Reciprocal longitudinal associations between brain function and alcohol use trajectories in adolescents and young adults

项目摘要/摘要 饮酒是一个全球性的健康问题，通常始于青春期/青春期。尽管广泛 研究努力、有效的预防和治疗措施仍然难以捉摸。而双向关联 酒精使用和大脑功能之间的关系构成了著名的成瘾神经生物学理论的基石， 饮酒和大脑功能之间的相互关系仍未得到充分研究。本5年期K99/R00 该提案旨在通过切割的新应用来解决知识中的这一根本差距-- 边缘技术克服了受试者间横断面设计的许多限制，包括 可靠性低，效果尺寸小。有人假设，决策的神经认知机制 青春期冒险程度不高(即，相对于认知控制力较低的回报处理较高) 有助于在青春期开始饮酒，以及在年轻人中逐步增加和维持饮酒，以及 酒精的消费反过来又会影响这些相同的机制，从而促进未来的使用。 至关重要的是，这项建议旨在通过以下方式支持申请人向独立的过渡：1)技术 高级纵向和机器学习分析方面的培训，以及收集和分析精度 功能图(PFM)数据，2)评估年轻人酒精使用行为的培训，以及3) 专业和职业发展，包括领导力和导师、恩赐精神、专业 网络、出版和科学演示。目标1(K99)将评估未来的长期联系 在青少年和年轻人两个现存的大型数据集中，奖赏、认知控制和酒精使用之间的关系 (图像：14-22岁，N=2000；ABCD：9-18岁，N=11,000)。分析将使用多变量神经信号 与区域估计相比，这些过程对个体差异更可靠、更敏感。目标 2和3(K99/R00)将收集新的ALC-21样本-从事重工的大学生样本 发作性饮酒(N=24)，在一个学期内立即重复扫描(每次扫描8-10次) 在使用量增加(例如，21岁生日)和使用量减少之后。精准功能图的使用 (PFM)-通过获取每个对象的大量成像数据来研究对象内部变化较大的效果 受试者-最大化神经成像信号、空间分辨率和测量可靠性。PFM结果为 健壮可靠的受试者内部大脑行为关联。将收集完整样本(N=5)的子集 用于目标2，并将用于测试大量饮酒对奖赏和认知的短期影响 控制力。剩余的样本将在R00部分为AIM 3收集，该部分将评估BI- 奖励、认知控制和饮酒之间的定向短期联系。总而言之，这些研究 将提供对饮酒和大脑功能之间相互关系的基本见解，两者都 从长期和短期来看。此外，完成此培训计划将使申请者为领导做好准备 作为独立调查员的创新研究项目。

PROJECT SUMMARY/ABSTRACT Alcohol use is a global health problem that often begins in adolescence/young adulthood. Despite extensive research efforts, effective preventative and treatment measures remain elusive. While bi-directional associations between alcohol use and brain function form the cornerstone of prominent neurobiological theories of addiction, the reciprocal relationship between alcohol use and brain function remains underexplored. This 5-year K99/R00 proposal is designed to address this fundamental gap in knowledge, through the novel application of cutting- edge techniques which overcome many of the limitations of between-subject cross-sectional designs, including low reliability and small effect sizes. It is hypothesized that neurocognitive mechanisms of decision making which underly elevated risk taking in adolescence (i.e., elevated reward processing relative to lower cognitive control) contribute to alcohol use initiation in adolescence, as well as escalation and maintenance in young adults, and that the consumption of alcohol in turn influences these same mechanisms, thereby promoting future use. Crucially, this proposal is designed to support the applicant’s transition to independence through: 1) technical training in advanced longitudinal and machine learning analysis, and the collection and analysis of precision functional mapping (PFM) data, 2) training in assessments of alcohol use behavior in young adults, and 3) professional and career development, including leadership and mentorship, grantsmanship, professional networking, publication, and scientific presentations. Aim 1 (K99) will assess prospective long-term associations between reward, cognitive control, and alcohol use in two large extant datasets of adolescents and young adults (IMAGEN: ages 14-22, N=2000; ABCD: ages 9-18, N=11,000). Analyses will use multivariate neural signatures of these processes, which are more reliable and sensitive to individual differences than regional estimates. Aims 2&3 (K99/R00) will collect the novel ALC-21 sample – a sample of college students who engage in heavy episodic drinking (N=24), who will be scanned repeatedly (8-10 scans each) over a semester, immediately following periods of elevated use (e.g., 21st birthday) and reduced use. The use of precision functional mapping (PFM) – studying an effect with large within-subject variation by acquiring large quantities of imaging data per subject – maximizes the neuroimaging signal, spatial resolution, and measurement reliability. PFM results in robust and reliable within-subject brain-behavior associations. A subset of the full sample (N=5) will be collected for Aim 2, and will be used to test the short-term effect of heavy episodic drinking on reward and cognitive control. The remainder of the sample will be collected during the R00 portion for Aim 3, which will assess bi- directional short-term associations between reward, cognitive control, and alcohol use. Together, these studies will provide fundamental insights into the reciprocal relationship between alcohol use and brain function, both over the long-term and in the short-term. Further, completing this training plan will prepare the applicant to lead an innovative research program as an independent investigator.