Prenatal cocaine (PNCE) and alcohol exposure (PNAE) result in sustained behavioral deficits similar in many respects to attention deficit hyperactivity disorder (ADHD). While this similarity suggests the involvement of similar or overlapping neural circuits in all three groups, subtle differences in the specific deficits and their differential responsiveness to stimulants suggest differences in the nature of the disruptions within a specific circuit and/or disruptions in non-overlapping circuits. Studies in animals suggest that PNCE results in a post-synaptic defect in dopamine (DA) neurotransmission that is refractory to stimulants, such as amphetamine (AMPH) or methylphenidate (MPH). In human studies, the data are less clear, reflecting, at least in part, the difficulty of identifying subjects with pure PNCE or PNAE, and, in part, the fact that tools for measuring circuit function have only recently become available. This project will bring together three groups of researchers with expertise in developmental consequences of alcohol and cocaine exposure in utero, functional and structural neuroimaging, and ADHD, with the overarching goal of characterizing the neural correlates of ADHD behaviors in PNCE and PNAE individuals, using a combination of detailed neurocognitive testing, ERP, and functional, structural, and diffusion tensor (DTI) MRI. We will study a well characterized cohort of 18-year-old, African American adolescents, whose PNCE and PNAE were ascertained prospectively during gestation. This cohort is unique in that recruitment was stratified to minimize the confounding of alcohol and cocaine. The study has the following Specific Aims: 1) To use fMRI to confirm that individuals with PNCE, PNAE, and idiopathic ADHD have a functional impairment in fronto-striatal circuits and that additional circuit dysfunctions contribute to behavioral deficits in PNAE; 2) To test the hypothesis that the circuit defect in PNCE-associated ADHD is postsynaptic and, therefore, unresponsive to MPH; 3) To use structural MRI and DTI to examine the contribution of structural abnormalities to the functional impairment in neural circuitry linked to ADHD-related deficits; 4) To identify the neural correlates of dyscalculia in individuals with PNAE and test the hypothesis that PNAE is characterized by a specific deficit in activation of parietal networks subserving number processing.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZDA1-MXS-M (22))
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Borek, Nicolette T
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Vanderbilt University Medical Center
Schools of Medicine
United States
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