Neural Substrates of Executive Function: An fMRI Twin Study

描述（由申请人提供）：由可识别的神经回路变异介导的执行功能（EFs）的遗传个体差异，导致了精神病理和精神障碍的普遍遗传易感性，这是非常可信的。确定支持EF的神经回路的功能变异在多大程度上是遗传的，或受环境因素的影响，将为理解神经回路在介导对精神疾病的遗传和环境脆弱性方面的作用提供关键信息。在这一竞争更新中，我们建议通过以下方式来扩展我们的双孪生研究：(1)首次大规模功能性磁共振成像（fMRI）研究多个电磁场的个体差异；(2)第一个将扫描外测量的潜在变量纳入EFs的fMRI研究；(3)首次在成年期对这些多发性EFs的功能神经指标进行行为遗传学研究。通过收集精心挑选的EF任务的fMRI数据，并将其与扫描仪外测量的额外EF任务以及与EF相关的精神病理的新评估相结合进行分析，我们将能够确定与EF个体差异和相关精神病理相关的神经回路。由于数据来自双胞胎，我们还将评估这些神经指数个体差异的遗传和环境病因，并检查它们与行为EF测量的遗传和环境相关性。最后，通过将神经数据与精神病理学相关症状（例如，注意力问题、抑郁）的评估相结合，我们将测试与电磁场相关的大脑区域是否介导了电磁场与本样本中确定的这些症状之间的关系。为了实现这些目标，我们对从婴儿期开始参加科罗拉多纵向双胞胎研究（LTS）并进行过EF评估的双胞胎进行了功能磁共振成像研究。根据前几波的招募率和一项试点研究，我们估计有640名参与者来自320对双胞胎（167对同卵双胞胎和153对异卵双胞胎）。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EFs：抑制优势反应，更新工作记忆，以及在任务或思维模式之间转换。它们将在扫描仪之外完成3个额外的EF任务，这样我们就可以为每个组件构建潜在变量。他们还将在影像学检查前完成电话访谈和与精神疾病相关症状的在线问卷评估。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，我们将研究这些神经测量是否介导了电磁场与精神病理症状之间的关系。

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.