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


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.


Cluster headache Migraine MRI Volumetry Connectivity 



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.


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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

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