Behavioral Characteristics and Neural Correlates of Reading Impairment in FASD

描述（由申请人提供）：尽管有一些研究证明患有胎儿酒精谱系障碍（FASD）的儿童的阅读能力较差，但对阅读可能受到影响的具体方面所知相对较少。在最近的两项研究中，开普敦大学（UCT）的PI Jacobson和她的同事发现，产前酒精暴露对阅读理解的特定影响是由阅读流畅性和语音意识缺陷介导的。尽管在发展性阅读障碍（DD）儿童中阅读障碍的神经机制已经被广泛研究，但FASD中阅读障碍的神经相关因素尚未被研究过。波士顿儿童医院（BCH）的PI Gaab和其他人对DD的研究显示，额下、后周和两个左半球后脑区域的形态学和功能改变，以及左弓状束（AF）的结构完整性较差。将对南非开普敦产前重度酒精暴露儿童和健康对照者进行两组特征明确的纵向队列研究——一组由150名青少年组成；另一组是131名学龄前儿童。目的是：(1)系统地描述在FASD中受到影响的阅读和阅读前技能的具体方面；(2)研究产前酒精暴露与阅读之间的关系在多大程度上可归因于酒精相关的语言技能、执行功能、工作记忆和/或智商缺陷；(3)验证如下假设：与DD一样，酒精暴露青少年的阅读障碍与额下、后后、左半球后脑区域及其潜在的白质束（包括心房）的结构和功能缺陷有关；(4)为了验证以下假设：与DD一样，胎儿在语音处理过程中与酒精相关的神经缺陷（使用功能磁共振成像测量）和阅读相关大脑区域的结构改变早于阅读开始，并且在学龄前儿童中已经很明显；(5)验证新生儿左心房房颤白质完整性较差与胎儿学龄前酒精相关的阅读前缺陷相关的假设。自1998年以来，PI Jacobson和她在UCT的同事们一直在研究Cape colored（混合血统）社区的FASD，该社区的FAS发病率是世界上最高的。虽然他们和其他人已经对工作记忆、反应抑制、眨眼条件反射和数字处理进行了神经成像研究，但这将是第一次研究FASD中阅读障碍的神经相关性。自2004年以来，PI Gaab一直在研究DD中介导阅读障碍的神经网络的改变。这将是第一个研究环境暴露的神经毒性损害如何影响介导阅读的大脑结构和功能网络的研究。拟议的研究将大大提高UCT和BCH实验室的研究能力和方向，并可能有助于开发针对美国、南非和全世界这一重大公共卫生问题的创新针对性干预措施。

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.