Mechanisms of Attention Deficits in Children with Heavy Prenatal Alcohol Exposure

描述(由申请人提供)：胎儿酒精谱系障碍(FASD)的特点是发生在整个谱系的严重神经行为障碍。这些缺陷的概况正在形成，但这种概况的临床应用需要继续研究，以提高其准确性和特异性。FASD经常注意到的一个缺陷是在注意力领域。在前人关于注意、记录空间定向缺陷和持续视觉注意的研究的基础上，我们建议使用最新的方法论对视觉注意缺陷的机制进行更广泛的研究。更具体地说，这项拟议的研究将使用注意力网络测试(ANT)，该测试旨在评估三种注意力网络(定向、警报、执行控制)，它们是视觉注意力的基础，依赖于可分离的大脑区域和神经递质系统的完整性。神经心理学和功能磁共振成像(FMRI)版本的ANT将被用来评估患有FASD和典型发育中的对照组的儿童与三个注意网络相关的不同行为和大脑反应。FASD组内网络中不同损害的发现可能有助于确定这一人群中相对强弱和缺陷的领域，有助于形成产前重度酒精暴露的神经行为特征。此外，分析血氧水平依赖(BOLD)对蚂蚁的反应将允许检查观察到的注意力缺陷的神经基础。基于以前的研究，我们假设FASD组的警报和执行控制网络的特征是相对更大的缺陷。目前应用的另一个目标是通过将全量表智商(FSIQ)得分低于平均范围(FSIQ&lt；85)的儿童纳入我们的对照组来检查观察到的效果的特异性。这将使我们能够比较控制总体智商和不控制整体智商的小组之间的注意力表现。我们假设，即使在没有智商差异的情况下，观察到的注意力缺陷也会发生。我们计划用ANT的神经心理学版本对两组(FASD和对照组)的80名儿童(8-12岁)和60名青少年(13-16岁)进行fMRI测试。对于这两项任务，控制组将比FASD组更大，以允许智商低于平均水平的额外受试者。这项拟议的研究与NIAAA 2009-2014年的战略计划一致，该计划将完善FASD的神经发育特征列为关键研究需要。我们对FASD的神经心理学特征的关注，包括神经心理学和功能磁共振成像程序，以及我们对注意力和智商降低之间的关系的兴趣，直接解决了这些建议。 公共卫生相关性：该项目与围绕大量产前酒精暴露的行为影响的公共卫生问题直接相关。由此产生的数据将澄清胎儿酒精谱系障碍中注意力缺陷的性质和神经基础，因此将有助于完善这一人群特有的影响概况，并改善对受酒精影响的个人的诊断。改善对这些特征的描述和识别将通过识别注意力的各个方面以及受严重产前酒精暴露影响的潜在大脑区域和神经递质系统，最终导致改善治疗。

DESCRIPTION (provided by applicant): The hallmark of fetal alcohol spectrum disorders (FASD) is the significant neurobehavioral impairment that occurs across the spectrum. A profile of these deficits is emerging, but the clinical utility of such a profile requires continued research to improve its accuracy and specificity. One deficit that is often noted in FASD is in the domain of attention. Based on previous studies of attention, documenting deficits in spatial orienting and sustained visual attention, we propose a broadened investigation of the mechanisms of visual attention deficits using state of the art methodology. More specifically, the proposed study will use the Attention Network Test (ANT), which was designed to assess three attention networks (orient, alert, executive control) that underlie visual attention and are dependent on the integrity of dissociable brain regions and neurotransmitter systems. Both neuropsychological and functional magnetic resonance imaging (fMRI) versions of the ANT will be used to assess differential behavioral and brain response related to the three attention networks in children with FASD and typically developing controls. Findings of differential impairments across the networks within the FASD group may help to identify areas of relative strengths and deficits in this population, contributing to the developing neurobehavioral profile of heavy prenatal alcohol exposure. In addition, analyzing blood oxygen level dependent (BOLD) response to the ANT will allow for examination of the neural underpinnings of observed attention deficits. Based on previous studies, we hypothesize a profile characterized by relatively greater deficits in the alerting and executive control networks in the FASD group. An additional goal of the current application is to examine the specificity of observed effects by including children with full scale IQ (FSIQ) scores below the average range (FSIQ<85) in our control group. This will allow us to compare the attention performance between the groups with and without controlling overall IQ. We hypothesize that the observed attention deficits will occur even in the absence of IQ differences. We plan to test 80 children (ages 8-12y) in two groups (FASD and Control) with the neuropsychological version of the ANT and 60 adolescents (ages 13-16y) on the fMRI version. For both tasks, the control group will be larger than the FASD group to allow for the additional subjects with below average IQ scores. The proposed study is consistent with the NIAAA strategic plan for 2009-2014, which cited refining the neurodevelopmental signature of FASD as a critical research need. Our focus on neuropsychological features of FASD, the inclusion of neuropsychological and fMRI procedures, and our interest in the relation between attention and lowered IQ directly addresses these recommendations. PUBLIC HEALTH RELEVANCE: This project is directly relevant to public health concerns surrounding the behavioral effects of heavy prenatal alcohol exposure. The resulting data will clarify the nature and neural underpinnings of attention deficits in fetal alcohol spectrum disorders, and as a result will help refine the profile of effects that are specific to this population and improve diagnosis of alcohol-affected individuals. Improved delineation and identification of these features will ultimately lead to improved treatment by indentifying aspects of attention as well as underlying brain regions and neurotransmitter systems affected by heavy prenatal alcohol exposure.