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Cephalalgia. 2018 Apr;38(5):846-854. doi: 10.1177/0333102417715230. Epub 2017 Jun 12.

Resting state connectivity between default mode network and insula encodes acute migraine headache.

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1 G.B. Bietti Foundation IRCCS, Research Unit of Neurophysiology of Vision and Neurophthalmology, Rome, Italy.
2 "Sapienza" University of Rome, Department of Neurology and Psychiatry, Neuroradiology section, Rome, Italy.
3 Don Carlo Gnocchi Onlus Foundation, Milan, Italy.
4 "Sapienza" University of Rome Polo Pontino, Department of Medico-surgical Sciences and Biotechnologies, Latina, Italy.
5 Università Cattolica del Sacro Cuore/CIC, Istituto di Anestesiologia, Rianimazione e Terapia del Dolore, Rome, Italy.
6 IRCCS Neuromed, Pozzilli (IS), Italy.
7 Headache Research Unit, Department of Neurology-CHR Citadelle, University of Liège, Belgium.


Background Previous functional MRI studies have revealed that ongoing clinical pain in different chronic pain syndromes is directly correlated to the connectivity strength of the resting default mode network (DMN) with the insula. Here, we investigated seed-based resting state DMN-insula connectivity during acute migraine headaches. Methods Thirteen migraine without aura patients (MI) underwent 3 T MRI scans during the initial six hours of a spontaneous migraine attack, and were compared to a group of 19 healthy volunteers (HV). We evaluated headache intensity with a visual analogue scale and collected seed-based MRI resting state data in the four core regions of the DMN: Medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC), and left and right inferior parietal lobules (IPLs), as well as in bilateral insula. Results Compared to HV, MI patients showed stronger functional connectivity between MPFC and PCC, and between MPFC and bilateral insula. During migraine attacks, the strength of MPFC-to-insula connectivity was negatively correlated with pain intensity. Conclusion We show that greater subjective intensity of pain during a migraine attack is associated with proportionally weaker DMN-insula connectivity. This is at variance with other chronic extra-cephalic pain disorders where the opposite was found, and may thus be a hallmark of acute migraine head pain.


Brain networks; insula; magnetic resonance imaging; migraine; seed-based resting state

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