Introduction Although migraine and persistent post-traumatic headache often share phenotypic characteristics, few studies have interrogated the pathophysiological differences underlying these headache types. While there is now some indication of differences in brain structure between migraine and persistent post-traumatic headache, differences in brain function have not been adequately investigated. The objective of this study was to compare static and dynamic functional connectivity patterns in migraine versus persistent post-traumatic headache using resting-state magnetic resonance imaging. Methods This case-control study interrogated the static functional connectivity and dynamic functional connectivity patterns of 59 a priori selected regions of interest involved in pain processing. Pairwise connectivity (region of interest to region of interest) differences between migraine (n = 33) and persistent post-traumatic headache (n = 44) were determined and compared to healthy controls (n = 36) with ANOVA and subsequent t-tests. Pearson partial correlations were used to explore the relationship between headache burden (headache frequency; years lived with headache) and functional connectivity and between pain intensity at the time of imaging and functional connectivity for migraine and persistent post-traumatic headache groups, separately. Results Significant differences in static functional connectivity between migraine and persistent post-traumatic headache were found for 17 region pairs that included the following regions of interest: Primary somatosensory, secondary somatosensory, posterior insula, hypothalamus, anterior cingulate, middle cingulate, temporal pole, supramarginal gyrus, superior parietal, middle occipital, lingual gyrus, pulvinar, precuneus, cuneus, somatomotor, ventromedial prefrontal cortex, and dorsolateral prefrontal cortex. Significant differences in dynamic functional connectivity between migraine and persistent post-traumatic headache were found for 10 region pairs that included the following regions of interest: Secondary somatosensory, hypothalamus, middle cingulate, temporal pole, supramarginal gyrus, superior parietal, lingual gyrus, somatomotor, precentral, posterior cingulate, middle frontal, fusiform gyrus, parieto-occiptal, and amygdala. Although there was overlap among the regions demonstrating static functional connectivity differences and those showing dynamic functional connectivity differences between persistent post-traumatic headache and migraine, there was no overlap in the region pair functional connections. After controlling for sex and age, there were significant correlations between years lived with headache with static functional connectivity of the right dorsolateral prefrontal cortex with the right ventromedial prefrontal cortex in the migraine group and with static functional connectivity of right primary somatosensory with left supramarginal gyrus in the persistent post-traumatic headache group. There were significant correlations between headache frequency with static functional connectivity of left secondary somatosensory with right cuneus in the migraine group and with static functional connectivity of left middle cingulate with right pulvinar and right posterior insula with left hypothalamus in the persistent post-traumatic headache group. Dynamic functional connectivity was significantly correlated with headache frequency, after controlling for sex and age, in the persistent post-traumatic headache group for one region pair (right middle cingulate with right supramarginal gyrus). Dynamic functional connectivity was correlated with pain intensity at the time of imaging for the migraine cohort for one region pair (right posterior cingulate with right amygdala). Conclusions Resting-state functional imaging revealed static functional connectivity and dynamic functional connectivity differences between migraine and persistent post-traumatic headache for regions involved in pain processing. These differences in functional connectivity might be indicative of distinctive pathophysiology associated with migraine versus persistent post-traumatic headache.
