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

项目概要/摘要 酒精使用是一个全球性的健康问题，通常始于青春期/青年期。尽管进行了广泛 研究工作、有效的预防和治疗措施仍然遥遥无期。虽然双向关联 酒精使用和大脑功能之间的联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然没有得到充分的研究。5年K99/R 00 该提案旨在通过切割的新应用来解决这一根本性的知识差距， 边缘技术克服了受试者间横截面设计的许多限制，包括 低可靠性和小效应量。据推测，决策的神经认知机制， 青春期潜在的高风险行为（即，相对于较低的认知控制，奖励处理水平提高） 有助于青少年开始饮酒，以及年轻人的升级和维持， 酒精的消费反过来影响这些相同的机制，从而促进未来的使用。 至关重要的是，该提案旨在通过以下方式支持申请人向独立过渡：1）技术 培训先进的纵向和机器学习分析，并收集和分析精度 功能映射（PFM）数据，2）年轻人酒精使用行为评估培训，以及3） 专业和职业发展，包括领导力和导师制， 网络、出版物和科学报告。目标1（K99）将评估预期的长期关联 在青少年和年轻人的两个大的现存数据集中， （IMAGEN：14-22岁，N=2000; ABCD：9-18岁，N= 11，000）。分析将使用多变量神经签名 这些过程中，这是更可靠的和敏感的个人差异比区域估计。旨在 2&3（K99/R 00）将收集小说ALC-21样本-从事重 间歇性饮酒（N=24），将在一个学期内立即重复扫描（每次扫描8-10次） 在大量使用之后（例如，21岁生日）和减少使用。精确功能映射的使用 (PFM)- 通过采集大量的成像数据，研究具有大的受试者内变化的效果， 受试者-最大化神经成像信号、空间分辨率和测量可靠性。PFM导致 强大而可靠的主体内脑行为关联。将采集完整样本的子集（N=5） 目标2，并将用于测试大量间歇性饮酒对奖励和认知的短期影响。 控制剩余样本将在目标3的R 00部分采集，该部分将评估 奖励，认知控制和酒精使用之间的定向短期关联。这些研究一起 将为酒精使用和大脑功能之间的相互关系提供基本的见解， 无论是长期的还是短期的此外，完成本培训计划将使申请人做好领导 作为一名独立的研究者进行一项创新的研究计划。

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.