ArticleThe journal of headache and pain2026
Normative structural MRI deviation factors summarize patient-level neuroanatomical heterogeneity across episodic and chronic migraine.
Article in The journal of headache and pain, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundStructural MRI findings in migraine are inconsistent across cohorts, suggesting that group contrasts may obscure patient-level heterogeneity. We tested whether individualized normative structural deviations could be summarized into interpretable patient-level factor-weight dimensions related to chronicity and clinical burden.
methodsIn this single-center cross-sectional study, 249 adults with ICHD-3 migraine (198 episodic, 51 chronic) and 57 local healthy controls underwent 3.0-T MRI. Released PCNtoolkit lifespan models were locally adapted with controls to estimate patient-level deviation z scores for 158 FreeSurfer features. Non-negative matrix factorization was applied to the absolute-deviation matrix; directional negative- and positive-deviation models were sensitivity analyses. Covariate-adjusted associations were FDR-corrected within prespecified families.
resultThe primary model identified two stable factor-weight dimensions. Factor 1 captured a subcortical-limbic-brainstem/global-volume deviation pattern and was associated with chronic migraine (OR per 1-SD, 1.50; q = 0.036), MIDAS (beta = 16.46; q = 0.007), and monthly headache days (beta = 9.41; q < 0.001). Factor 2 mainly reflected cortical-thickness deviations, showed a borderline inverse association with chronic migraine (OR = 0.68; q = 0.054), and was associated with high absolute-deviation burden (OR = 2.37; q < 0.001). HIT-6 showed no corrected factor-specific association. Removing cranial-size-sensitive features preserved factor structure and main Factor 1 associations.
conclusionNormative structural MRI deviations in migraine can be summarized into non-mutually exclusive deviation-burden factors with patient-level weights. Factor 1 showed the most consistent associations with chronic migraine, headache frequency, and MIDAS; these associations attenuated in restricted sensitivity analyses, and external validation is required before clinical application.
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