Sleep moderates how prenatal and childhood pollutant exposure impacts white matter microstructural integrity in adolescence

Air pollution is a ubiquitous neurotoxicant linked to altered structural brain connectivity. Sleep may offer neuroprotection through its roles in brain waste clearance and immune regulation. Using Fitbit-derived sleep data and multi-shell diffusion MRI from 2178 children (ages 10-13) in the ABCD Study®, we examined whether sleep moderated associations between prenatal and childhood exposure to PM_2.5, NO₂, and O₃ and white matter microstructure. Restriction spectrum imaging yielded restricted normalized isotropic (RNI) and directional (RND) metrics, averaged across tracts. Pollution exposure was estimated at prenatal and childhood (ages 9-10) residences. Linear mixed-effects models tested sleep-by-pollution interactions on RNI/RND. Childhood NO₂ and prenatal O₃ interacted with sleep duration and efficiency, respectively, to influence RND. Among children with similar pollutant exposure, those with longer sleep duration and higher sleep efficiency had lower RND than peers with poorer sleep. This suggests that healthy sleep may buffer adverse effects of air pollution on white matter integrity.