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）：关于胎儿酒精谱系障碍（FASD）的研究和治疗因行为诊断标准缺乏特异性以及对介导观察到的认知缺陷的神经底物的理解而受到阻碍。先前的研究已将算术确定为FASD中特别敏感的发育终点。来自底特律队列的数据表明，算术中与胎儿酒精相关的损伤是由核心数量系统中的特定缺陷介导的，核心数量系统的特定缺陷涉及在神经成像研究中与核心相关的缺陷有关的能力，这与酒精相关的缺陷有关。正如我们开普敦队列的试点数据表明，这种赤字似乎已经在婴儿期，表明在Wynn数字范式上，酒精暴露的婴儿的表现较差。但是，尚不清楚该范式的性能受损是否反映了数量表示的特定缺陷；错误检测的赤字，在酒精暴露的儿童中也报道了执行功能的一个方面；或在暴露的婴儿中更普遍的感知或认知障碍。与事件相关的电位（ERP）技术提供了一个独特的机会，可以收集有关时间过程和信息处理的特定组成部分的精确信息，这些信息可以提高对Wynn Paradigm中酒精暴露婴儿的数量处理和错误检测的特定缺陷的了解。有50名婴儿将在怀孕中期招募的母亲，将在产后6个月 - 25个重度暴露和25个非暴露对照中进行研究，并在启动产前护理时与孕产妇教育和妊娠年龄相匹配。目的是（1）确认使用Wynn数字范式在婴儿期行为可以检测到胎儿酒精暴露对数量处理的不利影响； （2）使用ERP来指定在此范式 - 数字表示，错误监测或两者兼而有之的数字处理的阶段和成分受胎儿酒精暴露的影响； （3）使用新颖的ERP任务来确定在Wynn范式中看到的与酒精相关的数值不足是特定于少量的抽象表示，而不是刺激显示的感知特征，这些特征倾向于具有数值（例如，密度，密度，总表面积）。拟议的研究将在南非开普敦进行，在那里，育儿妇女的酗酒和依赖性异常高，胎儿酒精综合症的发生率是世界上最高的。开普敦是一个高度具有成本效益的场所，鉴于单个站点上有异常大的暴露于暴露的婴儿，持续招募婴儿样本的众多婴儿可以参与这项研究，并且可以使用128个渠道电气的Geodesics，Inc.，Symems.SymeryP Data。 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全球重要的健康问题，也是南非的主要公共卫生问题。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研究将提供一个相对于两个有希望的神经认知生物标志物的胎儿酒精谱系障碍（FASD） - 数字幅度幅度比较和错误检测 - 在发育早期，数值幅度的比较和错误检测。生物标志物的鉴定可以通过将其与胎儿酒精暴露相关的中枢神经系统功能的特定方面来改善FASD诊断。鉴于与特定神经途径的这种联系，这些数据还可以提供有关FASD病理生理学的重要信息，而FASD的病理生理学又可以促进更好地针对表征该疾病的特定缺陷的治疗方法的发展。