The Journal of Headache and Pain (Jul 2025)

White matter tract differences in persistent post-traumatic headache, migraine, and healthy controls: a diffusion tensor imaging study

  • Rune Häckert Christensen,
  • Haidar Muhsen Al-Khazali,
  • Cédric Gollion,
  • Basit Ali Chaudhry,
  • Messoud Ashina,
  • Håkan Ashina

DOI
https://doi.org/10.1186/s10194-025-02084-2
Journal volume & issue
Vol. 26, no. 1
pp. 1 – 10

Abstract

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Abstract Background Persistent post-traumatic headache (PPTH) frequently resembles migraine but may involve distinct white matter perturbations. We compared white matter fiber tracts among adults with PPTH, migraine, and healthy controls (HCs). Methods This cross-sectional diffusion tensor imaging (DTI) study enrolled adults with PPTH, migraine, and HCs, who underwent a single 3T MRI session. Tract-based spatial statistics quantified white matter integrity. Outcome measures included fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity, and radial diffusivity. Group comparisons used general linear models with threshold-free cluster enhancement and 5,000 permutations. Voxelwise significance was set at P < 0.05 after family-wise error correction, adjusting for age and sex. Post-hoc region-of-interest (ROI) analyses explored differences within significant regions. Results Imaging data were available from 100 participants with PPTH, 293 with migraine, and 154 HCs. Compared to participants with migraine, those with PPTH exhibited higher FA and AD values in the posterior limb of the internal capsule and superior corona radiata (P FWE < 0.05), findings that were further confirmed by post-hoc ROI analysis relative to HCs (both P < 0.001). FA values within these tracts were positively associated with monthly migraine-like headache days (β = 0.00045; P = 0.043). In addition, participants with PPTH showed lower AD values within the corpus callosum compared to those with migraine (P FWE < 0.05), with post-hoc ROI analyses also demonstrating similar differences relative to HCs (P = 0.002). Lower corpus callosal AD values were associated with greater post-concussive symptom severity (β = − 0.0000013; P = 0.036). Mean diffusivity and radial diffusivity did not differ among groups. Conclusions PPTH is associated with distinct white matter alterations involving ascending somatosensory pathways and interhemispheric fibers. These alterations are associated with clinical symptom severity and differentiate adults with PPTH from those with migraine, suggesting trauma-induced maladaptive plasticity.