OBJECTIVE: To investigate resting-state functional connectivity in the salience network (SN), the sensorimotor network (SMN), and the default mode network (DMN) during migraine attacks induced by pituitary adenylate cyclase-activating polypeptide-38 (PACAP38).

METHODS: In a double-blind, randomized study, 24 female migraine patients without aura received IV PACAP38 or vasoactive intestinal polypeptide (VIP) over 20 minutes. Both peptides are closely related and cause vasodilation, but only PACAP38 induces migraine attacks. VIP was therefore used as active placebo. Resting-state functional MRI was recorded before and during PACAP38-induced migraine attacks and before and after VIP infusion. We analyzed data by Statistical Parametric Mapping 8 and the Resting-State fMRI Data Analysis Toolkit for Matlab in a seed-based fashion.

RESULTS: PACAP38 (n = 16) induced migraine attacks and increased connectivity with the bilateral opercular part of the inferior frontal gyrus in the SN. In SMN, there was increased connectivity with the right premotor cortex and decreased connectivity with the left visual cortex. Several areas showed increased (left primary auditory, secondary somatosensory, premotor, and visual cortices) and decreased (right cerebellum and left frontal lobe) connectivity with DMN. We found no resting-state network changes after VIP (n = 15).

CONCLUSIONS: PACAP38-induced migraine attack is associated with altered connectivity of several large-scale functional networks of the brain.