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.
: 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.
