Post-traumatic headache (PTH) is a common consequence of mild traumatic brain injury (mTBI), significantly impacting an individual's quality of life and rehabilitation. However, the underlying neuropathogenesis of PTH remains poorly understood. This study utilized diffusion tensor imaging (DTI) to detect microstructural brain alterations in mTBI participants with or at risk of developing PTH. The current study investigated associations between early DTI metrics (1-month postinjury), pain sensitivity (quantitative sensory tests), and psychological assessments (1-month and 6-months postinjury) to identify differences between mTBI (n=12) and healthy controls (HC; n=10). Abnormalities in mean axial diffusivity in the forceps major were observed in mTBI relative to HCs at 1-month postinjury (p=0.02). Within the mTBI group, DTI metrics at 1-month postinjury were significantly associated (p<0.05) with pain-related measures and psychological outcomes at 6-months postinjury. Notably, the associations between early DTI metrics and later pain-related measures exhibited significant group differences in right sagittal stratum (p<0.01), white matter tract in left insula (p<0.04), and left superior longitudinal fasciculus (p<0.05). In conclusion, these findings indicate that DTI metrics can be used to predict pain and psychological measures in mTBI, suggesting an important role of white matter microstructure in PTH following mTBI.

The authors have declared no competing interest.

This study is supported by funding from the Indiana Clinical and Translational 401 Sciences Institute, which is funded in part by UL1TR002529 (FAW KMN YCW), U.S. Army 402 Medical Research and Development Command (W81XWH-18-1-0433 and W81XWH-18-1- 403 0434 to FAW and KMN) and National Institutes of Health (R01 NS102415 to FAW and R01 404 NS112303 to YCW).

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The studies involving humans were approved by Indiana University Institutional review board (IUIRB). The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. No potentially identifiable images or data are presented in this study.

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