Sex-specific orchestration of morphometric similarity networks in children and adolescents with migraine

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Abstract
Background: Migraine accounts for most primary headaches in children and adolescents and is related to cortical and connectivity changes. However, the underlying mechanisms remain unclear. Morphometric similarity mapping has not yet been applied to children and adolescents with migraine. Methods: Eighty-three patients (6–17 years) with migraine without aura and 81 age- and sex-matched controls were retrospectively included. High-resolution 3D T1-weighted and diffusion-weighted magnetic resonance imaging scans were processed to extract cortical morphometric parameters and compute morphometric similarity networks (MSN). Global and regional MSN differences were assessed between patients and controls, and across subgroups defined by sex, attack frequency and migraine-associated symptoms. Results: Patients showed significant MSN alterations, particularly in temporal and cingulate regions. Sex emerged as the strongest factor influencing MSN architecture, with additional modulations linked to attack frequency and clinical symptoms. Affected pathways encompassed the executive control, nociceptive and default mode networks. Conclusions: Migraine in children and adolescents is associated with widespread MSN abnormalities, likely reflecting cortical reorganization mechanisms. Male and female patients appear to engage distinct neural “orchestras”, each emphasizing different network sections (sensory–affective in males and cognitive–attentive in females) to produce a shared clinical experience. These findings highlight sex as a key determinant of migraine neurobiology in developmental age.
Funding Information
  • the IHS Research into Headache in Children and Adolescents Seed
  • Ministero della Salute (Current Research)

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