MR assessment of brain function altered by lead exposure

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DESCRIPTION (provided by applicant) Exposure to lead during pregnancy, infancy, and childhood increases the individual likelihood of impaired school performance, increased impulsiveness, aggression, and delinquent behavior. Disorders that result from exposure to environmental neurotoxicants are a complex web of interactions between genetic, neurochemical, biochemical, environmental and social factors that influence children during critical periods of development. To date, research in the area of human developmental neurotoxicology focuses primarily on global measures of sensory-motor development and cognition. However, human studies elucidating the biological basis for developmental and behavioral disorders due to environmental toxicant exposure are lacking. Although gross brain structure appears normal, underlying problems must exist at a neural level. This project seeks to correlate childhood environmental lead exposure with changes in brain structure, neurochemistry and function assessed with magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Cortical and subcortical brain volumes will be determined with high resolution MRI. Neuronal and glial cell markers (N-acetyl aspartate, creatine, cholines and myo-inositol) will be measured using proton MRS. These structural and chemical measures will also be correlated with behavioral measures from the young adult participants of the Cincinnati Lead Study (CLS). These participants represent a unique and ideal study cohort of approximately 240 subjects with detailed histories of exposure and behavioral outcomes in lead exposed children monitored for approximately 20 years. As this cohort enters young adulthood, associations between childhood lead exposure and antisocial behaviors are emerging. While MRI and MRS provide structural and metabolic measures relevant to lead exposure, the significance to behavioral measures is limited. A pilot study (n=40) examining language, working memory and attention in combination with functional magnetic resonance imaging (fMRI) will also be performed to better investigate the correlation of functional and behavioral deficits.