An ERP Study of Infant Numerosity in Fetal Alcohol Syndrome

描述(申请人提供)：胎儿酒精谱系障碍(FASD)的研究和治疗一直受到行为诊断标准缺乏特异性和对调节所观察到的认知缺陷的神经底物的有限了解的阻碍。以前的研究发现，算术是FASD的一个特别敏感的发育终点。来自我们底特律队列的数据表明，胎儿酒精相关的算术障碍是由核心数量系统中涉及心理表征和操纵数字的能力的特定缺陷所调节的，这与神经成像研究中与酒精相关的顶叶功能缺陷有关。这一缺陷似乎在婴儿期就已经很明显了，正如我们开普敦队列的试点数据所表明的那样，酒精暴露的婴儿在永利数字范式上表现较差。然而，尚不清楚这一范式的表现受损是否反映了数量表征的具体缺陷；错误检测的缺陷，这也是酒精暴露儿童报告的执行功能的一个方面；还是暴露在酒精暴露的婴儿中更普遍的知觉或认知障碍。事件相关电位(ERP)技术提供了一个独特的机会来收集关于信息处理的时间进程和特定组成部分的准确信息，这可以促进对Wynn范式中看到的酒精暴露婴儿在数字处理和错误检测方面的特定缺陷的理解。50名婴儿的母亲将在孕中期招募，他们将在产后6个月进行研究-25名重度接触者和25名非接触者对照，在产前护理开始时，母亲的教育和胎龄相匹配。其目的是(1)证实胎儿酒精暴露对数字加工的不利影响可以使用永利数字范式在婴儿期以行为方式检测到；(2)使用事件相关电位来具体说明在该范式中胎儿酒精暴露对数字加工的哪些阶段和组成部分有影响--幅度表征、错误监控，或者两者兼而有之；(3)使用一项新颖的ERP任务来确定永利范式中看到的与酒精相关的数字缺陷是否是针对小数量的抽象表征，而不是倾向于与数字相关的刺激显示的知觉特征(例如，密度、总表面积)。这项拟议的研究将在南非开普敦进行，那里的育龄妇女酗酒和依赖酒精的发生率异常高，胎儿酒精综合症的发病率也是世界上最高的之一。开普敦是进行这项研究的极具成本效益的地点，因为在一个地点可以获得异常大的重度暴露婴儿池，正在为可以参与这项研究的当前资助的R01补助金招募婴儿样本，以及可获得128通道电气大地测量公司的系统来获取ERP数据。 公共卫生相关性：胎儿酒精综合征(FAS)和其他与酒精有关的疾病是世界范围内的一个重要健康问题，也是南非的一个主要公共卫生问题。这些疾病的长期影响包括严重的神经认知和行为障碍。这项拟议的ERP研究将提供一个机会，以检查与胎儿酒精谱系障碍(FASD)的两个有前景的神经认知生物标志物(数值幅度比较和错误检测)相关的大脑功能。生物标志物的识别可以改善FASD的诊断，方法是将其建立在中枢神经系统功能的特定方面，这些方面可以从生物学上与胎儿酒精暴露联系起来。鉴于这种与特定神经通路的联系，这些数据还可以提供有关FASD病理生理学的重要信息，这些信息反过来可以有助于开发更好地针对这种疾病特征的特定缺陷的治疗方法。

DESCRIPTION (provided by applicant): Research on and treatment of fetal alcohol spectrum disorder (FASD) have been hampered by a lack of specificity in behavioral diagnostic criteria and limited understanding of the neural substrates that mediate the observed cognitive deficits. Previous studies have identified arithmetic as a particularly sensitive developmental endpoint in FASD. Data from our Detroit cohort suggest that fetal alcohol-related impairment in arithmetic is mediated by a specific deficit in the core quantity system involving the ability to mentally represent and manipulate number, which has been linked to alcohol-related deficits in parietal lobe function in neuroimaging studies. This deficit appears to be evident already in infancy, as indicated by pilot data from our Cape Town cohort suggesting poorer performance by alcohol-exposed infants on the Wynn numerosity paradigm. It is not clear, however, whether impaired performance on this paradigm reflects a specific deficit in representation of quantity; a deficit in error detection, an aspect of execution function that has also been reported in alcohol- exposed children; or more general perceptual or cognitive impairment in the exposed infants. The event-related potentials (ERP) technique provides a unique opportunity to collect precise information regarding the time course and specific components of information processing that can advance understanding of the specific deficits in number processing and error detection in alcohol-exposed infants seen in the Wynn paradigm. 50 infants, whose mothers will have been recruited in mid-pregnancy, will be studied at 6 months postpartum- 25 heavy exposed and 25 non-exposed controls, matched for maternal education and gestational age when antenatal care was initiated. The aims are (1) to confirm that the adverse effect of fetal alcohol exposure on number processing can be detected behaviorally in infancy using the Wynn numerosity paradigm; (2) to use ERP to specify which stages and components of numerosity processing are affected by fetal alcohol exposure in this paradigm-magnitude representation, error monitoring, or both; (3) to use a novel ERP task to determine whether the alcohol-related numerosity deficit seen in the Wynn paradigm is specific to the abstract representation of small quantities rather than perceptual features of the stimulus display that tend to covary with numerosity (e.g., density, total surface area). The proposed study will be conducted in Cape Town, South Africa, where there is an unusually high incidence of alcohol abuse and dependence in women of child-bearing age and the incidence of fetal alcohol syndrome is among the highest in the world. Cape Town is a highly cost-effective venue in which to conduct this study given the unusually large pool of heavily exposed infants available at a single site, the ongoing recruitment of an infant sample for a currently-funded R01 grant who can participate in this study, and the availability of a 128-channel Electrical Geodesics, Inc., system to acquire the ERP data. PUBLIC HEALTH RELEVANCE: Fetal alcohol syndrome (FAS) and other alcohol-related disorders are an important health problem worldwide and a major public health issue in South Africa. The long-term effects of these disorders include significant neurocognitive and behavioral impairment. This proposed ERP study will provide an opportunity to examine brain function in relation to two promising neurocognitive biomarkers of fetal alcohol spectrum disorder (FASD)- numeric magnitude comparison and error detection-very early in development. The identification of biomarkers can improve FASD diagnosis by grounding it in specific aspects of central nervous system function that can be linked biologically to fetal alcohol exposure. Given this link to specific neural pathways, these data can also provide important information about the pathophysiology of FASD, which can, in turn, contribute to the development of treatments that are better targeted to the specific deficits that characterize this disorder.