Regional Organisation and Sex-Related Differences in Trigeminal Nerve DTI Metrics in Healthy Young Adults

Trigeminal neuralgia has been associated with microstructural alterations of the trigeminal nerve, particularly at the root entry zone, but region-specific reference data stratified by sex in healthy individuals are lacking. This study aimed to characterise the regional organisation of the trigeminal nerve using diffusion tensor imaging (DTI) metrics and volumetry in healthy young adults, describing regional heterogeneity, lateral asymmetry and sex effects. T1-weighted and diffusion-weighted images from 300 Human Connectome Project participants (150 women, 150 men; 22-35 years) were used to bilaterally segment four regions of the trigeminal nerve. For each region of interest, we derived absolute and relative volumes, fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity, computed asymmetry indices and coefficients of variation, and applied t-tests, MANOVA and effect sizes to assess regional, lateral and sex-related differences. We observed a pronounced regional gradient in fractional anisotropy, with highest values at the root entry zone and a progressive decrease towards Meckel's cave. Lateral asymmetries were generally small, and sex systematically influenced diffusion metrics and volumes in specific regions of interest, while preserving the same spatial pattern along the nerve. In healthy young adults, the trigeminal nerve exhibits a marked regional gradient in fractional anisotropy, accompanied by modest physiological lateral asymmetry and consistent sex-related differences. These findings establish region- and sex-specific reference ranges for diffusion metrics and volumes of the trigeminal nerve, providing a quantitative framework to distinguish expected variability from disease-compatible alterations in future studies.