Research on and treatment of fetal alcohol spectrum disorder (FASD) have been hampered by a lack of specificity in behavioral diagnostic criteria and limited understanding of the neural substrates that mediate the observed cognitive deficits. Previous studies have identified arithmetic as a particularly sensitive developmental endpoint in FASD. Data from our Detroit cohort suggest that fetal alcohol-related impairment in arithmetic is mediated by a specific deficit in the core quantity system involving the ability to mentally represent and manipulate number, which has been linked to alcohol-related deficits in parietal lobe function in neuroimaging studies. This deficit appears to be evident already in infancy, as indicated by pilot data from our Cape Town cohort suggesting poorer performance by alcohol-exposed infants on the Wynn numerosity paradigm. It is not clear, however, whether impaired performance on this paradigm reflects a specific deficit in representation of quantity;a deficit in error detection, an aspect of execution function that has also been reported in alcohol- exposed children;or more general perceptual or cognitive impairment in the exposed infants. The event-related potentials (ERP) technique provides a unique opportunity to collect precise information regarding the time course and specific components of information processing that can advance understanding of the specific deficits in number processing and error detection in alcohol-exposed infants seen in the Wynn paradigm. 50 infants, whose mothers will have been recruited in mid-pregnancy, will be studied at 6 months postpartum- 25 heavy exposed and 25 non-exposed controls, matched for maternal education and gestational age when antenatal care was initiated.
The aims are (1) to confirm that the adverse effect of fetal alcohol exposure on number processing can be detected behaviorally in infancy using the Wynn numerosity paradigm;(2) to use ERP to specify which stages and components of numerosity processing are affected by fetal alcohol exposure in this paradigm-magnitude representation, error monitoring, or both;(3) to use a novel ERP task to determine whether the alcohol-related numerosity deficit seen in the Wynn paradigm is specific to the abstract representation of small quantities rather than perceptual features of the stimulus display that tend to covary with numerosity (e.g., density, total surface area). The proposed study will be conducted in Cape Town, South Africa, where there is an unusually high incidence of alcohol abuse and dependence in women of child-bearing age and the incidence of fetal alcohol syndrome is among the highest in the world. Cape Town is a highly cost-effective venue in which to conduct this study given the unusually large pool of heavily exposed infants available at a single site, the ongoing recruitment of an infant sample for a currently-funded R01 grant who can participate in this study, and the availability of a 128-channel Electrical Geodesics, Inc., system to acquire the ERP data.

Public Health Relevance

Fetal alcohol syndrome (FAS) and other alcohol-related disorders are an important health problem worldwide and a major public health issue in South Africa. The long-term effects of these disorders include significant neurocognitive and behavioral impairment. This proposed ERP study will provide an opportunity to examine brain function in relation to two promising neurocognitive biomarkers of fetal alcohol spectrum disorder (FASD)- numeric magnitude comparison and error detection-very early in development. The identification of biomarkers can improve FASD diagnosis by grounding it in specific aspects of central nervous system function that can be linked biologically to fetal alcohol exposure. Given this link to specific neural pathways, these data can also provide important information about the pathophysiology of FASD, which can, in turn, contribute to the development of treatments that are better targeted to the specific deficits that characterize this disorder.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Exploratory/Developmental Grants (R21)
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Health Services Research Review Subcommittee (AA)
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Matochik, John A
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Wayne State University
Schools of Medicine
United States
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