Research on fetal alcohol spectrum disorder (FASD) and attention deficit hyperactivity disorder (ADHD) has been hampered by a lack of specificity in behavioral diagnostic criteria and limited understanding of the neural substrates that mediate the observed cognitive deficits. Phenotypically similar deficits seen in these disorders are difficult to distinguish despite different etiologies. Neurobehavioral data from PI Jacobson's laboratory suggest that fetal alcohol-related impairment in arithmetic is mediated by a deficit in the core quantity system involving the ability to mentally represent and manipulate number (numerosity), whereas in ADHD, poor arithmetic appears to be mediated by impaired executive function. PI Berger has developed innovative paradigms using event-related potentials (ERP) to examine the neural bases of arithmetic and attention, which make it possible to identify discrete components underlying number processing, including magnitude representation, error detection, selective attention, and response inhibition. We propose to conduct the first ERP study to compare number processing in children with and without FASD and/or ADHD to advance understanding of the neural substrates that are compromised in each of these disorders, thereby potentially improving differential diagnosis. 100 young adolescents (12.5- 15 years of age) from a well-characterized, prospective longitudinal cohort will be selected from four groups: FASD only;ADHD only;FASD + ADHD;non-exposed, unaffected controls.
The aims of the study are (1) to characterize the deficits in neurocognitive processes that underlie number processing in FASD and ADHD, using a standardized mathematics achievement test and a culture-free battery based on contemporary theories of mathematical cognition;(2) to administer three ERP paradigms to examine which numerical and control processes of number processing are affected in each of these disorders-non-symbolic representation of quantity (numerosity), executive monitoring of arithmetic errors, selective attention, response inhibition/cognitive control;(3) to examine the degree to which latency and amplitude of the principal ERP waveforms that appear to be altered in FASD or ADHD are related to performance on the behavioral mathematics assessments. Exploratory analyses will also be conducted to determine the degree to which effects seen on the ERP components are specific to each of these disorders or attributable to deficits in overall intellectual and/or executive function and the degree to which total brain, gray or white matter volume, or volumes of the anterior cingulate cortex or the superior and inferior parietal region may mediate the observed effects. The proposed study will be conducted in Cape Town, South Africa, a highly cost-effective venue for this study, given the unusually large number of children with FAS available at a single site and the availability of a 128- channel Electrical Geodesics, Inc., system to acquire the ERP data.

Public Health Relevance

Fetal alcohol spectrum disorders (FASD) and attention deficit hyperactivity disorder (ADHD) are major public health problems in the U.S. and worldwide. Phenotypically similar problems in attention and hyperactivity seen in these two disorders are difficult to distinguish despite different etiologies. Moreover, some children with ADHD may have been exposed to alcohol during pregnancy, potentially leading to a different pattern of behavioral symptoms and underlying impairment than that seen in idiopathic ADHD. Given that number processing and executive function are impaired in both disorders, it is often difficult to make a differential diagnosis. The proposed study will use innovative event-related potential (ERP) paradigms to better characterize the neural bases of the number processing and error monitoring deficits seen in these disorders. The data to be generated from these innovative paradigms will lead to improved understanding of the pathophysiology of both FASD and ADHD, which can, in turn, improve differential diagnosis and contribute to the development of novel behavioral and pharmaceutical treatments better targeted to the specific deficits that characterize each of these disorders.

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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