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

青少年饮酒效应的弥散张量成像纵向分析 项目摘要 在美国，酗酒是第三大可预防的死亡原因。酒精的标志性损伤 使用障碍(AUD)存在于白质(WM)微结构及其成分中，这使连接成为可能 近端和远端的大脑结构和功能整合。尽管在理解方面取得了进展 酒精对成人的影响，尚不清楚白质成熟异常与启动之间的因果关系 在青春期大量但不依赖饮酒。深入了解……区域发展 连接性，国家酒精与青春期神经发育联盟(NCANDA)，a 831名青年追踪正常和酒精相关异常神经发育的前瞻性纵向研究 轨迹、每年获得的扩散张量成像(DTI)数据。从复合体中解开酒精的影响 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， 我提出了一种新的纵向DTI分析，其中使用统一的轨迹模型来显式地 在每个受试者和受试者的访问中捕捉DTI测量的生物学上可信的差异 估计群体水平的发展轨迹。这样的方法将产生纵向一致的DTI 这些测量能够准确地描述正常青少年的微结构发育。 基于这种方法，我将检验以下假设：饮酒的前兆开始和干扰效应 开始饮酒所诱发的脑区与不同的脑区有关。该分析将确定 通过比较不饮酒到低饮酒和重度饮酒患者在饮酒前的发育轨迹来确定前体 并将通过比较饮酒开始后的轨迹来识别中断。酒精- 对WM成熟的诱导中断将根据年龄进一步分层，突出显示 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 戒酒后微结构重塑的研究，以确定可逆性或持续性酒精相关损伤。 揭示的与青少年酗酒有关的成像表型可能指出潜在的原因和 AUD的前体，这反过来又可以改善临床环境中的诊断和预防。此外， 研究人员将能够使用提议的纵向方法作为通用工具来回答他们的 寻求发展变化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.