Mapping normal developmental coupling between structural and functional brain networks and abnormalities associated with psychosis

项目摘要 在青春期，人类的大脑经历了显著的结构和功能完善，以支持快速发展。 认知和行为发展。然而，发展白色物质建筑和 和紧急功能连接仍然知之甚少。必须阐明发展 青年人结构-功能耦合的潜在机制，如毁灭性的精神障碍， 精神病与这一时期进化中的大脑连接中断有关。具体地说， 精神病的特征是大脑过程的异常功能整合。这可能导致 从大脑发育过程中白色物质连接的异常布线， 功能可塑性（连接功能相关神经元内的轴突的活性依赖性髓鞘形成） 电路）或两者。 这项提案将把尖端的网络科学和机器学习工具应用于纵向神经成像 和作为费城神经发育队列的一部分获得的丰富的临床表型数据（n=503， 年龄9-25岁），一个大型的基于社区的大脑发育研究。此外，这一目标 建议是（1）系统地描述结构连通性是否推动发展 大脑模块内功能连接的变化，反之亦然，以及（2）识别 结构-功能耦合与精神病谱系症状的纵向负担相关。 这项工作将测试的总体假设，结构连接之前，并推动发展 不同大脑模块内功能连接的变化，进一步说， 结构-功能偶联将与精神病谱系症状负担增加相关。 成功完成所提出的目标将提供关键的新见解，关于典型的大脑 成熟和精神病的神经发育病因学。值得注意的是，不同类型的精神病理学 越来越多地与非典型的大脑成熟有关，这项研究的结果可能会导致更早的 为有精神障碍风险的个人提供诊断和强化治疗。

PROJECT SUMMARY During adolescence, the human brain undergoes marked structural and functional refinements to support rapid cognitive and behavioral development. However, the relationship between developing white matter architecture and emergent functional connectivity remains poorly understood. It is imperative to elucidate developmental mechanisms underlying structure-function coupling in youth, as devastating mental disorders such as psychosis have been linked to the disruption of evolving brain connectivity during this epoch. Specifically, psychosis has been characterized by the anomalous functional integration of brain processes. This could result from the aberrant wiring of white matter connections during brain development, from aberrant processes of functional plasticity (activity-dependent myelination of axons linking neurons within functionally-relevant circuits), or both. This proposal will apply cutting-edge network science and machine learning tools to longitudinal neuroimaging and rich clinical phenotyping data acquired as a part of the Philadelphia Neurodevelopmental Cohort (n=503, ages 9-25 years old), a large community-based study of brain development. Moreover, the goal of this proposal is to (1) systematically characterize whether structural connectivity drives developmental changes in functional connectivity within brain modules, or vice versa, and (2) identify abnormalities of structure-function coupling associated with the longitudinal burden of psychosis spectrum symptoms. This work will test the overarching hypothesis that structural connectivity precedes and drives developmental changes in functional connectivity within distinct brain modules, and further, that the aberrant development of structure-function coupling will be associated with increased burden of psychosis spectrum symptoms. Successful completion of the proposed aims will provide critical new insights regarding both typical brain maturation and the neurodevelopmental etiology of psychosis. Notably, as diverse types of psychopathology are increasingly linked to atypical brain maturation, findings generated by this study could lead to earlier diagnosis and enhanced treatment for individuals at risk for developing mental disorders.