Advertisement

Changes in grey matter volume and functional connectivity in cluster headache versus migraine

  • Antonio GiorgioEmail author
  • Chiara Lupi
  • Jian Zhang
  • Francesco De Cesaris
  • Mario Alessandri
  • Marzia Mortilla
  • Antonio Federico
  • Pierangelo Geppetti
  • Nicola De Stefano
  • Silvia Benemei
ORIGINAL RESEARCH

Abstract

Cluster headache (CH) shows a more severe clinical picture than migraine (Mig). We tested whether brain changes can explain such difference. Multimodal MRI was acquired in attack-free patients with CH (n = 12), Mig (n = 13) and in normal controls (NC, n = 13). We used FSL for MRI data analysis and nonparametric permutation testing for voxelwise analyses (p < 0.01, corrected). CH showed lower grey matter (GM) volume, compared to Mig and NC, in frontal cortex regions (inferior frontal gyrus and frontal pole [FP], respectively) and, only compared to Mig, in lateral occipital cortex (LOC). Functional connectivity (FC) of CH was higher than Mig and NC within working memory and executive control networks and, only compared to Mig, between cerebellar and auditory language comprehension networks. In the attack-free state, the CH brain seems to be characterized by: (i) GM volume decrease, compared to both Mig and NC, in pain modulation regions (FP) and, only with respect to Mig, in a region of visual processing modulation during pain and working memory (LOC); (ii) increased FC at short range compared to both Mig and NC and at long range only with respect to Mig, in key cognitive networks, likely due to maladaptation towards more severe pain experience.

Keywords

Cluster headache Migraine MRI Volumetry Connectivity 

Notes

Acknowledgements

Riccardo Tappa Brocci (University of Siena) helped with MRI data acquisition; Mary Lokken revised the manuscript for English language editing.

Author’s contribution

Antonio Giorgio, study concept, acquisition, analysis and interpretation of data, manuscript writing. Chiara Lupi, study concept and design, acquisition of data, manuscript writing. Jian Zhang, acquisition, analysis of data. Francesco De Cesaris, acquisition of data. Mario Alessandri, acquisition of data. Marzia Mortilla, acquisition of data. Antonio Federico, critical revision of manuscript for intellectual content. Pierangelo Geppetti, critical revision of manuscript for intellectual content. Nicola De Stefano, critical revision of manuscript for intellectual content. Silvia Benemei, study concept and design, study supervision, critical revision of manuscript for intellectual content.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest specific for this study.

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the local Institutional Ethics Committee on Clinical Research and with the Helsinki Declaration (version amended during the 64th WMA General Assembly, Fortaleza, Brazil, October 2013). Written informed consent was obtained from all participants before study entry.

