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Chemical Mixture Exposures in Early Life: Impacts on Executive Function and Neural Circuitry Across Adolescence

Award Number: R01ES038499
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/22/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2031

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Chemical Mixture Exposures in Early Life: Impacts on Executive Function and Neural Circuitry Across Adolescence - ABSTRACT Environmental exposures during early development are critical determinants of brain and behavioral outcomes. Prenatal and early childhood periods are particularly vulnerable to toxic exposures, yet most environmental neurotoxicity research is constrained by the challenges of capturing accurate early-life exposure data and linking it to long-term neurodevelopmental outcomes. Traditional prospective birth cohort studies require decades to span from in utero exposure to adolescent outcomes and often rely on maternal biomarkers with limited reliability as proxies for fetal exposure. We address these barriers by leveraging a novel biomarker— naturally shed deciduous teeth—which provides precise, time-resolved measures of in utero and early childhood chemical exposures. We combine this innovate tool with rich longitudinal neuroimaging and neuropsychological data from the ongoing Adolescent Brain Cognitive Development (ABCD) study (~10,000 participants), allowing us to investigate the impact of early-life environmental mixtures on executive function (EF) and brain development across adolescence within a 5-year study window. Our central hypothesis is that specific early life developmental windows exist during which chemical exposures, including metals and organic pollutants, alter trajectories of executive function and the underlying neural circuitry. The first aim is to identify developmental windows during which exposure to chemical mixtures impacts EF domains including attention, working memory, and cognitive flexibility. The second aim is to determine whether these exposures are associated with altered development of EF-related brain regions, including the prefrontal cortex, anterior cingulate, hippocampus, and basal ganglia. In an exploratory third aim, we will assess whether changes in brain-based phenotypes mediate the relationship between early-life exposures and EF outcomes using causal modeling approaches. This study is innovative in its integration of time-resolved exposure biomarkers with prospective, multimodal neurodevelopmental data. Our approach employs advanced statistical methods, including lagged weighted quantile sum (L-WQS) regression, to model exposure timing and mixture effects. The findings will identify critical periods of vulnerability, inform public health strategies for early-life exposure reduction, and guide future interventions aimed at improving cognitive and neural outcomes in youth.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $815,546 )
2026	2026	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Environmental Health	000	1	6/23/2026	NEW	$815,546
														Subtotal = $815,546

Grand Total All Awards = $815,546

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Chemical Mixture Exposures in Early Life: Impacts on Executive Function and Neural Circuitry Across Adolescence

Award Number: R01ES038499

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/22/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2031

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