Increased activation of the pregenual anterior cingulate cortex to citalopram challenge in migraine: an fMRI study
Andrea Edit Edes,
Shane McKie,
Edina Szabo,
Gyongyi Kokonyei,
Dorottya Pap,
Terezia Zsombok,
Mate Magyar,
Eva Csepany,
Gabor Hullam,
Adam Gyorgy Szabo,
Lajos Rudolf Kozak,
Gyorgy Bagdy,
Gabriella Juhasz
Affiliations
Andrea Edit Edes
SE-NAP2 Genetic Brain Imaging Migraine Research Group, Semmelweis University
Shane McKie
Faculty of Biological, Medical and Human Sciences Platform Sciences, Enabling Technologies and Infrastructure, Faculty of Biological, Medical and Human Sciences Research and Innovation, The University of Manchester and Manchester Academic Health Sciences Centre
Edina Szabo
SE-NAP2 Genetic Brain Imaging Migraine Research Group, Semmelweis University
Gyongyi Kokonyei
SE-NAP2 Genetic Brain Imaging Migraine Research Group, Semmelweis University
Dorottya Pap
Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University
Terezia Zsombok
Department of Neurology, Faculty of Medicine, Semmelweis University
Mate Magyar
Department of Neurology, Faculty of Medicine, Semmelweis University
Eva Csepany
Department of Neurology, Faculty of Medicine, Semmelweis University
Gabor Hullam
Department of Measurement and Information Systems, Budapest University of Technology and Economics, Faculty of Electrical Engineering and Informatics
Adam Gyorgy Szabo
MR Research Center, Semmelweis University
Lajos Rudolf Kozak
MR Research Center, Semmelweis University
Gyorgy Bagdy
Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University
Gabriella Juhasz
SE-NAP2 Genetic Brain Imaging Migraine Research Group, Semmelweis University
Abstract Background The anterior cingulate cortex (ACC) is a key structure of the pain processing network. Several structural and functional alterations of this brain area have been found in migraine. In addition, altered serotonergic neurotransmission has been repeatedly implicated in the pathophysiology of migraine, although the exact mechanism is not known. Thus, our aim was to investigate the relationship between acute increase of brain serotonin (5-HT) level and the activation changes of the ACC using pharmacological challenge MRI (phMRI) in migraine patients and healthy controls. Methods Twenty-seven pain-free healthy controls and six migraine without aura patients participated in the study. All participant attended to two phMRI sessions during which intravenous citalopram, a selective serotonin reuptake inhibitor (SSRI), or placebo (normal saline) was administered. We used region of interest analysis of ACC to compere the citalopram evoked activation changes of this area between patients and healthy participants. Results Significant difference in ACC activation was found between control and patient groups in the right pregenual ACC (pgACC) during and after citalopram infusion compared to placebo. The extracted time-series showed that pgACC activation increased in migraine patients compared to controls, especially in the first 8–10 min of citalopram infusion. Conclusions Our results demonstrate that a small increase in 5-HT levels can lead to increased phMRI signal in the pregenual part of the ACC that is involved in processing emotional aspects of pain. This increased sensitivity of the pgACC to increased 5-HT in migraine may contribute to recurring headache attacks and increased stress-sensitivity in migraine.
