Urban air pollution and neurobehavioral trajectories in the ABCD study

项目摘要 细颗粒物（空气动力学直径<2.5 μm; PM2.5）是一种新的、普遍存在的环境污染物 神经毒素影响数百万生活在城市地区的美国儿童的神经行为发育。 然而，我们的评论指出了几个主要的方法限制和关键的知识差距，在现存的 文献，包括：1）缺乏纵向大脑和行为评估的研究; 2）相对较小 来自局部地理区域的样本; 3）关于长期累积和/或差异的信息很少或没有 整个发展过程中暴露的时间;以及4）关于PM2.5神经毒性的剩余问题 暴露在关键的神经行为过程中，这些过程在青春期继续成熟。虽然动物 神经毒理学研究强调了性的重要性，只有有限的流行病学证据， 儿童PM2.5神经毒性的性别差异此外，大脑发育也受到家庭的影响， 社区层面的社会因素，但空气污染神经毒性是否以及如何与社会背景相互作用 仍不清楚该应用程序将利用全国纵向 9岁和10岁儿童的发育（ABCD）研究（N= 11，873） 青少年大脑认知 检查产前和儿童期的空气污染 暴露对美国21个城市男孩和女孩神经行为发育的影响。ABCD结局 这些措施都是建立在向青春期早期过渡的基础上的，因为神经成熟从 儿童期到成年早期，使这种发育过渡期可能更容易受到 环境侮辱。我们感兴趣的主要暴露是PM2.5，但在经过充分验证的时空 建模工具还将使我们能够探索PM组合物和其他气态污染物的神经毒性（即， NO2、O3）。考虑到从妊娠期到儿童期到青春期早期的重建暴露历史，我们将： (a)确定长期累积暴露效应;和（B）检查不同暴露效应 敏感的时间窗口，以更好地定义PM2.5对执行功能（EF）和情绪的神经毒性 行为从9岁到12岁（目标1）;并了解如何产生神经毒性影响 脑结构和功能发育，包括脑形态学、白色物质显微结构、脑 在休息和EF和情绪为重点的任务期间的活动，以及大规模网络的功能连接 (Aim 2）。在目标3中，我们将评估儿童是否更容易受到PM2.5的影响：a）性别和社会经济地位; 和B）家庭和邻里水平的背景风险和保护因素。这一应用将推动我们的 了解空气污染对青少年大脑的神经毒性，以及暴露影响如何变化 跨越发育的敏感时间窗和/或因个体易感性而不同。由此产生的新 知识将有助于以科学为基础的空气污染法规，以保护公众健康，但也告知 制定针对敏感时间窗口和弱势群体的预防和干预措施。

Project Summary Fine particulate matter (aerodynamic diameter<2.5 μm; 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.