References

  1. (IHS) HCCotIHS. (2013). The international classification of headache disorders, 3rd edition (beta version). Cephalalgia, 33(9), 629–808.CrossRefGoogle Scholar
  2. Absinta, M., Rocca, M. A., Colombo, B., Falini, A., Comi, G., & Filippi, M. (2012). Selective decreased grey matter volume of the pain-matrix network in cluster headache. Cephalalgia, 32(2), 109–115.CrossRefGoogle Scholar
  3. Arkink, E. B., Schmitz, N., Schoonman, G. G., van Vliet, J. A., Haan, J., van Buchem, M. A., Ferrari, M. D., & Kruit, M. C. (2017). The anterior hypothalamus in cluster headache. Cephalalgia, 37(11), 1039–1050.CrossRefGoogle Scholar
  4. Baliki, M. N., Mansour, A. R., Baria, A. T., & Apkarian, A. V. (2014). Functional reorganization of the default mode network across chronic pain conditions. PLoS One, 9(9), e106133.CrossRefGoogle Scholar
  5. Baumann, O., & Mattingley, J. B. (2010). Scaling of neural responses to visual and auditory motion in the human cerebellum. The Journal of Neuroscience, 30(12), 4489–4495.CrossRefGoogle Scholar
  6. Berryman, C., Stanton, T. R., Jane Bowering, K., Tabor, A., McFarlane, A., & Lorimer Moseley, G. (2013). Evidence for working memory deficits in chronic pain: a systematic review and meta-analysis. Pain, 154(8), 1181–1196.CrossRefGoogle Scholar
  7. Bingel, U., Rose, M., Glascher, J., & Buchel, C. (2007). fMRI reveals how pain modulates visual object processing in the ventral visual stream. Neuron, 55(1), 157–167.CrossRefGoogle Scholar
  8. 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. The Journal of Headache and Pain, 17(1), 89.CrossRefGoogle Scholar
  9. Chou, K. H., Yang, F. C., Fuh, J. L., Huang, C. C., Lirng, J. F., Lin, Y. Y., Lee, P. L., Kao, H. W., Lin, C. P., & Wang, S. J. (2014). Altered white matter microstructural connectivity in cluster headaches: a longitudinal diffusion tensor imaging study. Cephalalgia, 34(13), 1040–1052.CrossRefGoogle Scholar
  10. Dobromyslin, V. I., Salat, D. H., Fortier, C. B., Leritz, E. C., Beckmann, C. F., Milberg, W. P., & McGlinchey, R. E. (2012). Distinct functional networks within the cerebellum and their relation to cortical systems assessed with independent component analysis. Neuroimage, 60(4), 2073–2085.CrossRefGoogle Scholar
  11. Dresler, T., Lurding, R., Paelecke-Habermann, Y., Gaul, C., Henkel, K., Lindwurm-Spath, A., Leinisch, E., & Jurgens, T. P. (2012). Cluster headache and neuropsychological functioning. Cephalalgia, 32(11), 813–821.CrossRefGoogle Scholar
  12. Fazekas, F., Chawluk, J. B., Alavi, A., Hurtig, H. I., & Zimmerman, R. A. (1987). MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. AJR. American Journal of Roentgenology, 149(2), 351–356.CrossRefGoogle Scholar
  13. Granziera, C., DaSilva, A. F., Snyder, J., Tuch, D. S., & Hadjikhani, N. (2006). Anatomical alterations of the visual motion processing network in migraine with and without aura. PLoS Medicine, 3(10), e402.CrossRefGoogle Scholar
  14. Habas, C., Guillevin, R., & Abanou, A. (2011). Functional connectivity of the superior human temporal sulcus in the brain resting state at 3T. Neuroradiology, 53(2), 129–140.CrossRefGoogle Scholar
  15. Hadjipavlou, G., Dunckley, P., Behrens, T. E., & Tracey, I. (2006). Determining anatomical connectivities between cortical and brainstem pain processing regions in humans: a diffusion tensor imaging study in healthy controls. Pain, 123(1–2), 169–178.CrossRefGoogle Scholar
  16. Hoffmann, J., & May, A. (2018). Diagnosis, pathophysiology, and management of cluster headache. Lancet Neurology, 17(1), 75–83.CrossRefGoogle Scholar
  17. Jenkinson, M., & Smith, S. (2001). A global optimisation method for robust affine registration of brain images. Medical Image Analysis, 5(2), 143–156.CrossRefGoogle Scholar
  18. Jin, C., Yuan, K., Zhao, L., Yu, D., von Deneen, K. M., Zhang, M., Qin, W., Sun, W., & Tian, J. (2013). Structural and functional abnormalities in migraine patients without aura. NMR in Biomedicine, 26(1), 58–64.CrossRefGoogle Scholar
  19. Kim, J. H., Suh, S. I., Seol, H. Y., Oh, K., Seo, W. K., Yu, S. W., Park, K. W., & Koh, S. B. (2008). Regional grey matter changes in patients with migraine: a voxel-based morphometry study. Cephalalgia, 28(6), 598–604.CrossRefGoogle Scholar
  20. Liu, G., Ma, H. J., Hu, P. P., Tian, Y. H., Hu, S., Fan, J., & Wang, K. (2013). Effects of painful stimulation and acupuncture on attention networks in healthy subjects. Behavioral and Brain Functions, 9, 23.CrossRefGoogle Scholar
  21. McLachlan, N. M., & Wilson, S. J. (2017). The contribution of brainstem and cerebellar pathways to auditory recognition. Frontiers in Psychology, 8, 265.CrossRefGoogle Scholar
  22. Messina, R., Rocca, M. A., Colombo, B., Valsasina, P., Horsfield, M. A., Copetti, M., Falini, A., Comi, G., & Filippi, M. (2013). Cortical abnormalities in patients with migraine: a surface-based analysis. Radiology, 268(1), 170–180.CrossRefGoogle Scholar
