The proposed study will address the hypothesis that exposure to traffic-related air pollution (TRAP) during critical periods of brain development is significantly associated with altered neurobehavior including deficits in cognition, attention, memory, executive function, global intelligence, neuromotor function, behavioral regulation, and altered brain anatomy and physiology. Exposure to environmental neurotoxicants prenatally and during early childhood has been associated with neurobehavioral deficits and altered brain structure. Recent toxicological evidence suggests that TRAP, a complex mixture of metals, elemental and organic carbon, polycyclic aromatic hydrocarbons, and fine and ultrafine particulate matter, is capable of inducing neuroinflammation and translocation across the blood-brain barrier resulting in direct exposure to the brain. The aims of this study are to determine if children exposed to increased levels of TRAP during early stages of brain development have neurobehavioral deficits in childhood and to assess the physiologic impact of TRAP exposure on brain structure, organization, and function. The Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS), a prospective cohort study, provides an extraordinary opportunity to accomplish these aims. The CCAAPS cohort was recruited to examine the association between traffic exhaust and the development of allergic disease and asthma. Children enrolled in CCAAPS must have resided either less than 400 m or greater than 1500 m from a major highway at the time of their birth. TRAP exposure during early childhood has been characterized using ambient air monitoring and spatial models. Clinical health assessments, biomarkers, health questionnaires, and addresses of all home, daycare, and school locations have been collected at ages 1-4 and 7. The proposed study is innovative as it exploits all of the collected health, air monitoring, and modeling data and extends the focus of the CCAAPS cohort to examine the impact of early childhood TRAP exposure on neurobehavior and neuroimaging outcomes. A carefully selected battery of valid and reliable tests will be administered at age 11-12 to assess neurobehavioral development. Another unique aspect is the proposed nested study of children with high and low exposure to TRAP during early childhood to assess the physiologic impact of TRAP on the developing brain using quantitative magnetic resonance imaging (MRI). The anticipated results will address a significant gap in scientific knowledge of the potential neurotoxicity of a ubiquitous environmental exposure with far-reaching consequences for future studies and public health. ExpandCollapse Abstract