Fine particulate matter (aerodynamic diameter<2.5 ?m; PM2.5) is a novel and ubiquitous environmental neurotoxin affecting neurobehavioral development of millions of American children living in urban areas. However, our review points to several major methodological limitations and critical knowledge gaps in the extant literature, including: 1) the lack of studies with longitudinal brain and behavior assessments; 2) relatively small samples from localized geographical areas; 3) little to no information on long-term cumulative and/or differential timing of exposure across development; and 4) remaining questions regarding the neurotoxicity of PM2.5 exposure on critical neurobehavioral processes that continue to mature across adolescence. Although animal neurotoxicology studies have highlighted the importance of sex, there is only limited epidemiologic evidence for sex difference in PM2.5 neurotoxicity in children. Moreover, brain development is also shaped by family- and community-level social factors, but whether and how air pollution neurotoxicity interacts with the social context remains unclear. This application will leverage the nationwide longitudinal Development (ABCD) study of 9- and 10-year-olds (N=11,873) Adolescent Brain Cognitive to examine prenatal and childhood air pollution exposure effects on neurobehavioral development in boys and girls across 21 U.S. cities. ABCD outcome measures are anchored on the transition to early adolescence because neuromaturation continues from childhood through early adulthood, making such developmental transition periods potentially more vulnerable to environmental insults. Our primary exposure of interest is PM2.5, but advances in well-validated spatiotemporal modeling tools will also allow us to explore neurotoxicity of PM composition and other gaseous pollutants (i.e. NO2, O3). Given the reconstructed exposure histories from gestation to childhood to early-adolescence, we will: (a) determine long-term cumulative exposure effects; and (b) examine differential exposure effects across sensitive time windows to better define PM2.5 neurotoxicity on executive functioning (EF) and emotional behaviors from ages 9 to 12 years-old (Aim 1); and also understand how the resulting neurotoxicity influences structural and functional brain development, including brain morphology, white matter microstructure, brain activity at rest and during EF and emotion-focused tasks, and functional connectivity of large-scale networks (Aim 2).
In Aim 3, we will evaluate if children are more susceptible to PM2.5 effects based on: a) sex and SES; and b) family- and neighborhood-level contextual risk and protective factors. This application will advance our understanding of air pollution neurotoxicity on adolescent brains, as well as how exposure effects may vary across sensitive time windows of development and/or differ by individual susceptibility. The resulting new knowledge will contribute to sciences-based air pollution regulations to protect public health, but also inform the development of preventions and interventions targeting sensitive time-windows and vulnerable populations.

Public Health Relevance

Recent findings suggest that air pollution exposure during prenatal and childhood development may be a neurotoxicant; yet questions remain as to when and how the timing of exposure impacts changes in brain structure and function across diverse populations of children. The proposed study aims to determine whether long-term and/or specific periods of exposure to air pollution, with a primary focus on fine particle matter (PM2.5), alters neurocognitive abilities of executive functions, emotional behaviors, and brain development in a large, representative nationwide cohort of youth between the ages of 9 to 12 years-old. This study has the potential to improve prevention and intervention programs to reduce cognitive and emotional problems that may otherwise persist into adult life, and its findings of how air pollution impacts brain-behavior development is important to policy markers charged with regulating air quality in urban cities.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Gray, Kimberly A
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University of Southern California
Public Health & Prev Medicine
Schools of Medicine
Los Angeles
United States
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