Behavioral Characteristics and Neural Correlates of Reading Impairment in FASD

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DESCRIPTION (provided by applicant): Although a few studies have documented poorer reading performance in children with fetal alcohol spectrum disorders (FASD), relatively little is known about the specific aspects of reading that may be affected. In two recent studies, PI Jacobson and her colleagues at University of Cape Town (UCT) found specific effects of prenatal alcohol exposure on reading comprehension, which were mediated by deficits in reading fluency and phonological awareness. Although the neural mechanisms that underlie reading impairment have been studied extensively in children with developmental dyslexia (DD), the neural correlates of reading impairment in FASD have not previously been investigated. Studies of DD by PI Gaab at Boston Children's Hospital (BCH) and others have revealed morphological and functional alterations in inferior frontal, posterior perisylvian, and two left hemispheric posterior brain regions and poorer structural integrity in the left arcuate fasciculus (AF). Two well-characterized longitudinal cohorts of children with heavy prenatal alcohol exposure and healthy controls in Cape Town, South Africa, will be studied-one comprised of 150 adolescents; the other, of 131 preschool-age children. The aims are (1) To systematically characterize the specific aspects of reading and pre-reading skills that are affected in FASD; (2) To examine the degree to which the relation between prenatal alcohol exposure and reading may be attributable to alcohol-related deficits in language skills, executive function, working memory, and/or IQ; (3) To test the hypothesis that, as in DD, reading impairment in alcohol-exposed adolescents is associated with structural and functional deficits in inferior frontal, posterior perisylvian, and left hemispheric posterior brain regions and their underlying white matter tracts, including the AF; (4) To test the hypothesis that, as in DD, fetal alcohol-related neural deficits during phonological processing (measured using fMRI) and structural alterations in reading-related brain regions predate reading onset and are already evident in preschool children; (5) To test the hypothesis that poorer white matter integrity in the left AF in the newborn brain will predict fetal alcohol-related pre-reading deficits at preschool age. Since 1998, PI Jacobson and her colleagues at UCT have been studying FASD in the Cape Coloured (mixed ancestry) community, in which incidence of FAS is among the highest in the world. Although they and others have conducted neuroimaging studies of working memory, response inhibition, eyeblink conditioning, and number processing, this will be the first study to examine the neural correlates of reading impairment in FASD. Since 2004, PI Gaab has been studying alterations of the neural network that mediates reading impairment in DD. This will be the first study to examine how a neurotoxic insult from an environmental exposure may affect the structural and functional brain networks that mediate reading. The proposed study will significantly enhance the research capability and direction of both the UCT and BCH laboratories and potentially contribute to development of innovative targeted interventions for this major public health problem in the US, South Africa, and worldwide.