Adolescent Maturation of Brain Network Integration for Executive Control Abilitie

描述(申请人提供)：青春期是一个不同的发展阶段，在此期间，对行为和认知的“执行”控制在神经心理测试中提高到成熟的成人水平。已有研究提出，这些认知能力的提高是神经专门化程度不断提高的结果，也是许多从事任务执行的功能化专门化脑区功能整合的结果。这种想法通常被称为神经建构主义，它预测青春期认知能力的不断完善主要是通过大脑区域参与功能定义的网络的经验变化来完成的。尽管之前的许多神经成像研究发现，大脑结构和活动水平与年龄相关的变化与神经建构主义理论的预测一致，但还没有对这一假设进行直接测试。具体地说，还没有研究直接检查功能连接性随年龄的变化，以证实在整个青春期参与任务的大脑区域的整合增加。此外，在典型的青少年发展过程中，大脑活动和执行测试成绩变化之间的关系几乎没有得到研究。大脑系统功能的“生成性”模型强调有效的区域间连接和网络交互对于最佳认知功能的重要性。这些模型是基于令人信服的证据，即大脑系统是按等级组织的，因此更高级别的系统(包括历史上公认的额叶执行脑区)对下属神经系统施加自上而下的控制。这一神经模型与执行者认知能力的假设组织是一致的，后者通常被认为是由监督或以其他方式影响附属认知操作的高级认知功能组成的。然而，由于大脑功能连通性的研究还处于初级阶段，人们从未探索过所谓的自上而下的神经系统影响与更高级别的执行认知之间的可能对应关系。这是为最近资助的R01提交的竞争性修订，目的是研究这些主题。我们将进行一项为期5年的横断面研究(n=130)，研究对象为正常的青少年到青壮年(12-24岁)。母项目将研究三种行为可分离的执行能力背后的功能整合和等级自上而下影响的年龄相关变化。它将测试特定的理论指导的假设，以确定在青春期成熟过程中大脑区域更大程度地相互作用以改善执行控制的各种方式。由于人们日益认识到广泛分布的、功能集成的神经网络在复杂认知中的重要性，该项目将首次对执行功能背后的神经功能连通性进行系统评估。在本补充资料中，我们申请资金将我们样本的扩散张量成像(DTI)评估添加到项目中，以量化解剖连接的发育变化。我们还将收集“静息状态”功能磁共振成像扫描，以便能够扩展查看与执行功能磁共振任务相关的功能连接，以及与我们的静息状态/DTI扫描档案数据库分析相关的功能连接。最重要的是，我们将把DTI数据整合到一个有效的测量模型中，该模型试图确定成熟的功能和解剖连接对认知发展的影响。通过将DTI添加到资助项目的分析框架中，我们希望极大地扩展我们的研究速度和理论影响。 与公共健康相关：尽管“执行”认知功能受损与青春期经常出现的多种精神障碍的风险有关，但对这些复杂认知能力的神经基础了解不足。该项目将首次对执行控制大脑行为关系进行大规模研究，使用网络功能整合的功能神经成像、认知测试以及脑体积和脑白质连通性的成像来描述与成人水平的认知能力正常发展相关的神经生物学变化。除了澄清许多关于执行控制发展的悬而未决的问题外，该项目提供的信息还将有助于未来的临床神经科学研究，这些研究试图更好地了解导致精神疾病的认知风险因素。

DESCRIPTION (provided by applicant): Adolescence is a distinct developmental period during which 'executive' control over behavior and cognition improves towards mature, adult levels of performance on neuropsychological tests. It has been proposed that these cognitive gains are the product of increasing neural specialization and functional integration of numerous functionally-specialized brain regions that are engaged for task performance. This idea is often termed 'neural constructivism,' which predicts that ongoing refinement of cognitive abilities present by puberty is accomplished largely by experience-dependent changes in how brain regions participate in functionally-defined networks. Although many previous neuroimaging studies have found age-related changes in brain structure and activity levels that are consistent with neural constructivist theory predictions, there has been no direct test of this hypothesis. Specifically, no study has directly examined functional connectivity changes with age to confirm increasing integration of task-engaged brain regions throughout adolescence. Moreover, the relationship between brain activity and executive test performance changes during typical adolescent development is virtually unexamined. 'Generative' models of brain system function emphasize the importance of efficient inter-regional connectivity and network interaction for optimal cognitive function. These models are based on compelling evidence that brain systems are hierarchically-organized, such that 'higher-order' systems (which include historically-recognized frontal lobe executive brain regions) exert top-down control over subordinate neural systems. This neural model is consistent with the putative organization of executive cognitive abilities, which are commonly proposed to consist of a higher-order cognitive functions that supervise or otherwise influence subsidiary cognitive operations. However, because the study of brain functional connectivity is in its infancy, the probable correspondence between supposed 'top down' neural system influence and higher-order executive cognition has never been explored. This is a competitive revision submitted for a recently funded R01 to study these topics. We will conduct a 5-year, cross-sectional study (n=130) of normal adolescent to young adult development (ages 12-24). The parent project will examine age-related changes in functional integration and hierarchical top-down influence underlying three behaviorally-dissociable types of executive ability. It will test specific theory-guided hypotheses to determine the various ways brain regions more greatly interact throughout adolescent maturation to produce improvements in executive control. Because of the increasing recognition of the importance of widely-distributed, functionally-integrated neural networks in complex cognition, this project will conduct the first systematic assessment of neural functional connectivity underlying executive function. In this supplement, we request funds to add diffusion tensor imaging (DTI) assessment of our sample to the project to permit quantification of developmental changes in anatomical connectivity. We also will collect 'resting state' fMRI scans to permit an expanded look at functional connectivity relative to the executive fMRI tasks, and relative to an analysis of our archival database of resting state/DTI scans. Most importantly, we will integrate the DTI data into a working measurement model that seeks to determine the influence of maturing functional and anatomical connectivity on cognitive development. By adding DTI within the analytic framework of the funded project, we hope to greatly extend the pace and theoretical impact of our research. PUBLIC HEALTH RELEVANCE : Although impairment in 'executive' cognitive functions is associated with risk for numerous psychiatric disorders that often arise in adolescence, there is insufficient understanding of the neural basis for these complex cognitive abilities. This project will provide the first large-scale study of executive control brain behavior relationships using functional neuroimaging of network functional integration, cognitive testing, and imaging of brain volume and white matter connectivity to depict neurobiological changes associated with normal development of 'adult-level' cognitive ability. In addition to clarifying numerous unanswered questions about the development of executive control, the information provided by this project will benefit future clinical neuroscience studies seeking to better understand cognitive risk factors that contribute to psychiatric illness.