Increased Activation of the Pregenual Anterior Cingulate Cortex to Citalopram Challenge in Migraine: An fMRI Study

BMC Neurol. 2019 Oct 15;19(1):237. doi: 10.1186/s12883-019-1478-0.


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.

Keywords: Anterior cingulate cortex; Citalopram; Migraine without aura; Pharmacological challenge MRI.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Brain Mapping / methods
  • Citalopram / pharmacology
  • Double-Blind Method
  • Female
  • Gyrus Cinguli / drug effects
  • Gyrus Cinguli / metabolism*
  • Gyrus Cinguli / physiopathology*
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Migraine Disorders / metabolism*
  • Migraine Disorders / physiopathology*
  • Serotonin / metabolism*
  • Serotonin Uptake Inhibitors / pharmacology


  • Serotonin Uptake Inhibitors
  • Citalopram
  • Serotonin