An ERP Study of Infant Numerosity in Fetal Alcohol Syndrome

胎儿酒精综合征婴儿数量的 ERP 研究

• 批准号: 8165111
• 负责人: ANDREA BERGER
• 金额: $ 22.63万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8165111
• 关键词: Adverse effects; Affect; Alcohol abuse; Alcohol dependence; Alcohol-Related Disorders; Alcohols; Area; Behavioral; Biological Markers; Blinking; Brain; Caring; Child; Cognitive deficits; Data; Data Collection; Detection; Development; Diagnosis; Diagnostic; Disease; Education; Event-Related Potentials; Female of child bearing age; Fetal Alcohol Exposure; Fetal Alcohol Spectrum Disorder; Fetal Alcohol Syndrome; Functional disorder; Funding; Gestational Age; Grant; Health; Impaired cognition; Impairment; Incidence; Infant; Laboratories; Link; Long-Term Effects; Longitudinal Studies; Mediating; Monitor; Mothers; National Institute on Alcohol Abuse and Alcoholism; Nervous System Physiology; Neural Pathways; Neuraxis; Neurocognitive; Parietal Lobe; Performance; Postpartum Period; Pregnancy; Process; Protocols documentation; Public Health; Recruitment Activity; Reporting; Research; Sampling; School-Age Population; Site; South Africa; Specificity; Staging; Stimulus; Surface; System; Techniques; Time; To specify; Training; Visit; abstracting; alcohol exposure; behavioral impairment; cohort; conditioning; cost; cost effective; density; design; fetal; improved; infancy; information processing; neural circuit; neurobehavioral; neuroimaging; novel; relating to nervous system; therapy development

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.

描述（由申请人提供）：胎儿酒精谱系障碍（FASD）的研究和治疗受到行为诊断标准缺乏特异性和对介导所观察到的认知缺陷的神经底物的有限理解的阻碍。以前的研究已经确定算术是FASD中特别敏感的发育终点。来自底特律队列研究的数据表明，胎儿酒精相关的算术损伤是由核心数量系统中的特定缺陷介导的，该缺陷涉及心理表征和操纵数字的能力，这与神经影像学研究中顶叶功能的酒精相关缺陷有关。这种缺陷似乎在婴儿期就已经很明显了，正如我们的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度范式上的表现较差。然而，尚不清楚这种范式的受损表现是否反映了数量表征的特定缺陷;错误检测的缺陷，这也是酒精暴露儿童中报告的执行功能的一个方面;或者暴露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，收集精确的信息的时间过程和特定组件的信息处理，可以提前了解具体的赤字在数字处理和错误检测中看到的酒精暴露的婴儿在永利范式。将在产后6个月对50名婴儿进行研究，其母亲将在怀孕中期招募，其中25名为重度暴露组，25名为非暴露组，在开始产前护理时，母亲的教育程度和胎龄相匹配。本研究的目的是：（1）证实胎儿酒精暴露对数字加工的不良影响可以在婴儿期用Wynn数字性范式进行行为检测;（2）用ERP确定在Wynn数字性范式中，胎儿酒精暴露对数字性加工的哪些阶段和组成部分--数量表征、错误监控或两者兼而有之--产生影响;（3）使用一种新的ERP任务来确定在Wynn范式中看到的与酒精相关的数字性缺陷是否特定于小数量的抽象表征，而不是倾向于与数字性协变的刺激显示的感知特征（例如，密度、总表面积）。拟议的研究将在南非的开普敦进行，那里的育龄妇女酗酒和依赖的发生率异常高，胎儿酒精综合症的发生率也是世界上最高的。考虑到单个研究中心可获得的重度暴露婴儿样本量异常大，目前正在招募可参与本研究的R 01资助婴儿样本，以及128通道电气大地测量公司的可用性，开普敦是进行本研究的一个极具成本效益的地点，系统获取ERP数据。 公共卫生关系：胎儿酒精综合征（FAS）和其他酒精相关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显著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，以检查大脑功能的两个有前途的神经认知生物标志物的胎儿酒精谱系障碍（FASD）-数字幅度比较和错误检测-非常早期的发展。生物标志物的识别可以通过将其建立在中枢神经系统功能的特定方面来改善FASD的诊断，这些功能可以在生物学上与胎儿酒精暴露相关。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，这反过来又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。