Cortical subcortical reorganization and risk behaviors of early alcohol use initiation

项目摘要/摘要 青春期早期开始饮酒(EIAU)是终生饮酒的关键因素 (AUD)和/或物质使用障碍(SUD)。预防和干预EIAU的一个关键因素是及早 使用行为或认知风险前兆进行检测；更好地了解其潜在的神经 在开始使用药物之前使用底物可能有助于制定更有效和更有针对性的干预措施。 先前的研究表明，睡眠障碍、内化行为、外化行为和认知 绩效是EIAU的潜在风险前兆。然而，已有混合或不一致的研究结果被报道。 这可能反映了研究设计和方法问题，以及共同作用的神经基质。 这些频繁发生的问题的发展情况仍有待确定。在本申请中，我们建议 使用纵向青少年脑认知发展(ABCD)研究的数据来研究神经 预测EIAU及其风险前兆的底物。许多先进的分析方法将 用于在结构和功能两个层次上提取新特征。例如，联合和个人 将使用方差解释(JIVE)方法来提取具有生物学意义的皮质-皮质下协变 模式。现有的文献和我们的初步结果使我们假设，皮质-皮质下 协变模式包括脑干、丘脑、前额叶皮质等区域。 睡眠发育、内化行为、外化行为和认知功能减退 从童年到青春期中期。具体地说，这个项目有三个相辅相成的目标。目标1将评估 基线皮质-皮质下协变模式与EIAU及其四种危险前兆的关系 在青春期中期。目标2将描述皮质-皮质下协变的发展轨迹 在纵向上建立模型并评估其与四种风险前兆的动态关系。目标3将探索 功能连接可预测睡眠障碍、认知表现、行为问题和/或年龄 第一次饮酒。这一应用的结果将极大地推动成瘾神经科学领域的发展。

Project Summary/Abstract Early initiation of alcohol use (EIAU) during adolescence is a key contributor to development of lifetime alcohol (AUD) and/or substance use disorders (SUDs). A critical component for preventing and intervening EIAU is early detection using behavioral or cognitive risk precursors; and understanding better their underlying neural substrates before the onset of substance use may aid in developing more effective and targeted interventions. Prior studies suggest sleep disturbance, internalizing behaviors, externalizing behaviors, and cognitive performance are potential risk precursors of EIAU. However, mixed or inconsistent findings have been reported which may reflect study design and methodological issues, and the neural substrates subserving co- development of these frequently occurring problems remain to be identified. In this application, we propose to use data from the longitudinal Adolescent Brain Cognitive Development (ABCD) study to investigate the neural substrates that are predictive of EIAU and its risk precursors. A number of advanced analytical approaches will be used to extract novel features at both structural and functional levels. For example, the Joint and Individual Variance Explained (JIVE) method will be used to extract biologically meaningful cortical-subcortical covariation patterns. Existing literature and our preliminary results led us to hypothesize that the cortical-subcortical covariation pattern including brainstem, thalamus, prefrontal cortex and other regions underlies the co- development of sleep, internalizing behaviors, externalizing behaviors, and poor cognitive function from late childhood to mid-adolescence. Specifically, this project has three complementary aims. Aim 1 will assess the relationships between the baseline cortical-subcortical covariation patterns and EIAU and its four risk precursors in mid-adolescence. Aim 2 will characterize the developmental trajectory of cortical-subcortical covariation pattern and assess its dynamic relationship with the four risk precursors longitudinally. Aim 3 will explore whether functional connectivity predicts sleep disturbance, cognitive performance, behavioral problems, and/or age at first alcohol use. Results from this application will significantly advance the field of addiction neuroscience.