Neural Bases of Eyeblink Conditioning in FASD

FASD 眨眼条件反射的神经基础

• 批准号: 7384362
• 负责人: SANDRA W. JACOBSON
• 金额: $ 58.3万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-15 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7384362
• 关键词: 11 year old; Affect; Age; Age-Years; Alcohol abuse; Alcohol-Related Neurodevelopmental Disorder; Alcohols; Algorithms; Animal Model; Area; Atlases; Back; Behavioral; Biological Assay; Biological Markers; Blinking; Brain; Cell Nucleus; Cerebellar Nuclei; Cerebellum; Characteristics; Child; Childhood; Cognitive; Cognitive deficits; Cohort Studies; Collaborations; Color; Communities; Condition; Conditioned Stimulus; Consultations; Corpus Callosum; Data; Data Reporting; Dependence; Depth; Development; Diagnosis; Diagnostic; Differential Diagnosis; Diffusion Magnetic Resonance Imaging; Discrimination; Disease; Dysmorphology; Early Diagnosis; Early Intervention; Early identification; Effect Modifiers (Epidemiology); Elements; End Point; Esters; Etiology; Exhibits; Exposure to; Face; Fatty Acids; Female of child bearing age; Fetal Alcohol Exposure; Fetal Alcohol Spectrum Disorder; Fetal Alcohol Syndrome; Fingers; Follow-Up Studies; Functional Magnetic Resonance Imaging; Functional disorder; Genetic Polymorphism; Goals; Gold; Growth; Head circumference; Human; Image; Impaired cognition; Impairment; Incidence; Individual; Infant; Inferior; Institutes; International; Intervention; Interview; Laboratory Animals; Lead; Learning; Life; Link; Lip structure; Lobe; Longitudinal Studies; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Maternal Age; Meconium; Mediating; Movement; Neuraxis; Neurosciences; Numbers; Outcome; Parietal; Parietal Lobe; Pathway interactions; Pattern; Performance; Personal Satisfaction; Phenotype; Pilot Projects; Postpartum Period; Pregnancy; Process; Psychological reinforcement; Public Health; Purpose; Range; Recording of previous events; Recruitment Activity; Research; Research Personnel; Resolution; Rodent; Sampling; Science; South Africa; Specialist; Specificity; Specimen; Standards of Weights and Measures; Stimulus; Structure; Symptoms; Techniques; Testing; Time; TimeLine; Universities; Variant; Visual Acuity; alcohol consumption during pregnancy; alcohol effect; alcohol exposure; base; brain morphology; caudate nucleus; cohort; conditioning; craniofacial; design; drinking; efficacy evaluation; follow-up; human study; improved; infancy; innovation; interest; intrapartum; neural circuit; neurobehavioral; neuroimaging; neuropathology; neuropsychological; prenatal exposure; processing speed; prospective; relating to nervous system; response; tool; white matter

DESCRIPTION (provided by applicant): Diagnosis of fetal alcohol spectrum disorder (FASD) is difficult because information regarding prenatal exposure is often lacking, many affected children do not exhibit the characteristic facial anomalies, and no distinctive behavioral phenotype has been identified. Development of appropriate treatments has been hampered by limited understanding of the pathophysiology of FASD. Since 1999, we have been conducting a prospective, longitudinal study in the Cape Coloured (mixed ancestry) community in Cape Town, South Africa, where there is an exceptionally high incidence of fetal alcohol syndrome (FAS). In a 5-year follow-up of this cohort, we found a remarkably consistent effect of fetal alcohol exposure on eyeblink conditioning, a cerebellar-dependent form of learning whose neural circuitry and alcohol effects have been documented in detail in laboratory animals; not a single child with full FAS met criterion for conditioning, compared with 75% of the non-exposed controls. Thus, we have identified a potential biomarker of alcohol-related CNS impairment. Moreover, because it is well established in early infancy, short-delay EBC may provide an important tool in the early diagnosis of FASD and in the evaluation of the efficacy of intrapartum and early postpartum interventions. In this study we will follow-up our Cape Town cohort of 165 children at 8.5 years and recruit a new prospective cohort of 60 infants (30 heavy exposed, 30 controls) from the same community. The principal aims are to characterize the developmental course of alcohol-related impairment in EBC; to use selected neuroimaging techniques to examine the impact of fetal alcohol exposure on the neural circuitry mediating EBC; and to use neurobehavioral and functional MRI tasks to assess effects on cerebellar- mediated timing, a central element of EBC. Advanced neuroimaging will include high resolution structural MRI to examine the regional pattern of brain hypoplasia and the first whole brain diffusion tensor imaging (DTI) in children with FASD to assess the integrity of white matter tracts. The moderating effects of maternal age, alcohol abuse history, and variants of the ADH1B polymorphism on the child's vulnerability to FASD will also be examined. Public Health Relevance: A better understanding of the effects of fetal alcohol exposure on the EBC cerebellar circuit in childhood and infancy has the potential to advance our understanding of the neuropathology of FASD, to improve the diagnosis and treatment of this disorder, and to enable earlier identification of affected children.

描述（由申请人提供）：诊断胎儿酒精谱系障碍（FASD）很困难，因为有关产前暴露的信息通常缺乏，许多受影响的儿童没有表现出特征性的面部异常，也没有发现独特的行为表型。对FASD的病理生理学有限的了解，适当治疗的发展受到了阻碍。自1999年以来，我们一直在南非开普敦的Cape Colored（混合血统）社区进行一项前瞻性，纵向研究，那里有一个异常高的胎儿酒精综合症发生率（FAS）。在这一队列的5年随访中，我们发现胎儿酒精暴露对Eykeblink调节的影响非常一致，这是一种依赖小脑的学习形式，其神经回路和酒精效应已在实验室动物中进行了详细记录。没有一个完全FAS的单个孩子满足适应条件的标准，而非暴露对照的75％。因此，我们已经确定了与酒精相关的中枢神经系统损伤的潜在生物标志物。此外，由于它在早期时期已经确定，因此短期EBC可能会在早期诊断FASD以及评估产前和产后早期干预效果的评估中提供重要的工具。在这项研究中，我们将在8.5岁时跟进开普敦队的165名儿童，并从同一社区招募新的60个婴儿（30个沉重暴露，30个对照）。主要目的是表征EBC中与酒精相关的损害的发育过程；使用选定的神经影像技术来检查胎儿酒精暴露对介导EBC的神经回路的影响；并使用神经行为和功能性MRI任务来评估对EBC的中心元素小脑介导的时间的影响。晚期神经影像学将包括高分辨率结构性MRI，以检查FASD儿童中脑发育不全的区域模式和第一个整个脑扩散张量成像（DTI），以评估白质区的完整性。还将检查产妇年龄，酒精滥用历史以及ADH1B多态性对孩子脆弱性FASD的调节作用。公共卫生相关性：更好地理解胎儿酒精暴露对儿童和婴儿期EBC小脑电路的影响，有可能提高我们对FASD神经病理学的理解，以改善对这种疾病的诊断和治疗，并早些时候启用识别受影响的儿童。