Prenatal alcohol exposure (PAE) alters the structure and function of specific brain regions, and these alterations correspond with cognitive, behavioral and neurophysiological deficits; however very little is known about how structural and functional connectivity among regions may be altered. Enhanced understanding of how developmental trajectories are altered in individuals with a Fetal Alcohol Spectrum Disorder (FASD) is essential for the timing and design of specialized interventions, and for identifying sensitive periods during which maximal benefits may be achieved. Ultimately, early interventions can help improve healthy development of brain networks, and produce a more beneficial developmental trajectory. Structural (diffusion tensor imaging) and functional (resting state functional MRI) brain connectivity will be assessed using multimodal neuroimaging techniques in FASD youth and age-matched control participants. Moreover, despite accumulating evidence from animal models, nothing is yet known about how these trajectories of brain development and connectivity differ between FASD boys and girls. It also remains to be investigated if the effects of PAE on altering hormone systems is involved with brain abnormalities in FASD boys and girls. Thus, the present proposal aims to use a multimodal imaging approach to assess sex differences in the effects of PAE on brain connectivity. The proposed research project will assess hormone function in PAE boys and girls, and hormones will be integrated with measures of structural and functional brain connectivity. Integrated brain and hormone measures will be correlated with measures of cognitive performance (WISC-IV). The proposed findings have implications for cognitive, behavioral and mental health problems that occur at a high prevalence among individuals with an FASD. Results will help identify sexually dimorphic effects of PAE on underlying neural networks in order to inform future intervention and treatment strategies targeted to a specific sex and specific impairments in neural networks. Enhanced interventions applied during key developmental time periods may help relieve the burden on health care systems by preventing/reducing a range of health problems later in life.

Public Health Relevance

Understanding the effects of prenatal alcohol exposure on brain development is essential for creating effective intervention strategies that are specialized for this vulnerable population. Specifically, the present proposal aims to elucidate sexually dimorphic effects of prenatal alcohol exposure on structural and functional connectivity among brain regions throughout development, as well as the influence of gonadal and stress hormones. Results from the proposed studies will help identify sensitive developmental periods when environmental and physiological interventions may prove most effective for producing long lasting benefits to individuals with a FASD.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Postdoctoral Individual National Research Service Award (F32)
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Neuroscience Review Subcommittee (AA)
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Matochik, John A
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Children's Hospital of Los Angeles
Los Angeles
United States
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Herting, Megan M; Kim, Robert; Uban, Kristina A et al. (2017) Longitudinal changes in pubertal maturation and white matter microstructure. Psychoneuroendocrinology 81:70-79
Uban, K A; Herting, M M; Wozniak, J R et al. (2017) Sex differences in associations between white matter microstructure and gonadal hormones in children and adolescents with prenatal alcohol exposure. Psychoneuroendocrinology 83:111-121