Owing to a legacy of industrial pollution throughout the 20th Century, families and children in the in the United States are exposed to mixtures of environmental contaminants;one of the most significant contaminants is polychlorinated biphenyls (PCBS). PCBs demonstrate multiple forms of neurotoxicity, most notably with regard to dopamine (Mariussen &Fonnum, 2006) and white matter development (Sharlin et al. 2006;Preliminary Studies). This investigative team has shown a link between exposure to PCBs and impulsive behavior, or more specifically, impaired response inhibition (Stewart et al. 2003, 2005, 2006). This highly circumscribed behavioral deficit, characterized by an impaired ability to withhold responses, is associated with a rich brain imaging literature that implicates a number of frontal and fronto-striatal structures in its regulation. The importance of the link between response inhibition and brain function in this cohort is underscored by the finding of significant reductions in white matter throughout the cerebral cortex, especially the frontal cortex, in our PCB-exposed children. We intend to investigate whether PCB exposure and impaired response inhibition is related to impaired activation of the prefrontal cortex (inferior) and if those activational changes are related to reductions in white matter integrity in frontostriatal tracts. The proposed study will capitalize on an 18 year longitudinal study of child development, in combination with state-of-the-art neuroimaging approaches at the Rochester Center for Brain Imaging (RCBI).
The Specific Aims are:
AIM #1) To test the hypothesis that altered activation of the prefrontal cortex (PFC) underlies the PCB-related deficits in impulse control (response inhibition).
AIM #2) To test the hypothesis that frontostriatal connectivity is reduced in PCB exposed children.

Public Health Relevance

There is reasonable evidence from research studies that indicate that prenatal exposure to PCBs produces impairments in cognitive and behavioral development in children. The Oswego Project represents one of the few major, longitudinal studies in the United States designed to assess the effects of exposure to low levels of PCBs on child development. The stable nature of the cohort, the 16 years of experience the principal investigators have with these cohorts, the well-established testing protocols, and the extensive database of exposure, outcome and potentially confounding/mediating variables permit rigorous assessment of the impact of prenatal PCB exposure in the teen years.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project (R01)
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Neurological, Aging and Musculoskeletal Epidemiology (NAME)
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Kirshner, Annette G
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College at Oswego
Schools of Arts and Sciences
United States
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Stewart, Paul W; Reihman, Jacqueline; Lonky, Edward et al. (2012) Issues in the interpretation of associations of PCBs and IQ. Neurotoxicol Teratol 34:96-107
Gump, Brooks B; Mackenzie, James A; Bendinskas, Kestutis et al. (2011) Low-level Pb and cardiovascular responses to acute stress in children: the role of cardiac autonomic regulation. Neurotoxicol Teratol 33:212-9
Gump, Brooks B; Reihman, Jacki; Stewart, Paul et al. (2009) Trajectories of maternal depressive symptoms over her child's life span: relation to adrenocortical, cardiovascular, and emotional functioning in children. Dev Psychopathol 21:207-25
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Stewart, Paul W; Lonky, Edward; Reihman, Jacqueline et al. (2008) The relationship between prenatal PCB exposure and intelligence (IQ) in 9-year-old children. Environ Health Perspect 116:1416-22
Gump, Brooks B; Stewart, Paul; Reihman, Jacki et al. (2008) Low-level prenatal and postnatal blood lead exposure and adrenocortical responses to acute stress in children. Environ Health Perspect 116:249-55
Gump, Brooks B; Reihman, Jacki; Stewart, Paul et al. (2007) Blood lead (Pb) levels: a potential environmental mechanism explaining the relation between socioeconomic status and cardiovascular reactivity in children. Health Psychol 26:296-304
Stewart, Paul W; Sargent, David M; Reihman, Jacqueline et al. (2006) Response inhibition during Differential Reinforcement of Low Rates (DRL) schedules may be sensitive to low-level polychlorinated biphenyl, methylmercury, and lead exposure in children. Environ Health Perspect 114:1923-9
Stewart, Paul; Reihman, Jacqueline; Gump, Brooks et al. (2005) Response inhibition at 8 and 9 1/2 years of age in children prenatally exposed to PCBs. Neurotoxicol Teratol 27:771-80
Gump, Brooks B; Stewart, Paul; Reihman, Jacki et al. (2005) Prenatal and early childhood blood lead levels and cardiovascular functioning in 9(1/2) year old children. Neurotoxicol Teratol 27:655-65

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