This application is part of the competitive renewal for the "Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD)" in response to RFA-AA-12-004. Moving forward with the new theme for our project "brain connectivity in FASDs," we propose to build on our work investigating the impact of prenatal alcohol exposure (AE) on the long-term development of the brain. Specifically, we will leverage advances in the field to implement two new imaging modalities to complement our existing work to address how structural and functional brain connectivity is affected, both cross-sectionally and longitudinally and how connectivity relates to cognitive function and facial dysmorphology in children with AE. The ultimate goal of this renewal application remains the same, to determine if innovative techniques can be used to identify brain alterations, neurobehavioral deficits and facial characteristics and relationships between these variables to help further define/diagnose prenatal alcohol spectrum disorders (FASD). This timely project will apply a cutting-edge multimodal Magnetic Resonance Imaging (MRI) protocols and sophisticated image analyses to study 240 children (120 with AE) longitudinally studied across 4 data collection sites. While this brain imaging project can independently achieve some of the goals of the CIFASD by identifying brain structural and functional connectivity abnormalities across the broad spectrum of FASDs, critically this funding opportunity will allow the assessment of relationships between the brain, neurocognitive deficits and facial dysmorphology leveraging our active collaborations with the neurobehavioral project (Mattson PI), the facial imaging project (Foroud PI), and the dysmorphology core (Jones PI). Controlled animal studies are essential to determine timing and dosages of prenatal alcohol that result in FASDs, but human imaging studies are essential to corroborate anatomical findings across species that will be facilitated by projects in the basic sciences (Sulik PI). Thus, by capitalizing on existing CIFASD infrastructure, this project will provide critical new knowledge concerning the effects of AE on brain structure, function, behavior assessed cross-sectionally;in addition, longitudinal examinations will determine if AE effects are static, or changing during childhood and adolescence. New knowledge gained through investigations during the renewal period could have strong implications for potential future interventions, given that the brain changes dramatically in even typically developing kids, and we know from animal studies that environment and experience (enriched environment vs. deprived, etc.) shape the way the brain develops. If trajectories of developmental change throughout childhood are impacted by damage resulting from teratogenic exposure to alcohol in utero, it could be possible to ultimately shift trajectories for the better in these children throuh interventions targeted towards brain regions and cognitive functions most affected by AE.

Public Health Relevance

Understanding the neurobiological consequences of prenatal alcohol exposure is a fundamental first step for determining when and how to best intervene to improve cognitive and functional outcomes of affected individuals. While prenatal alcohol exposure is the leading preventable cause of intellectual disabilities, the prevalence of fetal alcohol syndrome is not declining, and the prevalence of those negatively affected by prenatal alcohol exposure, but without the defining facial dysmorphology to warrant the full FAS diagnosis is likely much higher. Thus, while prevention is key, developing intervention strategies is still a priority, and the brain imaging investigations proposed here can help drive these effort forward.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZAA1-CC (02))
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Dunty, Jr, William
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Children's Hospital of Los Angeles
Los Angeles
United States
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Yang, Yaling; Phillips, Owen R; Kan, Eric et al. (2012) Callosal thickness reductions relate to facial dysmorphology in fetal alcohol spectrum disorders. Alcohol Clin Exp Res 36:798-806
Roussotte, Florence F; Rudie, Jeffrey D; Smith, Lynne et al. (2012) Frontostriatal connectivity in children during working memory and the effects of prenatal methamphetamine, alcohol, and polydrug exposure. Dev Neurosci 34:43-57
Yang, Yaling; Roussotte, Florence; Kan, Eric et al. (2012) Abnormal cortical thickness alterations in fetal alcohol spectrum disorders and their relationships with facial dysmorphology. Cereb Cortex 22:1170-9
Colby, John B; Soderberg, Lindsay; Lebel, Catherine et al. (2012) Along-tract statistics allow for enhanced tractography analysis. Neuroimage 59:3227-42
Roussotte, Florence F; Bramen, Jennifer E; Nunez, S Christopher et al. (2011) Abnormal brain activation during working memory in children with prenatal exposure to drugs of abuse: the effects of methamphetamine, alcohol, and polydrug exposure. Neuroimage 54:3067-75
Nuñez, S Christopher; Dapretto, Mirella; Katzir, Tami et al. (2011) fMRI of syntactic processing in typically developing children: structural correlates in the inferior frontal gyrus. Dev Cogn Neurosci 1:313-23
Sowell, Elizabeth R; Leow, Alex D; Bookheimer, Susan Y et al. (2010) Differentiating prenatal exposure to methamphetamine and alcohol versus alcohol and not methamphetamine using tensor-based brain morphometry and discriminant analysis. J Neurosci 30:3876-85
Roussotte, Florence; Soderberg, Lindsay; Sowell, Elizabeth (2010) Structural, metabolic, and functional brain abnormalities as a result of prenatal exposure to drugs of abuse: evidence from neuroimaging. Neuropsychol Rev 20:376-97
Mattson, Sarah N; Foroud, Tatiana; Sowell, Elizabeth R et al. (2010) Collaborative initiative on fetal alcohol spectrum disorders: methodology of clinical projects. Alcohol 44:635-41
Sowell, Elizabeth R; Johnson, Arianne; Kan, Eric et al. (2008) Mapping white matter integrity and neurobehavioral correlates in children with fetal alcohol spectrum disorders. J Neurosci 28:1313-9