick DW. Enhanced pain-induced activity of pain processing Regions in a case-control study of episodic migraine. Cephalalgia. 2014;34(12):947–958. doi: 10.1177/0333102414526069.
    1. Ruiz Vargas E, Sörös P, Shoemaker JK, Hachinski V. Human cerebral circuitry related to cardiac control: A neuroimaging meta-analysis. Ann Neurol. 2016;79(5):709–716. doi: 10.1002/ana.24642.
    1. Kimmerly DS. A review of human neuroimaging investigations involved with central autonomic regulation of baroreflex-mediated cardiovascular control. Auton Neurosci. 2017;207:10–21. doi: 10.1016/j.autneu.2017.05.008.
    1. Macey PM, Ogren JA, Kumar R, Harper RM. Functional imaging of autonomic regulation: Methods and key findings. Front Neurosci. 2015;9:513.
    1. Beissner F, Meissner K, Bär KJ, Napadow V. The autonomic brain: an activation likelihood estimation meta-analysis for central processing of autonomic function. J Neurosci. 2013;33(25):10503–10511. doi: 10.1523/JNEUROSCI.1103-13.2013.
    1. Critchley HD, Corfield DR, Chandler MP, Mathias CJ, Dolan RJ. Cerebral correlates of autonomic cardiovascular arousal: a functional neuroimaging investigation in humans. J Physiol. 2000;15(523 Pt 1):259–270. doi: 10.1111/j.1469-7793.2000.t01-1-00259.x.
    1. Baker J, Paturel JR, Kimpinski K. Cerebellar impairment during an orthostatic challenge in patients with neurogenic orthostatic hypotension. Clin Neurophysiol. 2019;130(1):189–195. doi: 10.1016/j.clinph.2018.07.026.
    1. Baker J, Kimpinski K. Evidence of impaired cerebellar connectivity at rest and during autonomic maneuvers in patients with autonomic failure. Cerebellum. 2020;19(1):30–39. doi: 10.1007/s12311-019-01076-8.
    1. Thijs RD. Syncope in migraine: the population-based camera study. Neurol. 2006;66:1034–1037. doi: 10.1212/01.wnl.0000204186.43597.66.
    1. Kuan AS, Chen SP, Wang YF, Fuh JL, Cheng CY, Peng KP, et al. Risk factors and psychological impact of syncope in migraine patients. Cephalalgia. 2019;39(14):1838–1846. doi: 10.1177/0333102419865253.
    1. Miglis MG. Migraine and autonomic dysfunction: which is the horse and which is the jockey? Curr Pain Headache Rep. 2018;22(3):19. doi: 10.1007/s11916-018-0671-y.
    1. Dai YJ, Zhang X, Yang Y, Nan HY, Yu Y, Sun Q, et al. Gender differences in functional connectivities between insular subdivisions and selective pain-related brain structures. J Headache Pain. 2018;19(1):24. doi: 10.1186/s10194-018-0849-z.

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