The missing link: Enhanced functional connectivity between amygdala and visceroceptive cortex in migraine

Background Migraine is a neurovascular disorder in which altered functional connectivity between pain-modulating circuits and the limbic system may play a role. Cortical spreading depression (CSD), which underlies migraine aura (MWA), induces C-fos expression in the amygdala. The role of CSD and amygdala connectivity in migraine without aura (MwoA) is less clear and may differentiate migraine from other chronic pain disorders. Methods Using resting-state functional MRI, we compared functional connectivity between the amygdala and the cortex in MWA and MWoA patients as well as in healthy subjects and in two other chronic pain conditions not associated with CSD: trigeminal neuralgia (TGN) and carpal tunnel syndrome (CTS). Results Amygdala connectivity in both MWA and MWoA was increased to the visceroceptive insula relative to all other groups examined. Conclusion The observed increased connectivity within the limbic/viscerosensory network, present only in migraineurs, adds to the evidence of a neurolimbic pain network dysfunction and may reflect repetitive episodes of CSD leading to the development of migraine pain.