Longitudinal Analysis of Diffusion Tensor Imaging to Discover Adolescent Alcohol Use Effect

弥散张量成像纵向分析青少年饮酒效应 项目摘要 酗酒是美国第三大可预防的死亡原因。酒精的标志性伤害 使用障碍（AUD）存在于白质（WM）微观结构及其成分中，这些成分使连接成为可能 近端和远端大脑结构和功能整合的关系。尽管在理解上取得了进展 虽然酒精对成人的影响，但WM成熟异常与启动之间的因果关系尚不清楚 在青春期大量饮酒但不依赖酒精深入了解区域发展， 国家酒精和青少年神经发育联盟（NCANDA）， 831名青少年正常和酒精相关异常神经发育的前瞻性纵向研究 轨迹，每年采集弥散张量成像（DTI）数据。从复杂的酒精效应 青少年神经发育的动态过程需要高度敏感的分析方法。在这个项目中， 我提出了一种新型的纵向DTI分析，其中一个统一的轨迹模型，用于明确 捕获每例受试者访视期间DTI测量值的生物学合理变化， 估计群体水平的发展轨迹。这种方法将导致纵向一致的DTI 测量能够准确表征正常青少年的微结构发育。 基于这种方法，我将测试的假设，即饮酒的前兆发病和中断的影响 由开始使用酒精引起的大脑活动与不同的大脑区域有关。分析将确定 前体通过比较发展轨迹之前，饮酒发作之间的无到低和重 饮酒队列，并将通过比较饮酒开始后的轨迹来确定中断。酒精- 对WM成熟的诱导性破坏将进一步根据年龄分层，突出强调 青少年的脆弱性。最后，拟议的纵向分析也有助于进一步跟踪 微结构重建后戒酒，以确定可逆性或持续性酒精相关损伤。 揭示与青少年大量饮酒有关的成像表型可以指出潜在的原因， AUD的前体，这反过来可以改善临床环境中的诊断和预防。此外，委员会认为， 研究人员将能够使用拟议的纵向方法作为一种通用工具来回答他们的问题。 在寻求发展变化的背景下的神经科学问题。

Longitudinal Analysis of Diffusion Tensor Imaging to Discover Adolescent Alcohol Use Effect PROJECT ABSTRACT Alcohol abuse is the third leading preventable cause of death in the United States. A signature injury of Alcohol Use Disorder (AUD) is in the white-matter (WM) microstructure and its constituents, which enable connectivity of proximal and distal brain structures and functional integration. Despite the progress in understanding alcohol’s effects in adults, still unclear is the causal direction between abnormal WM maturation and initiation of heavy yet non-dependent drinking during adolescence. To gain insight into regional development of connectivity, the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA), a prospective longitudinal study of 831 youth to track normal and alcohol-related deviant neurodevelopmental trajectories, acquired diffusion tensor imaging (DTI) data annually. Unraveling alcohol effects from the complex dynamic course of adolescent neurodevelopment requires highly sensitive analysis approaches. In this project, I propose a new type of longitudinal DTI analysis, in which a unified trajectory model is used both for explicitly capturing biologically-plausible variation in DTI measurements across visits within each subject and for estimating a group-level developmental trajectory. Such an approach will result in longitudinally consistent DTI measurements enabling accurate characterization of microstructural development in normal adolescents. Based on this approach, I will test the hypothesis that precursors of drinking onset and the disruption effects induced by initiation of alcohol use are related to different brain regions. The analysis will identify the precursors by comparing developmental trajectories prior to drinking onset between the no-to-low and heavy drinking cohorts and will identify the disruption by comparing trajectories after drinking onset. The alcohol- induced disruption to WM maturation will be further stratified with respect to age, highlighting the heightened vulnerability in younger adolescents. Lastly, the proposed longitudinal analysis also facilitates further tracking of microstructural remodeling following abstinence to identify reversible or persistent alcohol-related injury. Revealed imaging phenotypes linked to adolescent heavy drinking could point to potential causes and precursors of AUD, which could in turn improve diagnosis and prevention in clinical settings. Moreover, researchers will be able to use the proposed longitudinal approach as a general tool to answer their neuroscientific questions in the context of seeking developmental change.