Neural Substrates of Executive Function: An fMRI Twin Study

执行功能的神经基质：功能磁共振成像双胞胎研究

• 批准号: 9211378
• 负责人: Naomi P. Friedman
• 金额: $ 68.02万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-01 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9211378
• 关键词: Address; Adult; Age; Area; Attention; Attention deficit hyperactivity disorder; Base of the Brain; Behavior; Behavior Disorders; Behavioral; Behavioral Genetics; Birth; Brain; Categories; Clinical; Colorado; Complex; Data; Development; Dimensions; Disease; Elements; Emotional disorder; Environmental Risk Factor; Etiology; Functional Magnetic Resonance Imaging; Funding; Genetic; Genetic Models; Genetic Predisposition to Disease; Genetic Structures; Genetic study; Goals; Health; Heritability; Image; Individual; Individual Differences; Interview; Investigation; Knowledge; Lead; Link; Literature; Measures; Mediating; Mental Depression; Mental Health; Mental disorders; National Institute of Mental Health; Neurosciences Research; Obsessive-Compulsive Disorder; Occupations; Participant; Performance; Phenotype; Phonation; Pilot Projects; Population; Positioning Attribute; Problem behavior; Process; Psychopathology; Questionnaires; Recruitment Activity; Research; Research Domain Criteria; Risk Factors; Role; Sampling; Sampling Studies; Schizophrenia; Self-Direction; Short-Term Memory; Structure; Symptoms; Telephone; Testing; Twin Multiple Birth; Twin Studies; Update; Variant; Wages; base; behavioral study; cognitive control; design; executive function; experience; externalizing behavior; imaging study; independent component analysis; indexing; infancy; mental set; neural circuit; neuroimaging; public health relevance; relating to nervous system; response; task analysis; trait

DESCRIPTION (provided by applicant): It is highly plausible that heritable individual differences in executive functions (EFs), mediated by variation in identifiable neural circuits, contribute to a generalized genetic vulnerability to psychopathology and psychiatric disorder. Determining the extent to which functional variation in neural circuits supporting EF is itself heritable, or influenced by environmental factors, will provide information critical to understanding the role of neural circuits in mediating the genetic and environmental vulnerability to mental illness. In this competitive renewal, we propose to extend our twin study of individual differences in EFs by conducting the following: (1) the first large-scale functional magnetic resonance imaging (fMRI) study of individual differences in the multiple EFs; (2) the first fMRI study of EFs to incorporate latent variables measured outside of the scanner; and (3) the first behavior genetic study of functional neural indices of these multiple EFs in adulthood. By collecting fMRI data on a carefully selected set of EF tasks and analyzing it in conjunction with additional EF tasks measured outside the scanner, as well as new assessments of psychopathology linked to EFs, we will be able to determine neural circuits related to individual differences in EFs and associated psychopathology. Because the data come from twins, we will also assess the genetic and environmental etiologies of individual differences in these neural indices, and examine their genetic and environmental correlations with the behavioral EF measures. Finally, by integrating the neural data with assessments of symptoms related to psychopathology (e.g., attention problems, depression), we will test whether the brain areas related to EFs mediate the relations between EFs and these symptoms identified in this sample. To achieve these aims we conduct an fMRI study on twins who have participated in the Colorado Longitudinal Twin Study (LTS) since infancy and have previous EF assessments. Based on recruitment rates for prior waves and a pilot study, we estimate 640 participants from 320 twin pairs (167 monozygotic and 153 dizygotic). In the scanner they will perform 3 tasks tapping 3 separable but correlated EFs: inhibiting prepotent responses, updating working memory, and shifting between tasks or mental sets. They will complete 3 additional EF tasks outside the scanner so we can construct latent variables for each component. They will also complete phone interviews and online questionnaire assessments of symptoms related to mental illness before the imaging session. We will analyze the imaging data using independent components analysis to identify separable neural circuits that correlate with individual differences in performance. We will then examine whether these neural measures mediate the relations between EFs and symptoms of psychopathology.

描述（由申请人提供）：执行功能（EF）的遗传性个体差异（由可识别神经回路的变异介导）导致精神病理学和精神疾病的广义遗传易感性，这是非常合理的。确定支持EF的神经回路中的功能变异本身是可遗传的或受环境因素影响的程度，将为理解神经回路在介导遗传和环境对精神疾病的脆弱性中的作用提供关键信息。在这次竞争性更新中，我们建议通过以下方式扩展我们对EFs个体差异的双胞胎研究：（1）首次对多种EFs的个体差异进行大规模功能磁共振成像（fMRI）研究;（2）首次对EFs进行fMRI研究，以纳入扫描仪外测量的潜在变量;（3）首次对这些多个EFs成年期的神经功能指标进行了行为遗传学研究。通过收集一组精心挑选的EF任务的fMRI数据，并结合扫描仪外测量的其他EF任务以及与EF相关的精神病理学的新评估进行分析，我们将能够确定与EF和相关精神病理学的个体差异相关的神经回路。由于数据来自双胞胎，我们还将评估这些神经指标个体差异的遗传和环境病因，并通过行为EF测量来检查它们的遗传和环境相关性。最后，通过将神经数据与与精神病理学相关症状的评估（例如，注意力问题，抑郁症），我们将测试与EF相关的大脑区域是否介导EF与该样本中鉴定的这些症状之间的关系。为了实现这些目标，我们进行了一项功能磁共振成像研究的双胞胎谁参加了科罗拉多纵向双胞胎研究（LTS），从婴儿期开始，并有以前的EF评估。根据招募率前波和试点研究，我们估计640名参与者从320对双胞胎（167同卵和153异卵）。在扫描仪中，他们将执行3个任务，利用3个可分离但相关的EF：抑制优势反应，更新工作记忆，以及在任务或心理设置之间转换。他们将在扫描仪外完成3个额外的EF任务，因此我们可以为每个组件构建潜在变量。他们还将在成像会议之前完成与精神疾病相关症状的电话采访和在线问卷评估。我们将使用独立成分分析来分析成像数据，以识别与个体表现差异相关的可分离神经回路。然后，我们将研究是否这些神经措施调解EF和精神病理学症状之间的关系。