  23. Moberget, T., & Ivry, R. B. (2016). Cerebellar contributions to motor control and language comprehension: searching for common computational principles. Annals of the New York Academy of Sciences, 1369(1), 154–171.CrossRefGoogle Scholar
  24. Naegel, S., Holle, D., Desmarattes, N., Theysohn, N., Diener, H. C., Katsarava, Z., & Obermann, M. (2014a). Cortical plasticity in episodic and chronic cluster headache. NeuroImage: Clinical, 6, 415–423.CrossRefGoogle Scholar
  25. Naegel, S., Holle, D., & Obermann, M. (2014b). Structural imaging in cluster headache. Current Pain and Headache Reports, 18(5), 415.CrossRefGoogle Scholar
  26. Neeb, L., Bastian, K., Villringer, K., Gits, H. C., Israel, H., Reuter, U., & Fiebach, J. B. (2015). No microstructural white matter alterations in chronic and episodic migraineurs: a case-control diffusion tensor magnetic resonance imaging study. Headache, 55(2), 241–251.CrossRefGoogle Scholar
  27. Oguz, I., Farzinfar, M., Matsui, J., Budin, F., Liu, Z., Gerig, G., Johnson, H. J., & Styner, M. (2014). DTIPrep: quality control of diffusion-weighted images. Frontiers in Neuroinformatics, 8, 4.CrossRefGoogle Scholar
  28. Pruim, R. H., Mennes, M., van Rooij, D., Llera, A., Buitelaar, J. K., & Beckmann, C. F. (2015). ICA-AROMA: a robust ICA-based strategy for removing motion artifacts from fMRI data. Neuroimage, 112, 267–277.CrossRefGoogle Scholar
  29. Qiu, E., Wang, Y., Ma, L., Tian, L., Liu, R., Dong, Z., Xu, X., Zou, Z., & Yu, S. (2013). Abnormal brain functional connectivity of the hypothalamus in cluster headaches. PLoS One, 8(2), e57896.CrossRefGoogle Scholar
  30. Rocca, M. A., Ceccarelli, A., Falini, A., Colombo, B., Tortorella, P., Bernasconi, L., Comi, G., Scotti, G., & Filippi, M. (2006). Brain gray matter changes in migraine patients with T2-visible lesions: a 3-T MRI study. Stroke, 37(7), 1765–1770.CrossRefGoogle Scholar
  31. Sprenger, T., Ruether, K. V., Boecker, H., Valet, M., Berthele, A., Pfaffenrath, V., Woller, A., & Tolle, T. R. (2007). Altered metabolism in frontal brain circuits in cluster headache. Cephalalgia, 27(9), 1033–1042.CrossRefGoogle Scholar
  32. Szabo, N., Kincses, Z. T., Pardutz, A., Toth, E., Szok, D., Csete, G., & Vecsei, L. (2013). White matter disintegration in cluster headache. The Journal of Headache and Pain, 14, 64.CrossRefGoogle Scholar
  33. Teepker, M., Menzler, K., Belke, M., Heverhagen, J. T., Voelker, M., Mylius, V., Oertel, W. H., Rosenow, F., & Knake, S. (2012). Diffusion tensor imaging in episodic cluster headache. Headache, 52(2), 274–282.CrossRefGoogle Scholar
  34. Torkamani, M., Ernst, L., Cheung, L. S., Lambru, G., Matharu, M., & Jahanshahi, M. (2015). The neuropsychology of cluster headache: cognition, mood, disability, and quality of life of patients with chronic and episodic cluster headache. Headache, 55(2), 287–300.CrossRefGoogle Scholar
  35. Valfre, W., Rainero, I., Bergui, M., & Pinessi, L. (2008). Voxel-based morphometry reveals gray matter abnormalities in migraine. Headache, 48(1), 109–117.CrossRefGoogle Scholar
  36. Yang, F. C., Chou, K. H., Fuh, J. L., Huang, C. C., Lirng, J. F., Lin, Y. Y., Lin, C. P., & Wang, S. J. (2013). Altered gray matter volume in the frontal pain modulation network in patients with cluster headache. Pain, 154(6), 801–807.CrossRefGoogle Scholar
  37. Yang, F. C., Chou, K. H., Fuh, J. L., Lee, P. L., Lirng, J. F., Lin, Y. Y., Lin, C. P., & Wang, S. J. (2014). Altered hypothalamic functional connectivity in cluster headache: a longitudinal resting-state functional MRI study. Journal of Neurology, Neurosurgery, and Psychiatry, 86(4), 437–445.CrossRefGoogle Scholar
  38. Yu, D., Yuan, K., Qin, W., Zhao, L., Dong, M., Liu, P., Yang, X., Liu, J., Sun, J., Zhou, G., von Deneen, K. M., & Tian, J. (2013). Axonal loss of white matter in migraine without aura: a tract-based spatial statistics study. Cephalalgia, 33(1), 34–42.CrossRefGoogle Scholar
  39. Yu, Z. B., Lv, Y. B., Song, L. H., Liu, D. H., Huang, X. L., Hu, X. Y., Zuo, Z. W., Wang, Y., Yang, Q., Peng, J., Zhou, Z. H., & Li, H. T. (2017). Functional connectivity differences in the insular sub-regions in migraine without Aura: a resting-state functional magnetic resonance imaging study. Frontiers in Behavioral Neuroscience, 11, 124.CrossRefGoogle Scholar
  40. Yuan, K., Qin, W., Liu, P., Zhao, L., Yu, D., Dong, M., Liu, J., Yang, X., von Deneen, K. M., 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(9), e45476.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Antonio Giorgio
    • 1
    Email author
  • Chiara Lupi
    • 2
  • Jian Zhang
    • 1
  • Francesco De Cesaris
    • 2
  • Mario Alessandri
    • 2
  • Marzia Mortilla
    • 3
  • Antonio Federico
    • 1
  • Pierangelo Geppetti
    • 2
  • Nicola De Stefano
    • 1
  • Silvia Benemei
    • 2
  1. 1.Department of Medicine, Surgery and NeuroscienceUniversity of SienaSienaItaly
  2. 2.Headache Centre, Careggi University Hospital, Department of Health SciencesUniversity of FlorenceFlorenceItaly
  3. 3.Anna Meyer Children’s University HospitalFlorenceItaly

Personalised recommendations