Neural Substrates of Executive Function: An fMRI Twin Study

描述(由申请人提供)：执行功能(EFS)的可遗传个体差异，由可识别的神经回路的变化调节，极有可能导致精神病理学和精神障碍的普遍遗传脆弱性。确定支持EF的神经回路的功能变异在多大程度上是可遗传的，或受到环境因素的影响，将提供至关重要的信息，以了解神经回路在调节遗传和环境对精神疾病的易感性中的作用。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)首次对多个EFS的个体差异进行大规模功能磁共振成像(FMRI)研究；(2)首次将扫描仪外测量的潜在变量纳入EFS的fMRI研究；以及(3)首次对成年后这些多个EFS的功能神经指数进行行为遗传学研究。通过收集一组精心选择的EF任务的fMRI数据，并结合在扫描仪外测量的其他EF任务以及与EFS相关的新的精神病理学评估进行分析，我们将能够确定与EFS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数中个体差异的遗传和环境原因，并使用行为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的症状(例如注意力问题、抑郁)的评估相结合，我们将测试与EFS相关的大脑区域是否在EFS与本样本中确定的这些症状之间的关系中起到中介作用。为了实现这些目标，我们对从婴儿时期就参加了科罗拉多州纵向双胞胎研究(LTS)并有先前的EF评估的双胞胎进行了功能磁共振研究。基于先前WAVE和一项先导性研究的招募比率，我们估计来自320对双胞胎的640名参与者(167对同卵和153对异卵)。在扫描仪中，他们将利用三个可分离但相关的EFS执行三项任务：抑制优势反应，更新工作记忆，以及在任务或心理状态之间切换。他们将在扫描仪外完成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。他们还将在成像课程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。我们将使用独立分量分析来分析成像数据，以确定与个体表现差异相关的可分离神经回路。然后，我们将检查这些神经测量是否在EFS和精神病理症状之间的关系中起中介作用。

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.