Disentangling the Unique Contributions of Age, Pubertal Stage, and Pubertal Hormones to White Matter Microstructure in Childhood and Adolescence

Puberty is associated with hormone level changes that influence white matter development. It remains unclear how pubertal stage and pubertal hormones uniquely relate to white matter microstructure development. Further, it is unclear if white matter tracts develop along a hierarchical sensorimotor-association (S-A) axis, similar to other aspects of brain development. We used the Human Connectome Project in Development cross-sectional sample of 1,131 youth (aged 5-21 years) to investigate unique contributions of sex, age, pubertal stage, DHEA, testosterone, estradiol, and progesterone with fractional anisotropy (FA) within canonical white matter tracts. The average S-A axis rank was calculated for tract cortical endpoints. Age was the best-fit model for 17 tracts with prefrontal, parietal, and temporal connections. The Pubertal Timing model (age-adjusted pubertal stage) was the best fit for the inferior longitudinal fasciculus. The DHEA model was the best fit for the splenium, genu, and prefrontal body of the corpus callosum. The Estradiol model was the best fit for the ventral cingulum bundle, extreme capsule, and uncinate fasciculus. The Full model was the best fit for the rostrum. The tract best fit by the Pubertal Timing model was related to sensory cortices, while the tracts best fit by hormone models were related to association cortex. Radial diffusivity explained more FA variability than axial diffusivity in all tracts, suggesting FA changes may be related to myelination. Thus, pubertal timing may be more uniquely related to white matter tract microstructure (particularly myelin) in sensory visual cortices, while pubertal hormones are more related to association-related tracts.