Brain network functional connectivity alterations associated with acute posttraumatic headache

OBJECTIVES/BACKGROUND: To investigate disruptions in resting state networks in participants with acute posttraumatic headache (PTH) due to mild traumatic brain injury (mTBI). Neuroimaging studies have demonstrated alterations in functional connectivity (FC) within core resting-state networks in participants with headache versus healthy controls (HCs), which may provide insights into disease mechanisms; however, the extent to which these alterations relate to PTH remains incompletely understood. METHODS: In this comparative cross-sectional study with an embedded prospective cohort, participants with acute PTH and HCs were enrolled from the Mayo Clinic Arizona and Minnesota, and the Phoenix Veterans Affairs Health Care between 2020 and 2024. Participants with PTH underwent resting-state magnetic resonance imaging within 2 months following mTBI. We investigated differences within and between functional brain networks in participants with PTH compared to HCs. Associations between altered FC with headache frequency, alterations of mood, post-mTBI symptoms, and concussion history were determined and corrected for age and sex. Relationships between PTH outcomes at 3 months and baseline FC were investigated. RESULTS: Ninety-six participants with acute PTH (35 male, 61 female) and 84 age-balanced HCs were included. Decreased resting state network connectivity in participants with PTH compared to HCs (False Discovery Rate (FDR) corrected <0.05) was observed in two default mode network (DMN) regions encompassing the bilateral frontal and anterior cingulate cortex (ACC), as well as the left postcentral gyrus. Within those DMN regions, exploratory analyses revealed that FC was positively associated with headache frequency in the bilateral ACC, right precuneus and frontal gyrus, and with trait anxiety in the right ACC. In contrast, negative associations were observed between FC and number of mTBIs, as well as state anxiety, in the left ACC (uncorrected, p<0.05). No significant associations with clinical headache variables were observed in the DMN comprising the left postcentral gyrus. Baseline group differences in network connectivity between recovered and nonrecovered participants were found in visual, sensorimotor, default mode, executive control and salience networks. Alterations in baseline connectivity between independent components in recovered and nonrecovered participants were not statistically significant after corrections for multiple comparisons. CONCLUSION: In participants with PTH, the DMN regions showing decreased connectivity also exhibited associations with headache frequency, state and trait anxiety, and number of lifetime mTBIs, suggesting that these changes relate to the severity and persistence of post-mTBI symptoms. The baseline differences in network connectivity between recovered and nonrecovered participants were not statistically significant after corrections for multiple comparisons, indicating that baseline network connections may not play a significant role in the recovery process.