Prenatal alcohol exposure is known to result in a variety of deleterious effects from the fetal alcohol syndrome (FAS) to less obvious birth defects and cognitive and behavioral anomalies. Fetal Alcohol Spectrum Disorder(s) (FASD) is the nondiagnostic term used to reflect the range of outcomes from such exposure. FASD represents a major public health issue having a considerable social and economic toll, with prevalence estimates as high as 2-5% of young school children. Among the most devastating effects of prenatal alcohol exposure are those on the brain and their cognitive and behavioral sequelae. Prenatal alcohol exposure is associated with a wide array of cognitive and behavioral issues, including deficits in learning, memory, attention, executive functioning, and general intellectual functioning. Neuroimaging studies support these findings and provide links between prenatal alcohol exposure, brain alterations, and cognitive and behavioral changes. One domain that may be particularly sensitive to prenatal alcohol exposure is spatial working memory (SWM), although the nature and specificity of these deficits have not been thoroughly examined. Furthermore, only two neuroimaging studies have specifically examined SWM in FASD and the findings have been inconclusive, and some methodological concerns raised. The current proposal aims to clarify and extend previous work by using multimodal imaging techniques to assess SWM in adolescents with histories of heavy prenatal alcohol exposure. Two groups of adolescents will be assessed: non-exposed, typically-developing adolescents and adolescents with FASD.
The specific aims of this proposal are threefold: 1) to compare blood oxygen level-dependent (BOLD) response during a SWM task between groups using functional magnetic resonance imaging (fMRI)~ 2) to examine the neural network underlying the areas of activation post hoc by analyzing functional connectivity between task-relevant regions~ and 3) to examine white matter microstructure underlying the functionally-connected brain regions (assessed in aim 2) using diffusion tensor imaging (DTI) and its relation to the BOLD activation patterns (assessed in aim 1). These analyses will extend our understanding of how prenatal alcohol exposure alters brain structure and function, and thus, cognitive ability. By highlighting the effects of heavy prenatal alcohol exposure on brain function and underlying structure and how these relate to specific neurocognitive effects, we can improve the diagnosis of alcohol-affected individuals and develop more effective treatment and intervention programs.

Public Health Relevance

Working memory deficits have been reported in children with fetal alcohol spectrum disorders (FASD), and more specifically research suggests that within the working memory domain, spatial working memory (SWM) is particularly sensitive to the effects of prenatal alcohol exposure. Understanding the brain mechanisms underlying SWM in FASD will contribute to the development of more effective interventions that target specific deficits. I addition, the combined use of functional and structural imaging techniques will help identify objective biomarkers of FASD, which will enhance diagnostic accuracy and identification.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Predoctoral Individual National Research Service Award (F31)
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Health Services Research Review Subcommittee (AA)
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Matochik, John A
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San Diego State University
Schools of Arts and Sciences
San Diego
United States
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Moore, Eileen M; Infante, M Alejandra; Migliorini, Robyn et al. (2016) Pituitary lacks sexual dimorphism and displays reduced signal intensity on T1-weighted MRI in adolescents with histories of heavy prenatal alcohol exposure. Neurotoxicol Teratol 57:106-111
Infante, M Alejandra; Moore, Eileen M; Nguyen, Tanya T et al. (2015) Objective assessment of ADHD core symptoms in children with heavy prenatal alcohol exposure. Physiol Behav 148:45-50
Infante, M Alejandra; Moore, Eileen M; Bischoff-Grethe, Amanda et al. (2015) Atypical cortical gyrification in adolescents with histories of heavy prenatal alcohol exposure. Brain Res 1624:446-54
Migliorini, Robyn; Moore, Eileen M; Glass, Leila et al. (2015) Anterior cingulate cortex surface area relates to behavioral inhibition in adolescents with and without heavy prenatal alcohol exposure. Behav Brain Res 292:26-35
Moore, Eileen M; Migliorini, Robyn; Infante, M Alejandra et al. (2014) Fetal Alcohol Spectrum Disorders: Recent Neuroimaging Findings. Curr Dev Disord Rep 1:161-172