Altered hypothalamic functional connectivity in post-traumatic headache after mild traumatic brain injury

BACKGROUND: Post-traumatic headache (PTH) is one of the most frequent symptoms following mild traumatic brain injury (mTBI). Neuroimaging studies implicate hypothalamic function connectivity (FC) disruption as an important factor in pain disorders. However, it is unknown whether there are alterations in the hypothalamus-based resting state FC within PTH following mTBI at the acute stage and its relationship with headache symptom measurement. METHODS: Forty-four mTBI patients with PTH, 27 mTBI patients without PTH and 43 healthy controls who were well matched for age, gender, and years of education were enrolled in this study. All participants underwent resting-state functional magnetic resonance imaging (fMRI) scanning as well as headache symptom measurement and cognitive assessment. Hypothalamic resting state networks were characterized by using a standard seed-based whole-brain correlation method. The bilateral hypothalamic FC was compared among the three groups. Furthermore, the correlations between hypothalamic resting state networks and headache frequency, headache intensity and MoCA scores was investigated in mTBI patients with PTH using Pearson rank correlation. RESULTS: Compared with mTBI patients without PTH, mTBI patients with PTH at the acute stage presented significantly decreased left hypothalamus-based FC with the right middle frontal gyrus (MFG) and right medial superior frontal gyrus (mSFG), and significantly decreased right hypothalamus-based FC with the right MFG. Decreased FC of the right MFG was significantly positively associated with headache frequency and headache intensity (r = 0.339, p = 0.024; r = 0.408, p = 0.006, respectively). Decreased FC of the right mSFG was significantly positively associated with headache frequency and headache intensity (r = 0.740, p < 0.0001; r = 0.655, p < 0.0001, respectively). CONCLUSION: Our data provided evidence of disrupted hypothalamic FC in patients with acute mTBI with PTH, while abnormal FC significantly correlated with headache symptom measurement. Taken together, these changes may play an essential role in the neuropathological mechanism of mTBI patients with PTH.