Increased Pregenual Anterior Cingulate Cortex Activation May Contribute to Recurring Headaches

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Citalopram challenge led to increased fMRI signal in the pregenual anterior cingulate cortex in patients with migraine vs controls, which is an important area processing emotional aspects of pain.

Increased sensitivity of the right pregenual anterior cingulate cortex (pgACC) to increased brain serotonin levels is associated with recurring headaches as well as with increased stress sensitivity and emotional aspects of pain in patients with migraine, according to a pilot study published in BMC Neurology.

A total of 27 healthy controls without pain and 6 patients with migraine without aura were enrolled in the study. Participants underwent 2 pharmacologic challenge magnetic resonance imaging sessions and were administered either intravenous citalopram 7.5 mg or a normal saline placebo. A region of interest analysis was performed on the anterior cingulate cortex in an effort to compare citalopram-evoked activation changes between patients with migraine without aura and healthy controls.

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There were significant differences in anterior cingulate cortex activation between healthy controls and patients with migraine, with these differences observed in 2 peaks in the pgACC during and following citalopram infusion vs placebo. A slight difference between groups in the left pregenual region of rostral anterior cingulate cortex was observed, but this difference was not significant. Additionally, there was evidence of increased pgACC activation in patients with migraine compared with controls, according to the extracted time series. This increase was particularly pronounced in the first 8 to 10 minutes following the beginning of citalopram administration.

Limitations of this study included the small sample sizes as well as the lack of investigation into the activation differences in other pain processing areas of the whole brain.

“These observations suggest that the pgACC activation might also increase during migraine attacks,” the researchers wrote, “which process might be related to the suddenly increasing [brain serotonin] levels, contributing to the suffering element of pain.”


Edes AE, McKie S, Szabo E, et al. Increased activation of the pregenual anterior cingulate cortex to citalopram challenge in migraine: an fMRI study. BMC Neurol. 2019;19(1):237.