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）的标志是发生在整个谱系中的显著神经行为损伤。这些缺陷的轮廓正在出现，但这种轮廓的临床实用性需要继续研究，以提高其准确性和特异性。在FASD中经常注意到的一个缺陷是注意力。基于以往的研究注意，记录赤字的空间定向和持续的视觉注意，我们提出了一个扩大调查的视觉注意缺陷的机制，使用最先进的方法。更具体地说，拟议的研究将使用注意力网络测试（ANT），该测试旨在评估三个注意力网络（定向，警觉，执行控制），这些网络是视觉注意力的基础，并依赖于可分离的大脑区域和神经递质系统的完整性。ANT的神经心理学和功能性磁共振成像（fMRI）版本将用于评估与FASD儿童和典型发育对照组的三个注意力网络相关的差异行为和大脑反应。FASD组内网络差异性损伤的发现可能有助于确定该人群的相对优势和缺陷领域，有助于发展产前酒精暴露的神经行为特征。此外，分析对ANT的血氧水平依赖性（BOLD）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，我们假设一个配置文件的特点是相对较大的赤字在FASD组的警觉和执行控制网络。本申请的另一个目标是通过在我们的对照组中包括具有低于平均范围（FSIQ<85）的全量表IQ（FSIQ）分数的儿童来检查观察到的效果的特异性。这将使我们能够比较有和没有控制整体智商的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。我们计划测试80名儿童（8- 12岁），分为两组（FASD和对照组）与ANT的神经心理学版本和60名青少年（13- 16岁）的功能磁共振成像版本。对于这两项任务，对照组将大于FASD组，以允许IQ评分低于平均水平的额外受试者。该研究符合NIAAA 2009-2014年战略计划，该计划将FASD的神经发育特征作为关键研究需求。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关系的兴趣，直接解决了这些建议。 公共卫生相关性：该项目直接关系到围绕产前大量饮酒行为影响的公共卫生问题。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，因此将有助于完善该人群特有的影响特征，并改善对酒精影响个体的诊断。改善描绘和识别这些功能将最终导致改善治疗识别方面的注意力以及潜在的大脑区域和神经递质系统的影响，产前酒精暴露。

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.