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

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.

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References

  • (IHS) HCCotIHS. (2013). The international classification of headache disorders, 3rd edition (beta version). Cephalalgia, 33(9), 629–808.

    Article  Google Scholar 

  • 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.

    PubMed  Article  Google Scholar 

  • 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.

    PubMed  Article  Google Scholar 

  • 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.

    PubMed  PubMed Central  Article  Google Scholar 

  • 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.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 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.

    PubMed  Article  Google Scholar 

  • 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.

    CAS  PubMed  Article  Google Scholar 

  • 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.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 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.

    PubMed  Article  Google Scholar 

  • 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.

    PubMed  PubMed Central  Article  Google Scholar 

  • 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.

    PubMed  Article  Google Scholar 

  • 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.

    CAS  PubMed  Article  Google Scholar 

  • 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.

    PubMed  PubMed Central  Article  Google Scholar 

  • 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.

    PubMed  Article  Google Scholar 

  • 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.

    PubMed  Article  Google Scholar 

  • Hoffmann, J., & May, A. (2018). Diagnosis, pathophysiology, and management of cluster headache. Lancet Neurology, 17(1), 75–83.

    PubMed  Article  Google Scholar 

  • Jenkinson, M., & Smith, S. (2001). A global optimisation method for robust affine registration of brain images. Medical Image Analysis, 5(2), 143–156.

    CAS  PubMed  Article  Google Scholar 

  • 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.

    PubMed  Article  Google Scholar 

  • 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.

    CAS  PubMed  Article  Google Scholar 

  • 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.

    PubMed  Article  Google Scholar 

  • McLachlan, N. M., & Wilson, S. J. (2017). The contribution of brainstem and cerebellar pathways to auditory recognition. Frontiers in Psychology, 8, 265.

    PubMed  PubMed Central  Article  Google Scholar 

  • 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.

    PubMed  Article  Google Scholar 

  • 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.

    PubMed  PubMed Central  Article  Google Scholar 

  • 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.

    Article  Google Scholar 

  • Naegel, S., Holle, D., & Obermann, M. (2014b). Structural imaging in cluster headache. Current Pain and Headache Reports, 18(5), 415.

    PubMed  Article  Google Scholar 

  • 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.

    PubMed  Article  Google Scholar 

  • 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.

    PubMed  PubMed Central  Article  Google Scholar 

  • 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.

    PubMed  Article  Google Scholar 

  • 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.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • 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.

    PubMed  Article  Google Scholar 

  • 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.

    CAS  PubMed  Article  Google Scholar 

  • 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.

    PubMed  PubMed Central  Article  Google Scholar 

  • 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.

    PubMed  Article  Google Scholar 

  • 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.

    PubMed  PubMed Central  Article  Google Scholar 

  • Valfre, W., Rainero, I., Bergui, M., & Pinessi, L. (2008). Voxel-based morphometry reveals gray matter abnormalities in migraine. Headache, 48(1), 109–117.

    PubMed  Article  Google Scholar 

  • 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.

    PubMed  Article  Google Scholar 

  • 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.

    PubMed  Article  Google Scholar 

  • 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.

    PubMed  Article  Google Scholar 

  • 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.

    PubMed  PubMed Central  Article  Google Scholar 

  • 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.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

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Acknowledgements

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

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Authors

Contributions

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.

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Correspondence to Antonio Giorgio.

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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.

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Co-investigators Alberto Chiarugi (Headache Centre, Careggi University Hospital, Department of Health Sciences, University of Florence, Florence, Italy)

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Giorgio, A., Lupi, C., Zhang, J. et al. Changes in grey matter volume and functional connectivity in cluster headache versus migraine. Brain Imaging and Behavior 14, 496–504 (2020). https://doi.org/10.1007/s11682-019-00046-2

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  • DOI: https://doi.org/10.1007/s11682-019-00046-2

Keywords

  • Cluster headache
  • Migraine
  • MRI
  • Volumetry
  • Connectivity