Air Pollution, Multidimensional Behavior, and Neuroimaging in Children with Neurodevelopmental Disorders

空气污染、多维行为和神经发育障碍儿童的神经影像学

基本信息

批准号：
10644622
负责人：
Elza Rechtman
金额：
$ 9.79万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-12 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10644622
关键词：
Address Adolescent Adopted Air Pollution Area Attention Attention deficit hyperactivity disorder Behavior Behavioral Behavioral Mechanisms Big Data Biometry Brain Characteristics Chemicals Child Childhood Climate Complex Data Data Science Data Set Development Diagnosis Diagnostic Dimensions Disease Eligibility Determination Environment Environmental Exposure Environmental Impact Environmental Risk Factor Epidemiologist Epidemiology Exposure to Faculty Foundations Functional disorder Future Goals Grant Health Heritability Human Individual Intervention Label Lead Life Life Style Link Literature MRI Scans Magnetic Resonance Imaging Measures Mentors Mentorship Methods Modeling National Institute of Environmental Health Sciences Nested Case-Control Study Neurobiology Neurodevelopmental Disorder Neurosciences New York City Organizational Models Outcome Participant Particulate Matter Phase Phenotype Population Populations at Risk Positioning Attribute Prediction of Response to Therapy Predisposition Pregnancy Prevalence Prevention Preventive Process Recording of previous events Reproducibility Research Research Personnel Resolution Resources Risk Sampling Series Signal Transduction Social outcome Strategic Planning Stress Structure Sum Technical Expertise Time Training Transcend Writing autism spectrum disorder autistic children behavioral outcome behavioral phenotyping biobank career career networking climate change climate crisis climate-related exposures clinical decision-making comorbidity diagnostic strategy environmental chemical fine particles follow-up gene environment interaction high dimensionality image archival system interest member meter multimodality neural neurobiological mechanism neurodevelopment neuroimaging neuromechanism neurotoxic novel phenotypic data prenatal prenatal exposure repository skill acquisition skills training social spatiotemporal temporal measurement tenure track

项目摘要

PROJECT SUMMARY I am a dually trained neuroscientist and environmental epidemiologist. My primary research interest is the impact of early life environmental exposures on the developing brain. The goal of this proposal is to gain training in biostatistics, epidemiology, and data science, supporting my transition into an independent transdisciplinary researcher in the emerging field of big-data environmental developmental neuroscience. I propose a novel application of the lagged weighted quantile sum (LWQS) regression to link temporally resolved air pollution (particulate matter < 2.5 µm; PM2.5) with diagnostic and transdiagnostic (multi-dimensional behavioral and neural changes) in children with autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). I leverage rich, existent behavioral and magnetic resonance imaging (MRI) phenotyping from a well-established big-data biobank, the Healthy Brain Network (HBN), along with a novel spatiotemporal model of weekly PM2.5 exposure. I hypothesize that higher PM2.5 exposure during critical windows of prenatal development is associated with increased ASD and ADHD diagnosis, and a transdiagnostic approach captures the population burden of exposure. In the K99 phase, I propose to uncover mechanistic links between prenatal ambient PM2.5 exposure and behavioral (Aim 1) and MRI (Aim 2) phenotypes in children with ASD and ADHD. In the R00 phase, I propose to acquire longitudinal behavioral and MRI data to examine associations between prenatal PM2.5 exposure on developmental trajectories (Aim 3). To achieve these scientific goals, I will obtain training and mentorship from an expert mentoring team with transdisciplinary expertise which will provide me with balanced training in both technical skills, and professional development. Technical skills will cover: 1) high dimensional longitudinal analytic approaches with Dr. Chris Gennings, 2) environmental developmental epidemiology with Dr. Megan Horton, and 3) processing of big-data MRI and behavioral datasets with Dr. Mike Milham. Dr. Horton will also lead my professional development skills training, including grant writing, project management, strategic planning to accomplish short- and long- term goals, maintaining scientific rigor and reproducibility, and cultivating a professional network. The proposed complementary training plan positions me to pioneer the use of big data to investigate the link between multidimensional exposures and behavioral and neuroimaging outcomes in typically and atypically developing children. My long-term career goal is to use big data to assess the impact of the changing climate on children’s brain and behavioral outcomes. I will use this K99/R00 as a foundation for a future R01 grant and career as an independent tenure-track faculty member. This application overcomes barriers in environmental developmental neuroscience thus advancing our ability to identify mechanisms underlying associations between climate- related environmental exposures and neurodevelopmental disorders.

项目摘要我是一名受训练的神经科学家和环境流行病学家。我的主要研究兴趣是早期生活环境暴露对发展中的大脑的影响。该提议的目的是获取生物统计学，流行病学和数据科学培训，支持我向独立的过渡大数据环境发展神经科学新兴领域的跨学科研究人员。我提案滞后的加权分位数总和（LWQ）回归以暂时链接的新颖应用已解决的空气污染（颗粒物<2.5 µm; pm2.5）具有诊断和转诊（多维）自闭症谱系障碍（ASD）和注意力不足儿童的行为和神经变化）多动症（ADHD）。我利用丰富的，现有的行为和磁共振成像（MRI）来自公认的大数据生物库，健康脑网络（HBN）的表型以及一种新颖每周PM2.5暴露的时空模型。我假设在关键期间，较高的PM2.5暴露产前开发的窗口与增加的ASD和ADHD诊断有关，以及转诊方法捕获了暴露的人口负担。在K99阶段，我建议揭露产前环境PM2.5暴露与行为（AIM 1）和MRI（AIM 2）之间的机械联系（AIM 2） ASD和ADHD儿童的表型。在R00阶段，我建议获得纵向行为和MRI数据以检查产前PM2.5发育轨迹之间的关联（AIM 3）。为了实现这些科学目标，我将从专家心态团队中获得培训和心理跨学科专业知识将为我提供技术技能和专业的平衡培训发展。技术技能将涵盖：1）与克里斯博士一起使用的高维纵向分析方法 Gennings，2）与Megan Horton博士的环境发展流行病学，3）大数据处理 MRI和行为数据集与Mike Milham博士。霍顿博士还将领导我的专业发展技能培训，包括赠款写作，项目管理，战略计划，以完成短期和长期定期目标，维持科学严格和可重复性，并培养专业网络。提议完全训练计划使我在使用大数据来研究多维暴露以及典型和非典型发展中的行为和神经影像成果孩子们。我的长期职业目标是使用大数据来评估不断变化的气候对儿童的影响大脑和行为结果。我将使用此K99/R00作为未来R01赠款和职业的基础独立的终身教师。该应用程序克服了环境发展的障碍神经科学因此促进了我们确定气候之间关联机制的能力 - 相关的环境暴露和神经发育障碍。