Neuromaturation in Adults with FASD

About This Grant

PROJECT SUMMARY/ABSTRACT It has been fifty years since the identification of fetal alcohol spectrum disorders (FASD), and yet there remain virtually no studies of brain morphology and function in middle aged and older adults with FASD. Profound and detrimental impacts of prenatal alcohol exposure (PAE) on brain development have been consistently observed in children and adolescents. These impacts include smaller total brain volume and smaller volumes of frontal and medial temporal areas; less fractional anisotropy; attenuated default mode resting state network deactivation and altered structural and functional connectivity; abnormalities in shape and size of the corpus callosum; and smaller cerebellum and basal ganglia. Cross-sectional analysis of the relation between age and volume of these structures suggests that adolescents and young adults with FASD have atypical brain maturation patterns indicative of both disrupted developmental processes and accelerated aging. While this suggestion is supported by several multi-site longitudinal analyses conducted by the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD) as well as a variety of other smaller cross-sectional and longitudinal studies in younger cohorts, to date there remain no longitudinal studies examining brain maturation in middle-aged and older adults with FASD. While emerging research suggests that, at midlife, the brain impacts of PAE observed in younger ages do indeed extend into middle-age and beyond, longitudinal studies in this area are essential to understand the trajectory of brain maturation as individuals with FASD age. To address this critical evidence gap, this project will conduct ground-breaking longitudinal and cross-sectional research focusing on age-related brain changes in 60 adults with FASD and 30 healthy comparison (HC) adults aged 30-65y at baseline. All participants will complete an evidence-based cognitive test battery to assess function in multiple cognitive domains. Longitudinal evaluation will use anatomical, diffusion, and resting state functional neuroimaging techniques, and cross- sectional methods will examine white matter hyperintensities, cerebral blood flow, and task inhibition. Imaging studies will employ state-of-the-art techniques specifically developed to evaluate the brain longitudinally. Our group has already completed 90 baseline scans (59 with FASD, 31 HC) using these parameters at the University of Washington as part of a previous R01 project (R01 AA026994). We will collect 21 additional baseline scans during Y1 (12 with FASD, 9 HC) and follow up scans in Y1-Y5 for a final sample of 90 individuals with two neuroimaging sessions averaging five years apart. This project stands to 1) provide critical information about the impact of PAE on the brain in middle and older adulthood, 2) establish a biological basis for neurobehavioral deficits, and 3) identify novel biological targets for treatment of adults with FASD.