RESUMEN
BACKGROUND: Prenatal exposure to air pollution disrupts cognitive, emotional, and behavioral development. The brain disturbances associated with prenatal air pollution are largely unknown. METHODS: In this prospective cohort study, we estimated prenatal exposures to fine particulate matter (PM2.5 ) and polycyclic aromatic hydrocarbons (PAH), and then assessed their associations with measures of brain anatomy, tissue microstructure, neurometabolites, and blood flow in 332 youth, 6-14 years old. We then assessed how those brain disturbances were associated with measures of intelligence, ADHD and anxiety symptoms, and socialization. RESULTS: Both exposures were associated with thinning of dorsal parietal cortices and thickening of postero-inferior and mesial wall cortices. They were associated with smaller white matter volumes, reduced organization in white matter of the internal capsule and frontal lobe, higher metabolite concentrations in frontal cortex, reduced cortical blood flow, and greater microstructural organization in subcortical gray matter nuclei. Associations were stronger for PM2.5 in boys and PAH in girls. Youth with low exposure accounted for most significant associations of ADHD, anxiety, socialization, and intelligence measures with cortical thickness and white matter volumes, whereas it appears that high exposures generally disrupted these neurotypical brain-behavior associations, likely because strong exposure-related effects increased the variances of these brain measures. CONCLUSIONS: The commonality of effects across exposures suggests PM2.5 and PAH disrupt brain development through one or more common molecular pathways, such as inflammation or oxidative stress. Progressively higher exposures were associated with greater disruptions in local volumes, tissue organization, metabolite concentrations, and blood flow throughout cortical and subcortical brain regions and the white matter pathways interconnecting them. Together these affected regions comprise cortico-striato-thalamo-cortical circuits, which support the regulation of thought, emotion, and behavior.