Neurodevelopment of exploration and alcohol problems in adolescence

项目总结 在青春期探索新奇和陌生的食物、朋友团体和活动，对我们的 成年后的喜好和个性。相反，对于从事未成年饮酒的青少年， 这种对新奇事物的追求可能是不适应的，并导致慢性酒精使用问题的发展。克罗斯- 部分研究表明，个体在使用目标导向的探索时会变得更具战略性 在从青春期过渡到青壮年的过程中优化选择。该理论的核心假设 建议的研究是，定向探索的成熟在以下青少年中迟钝或滞后 尝试饮酒，然后出现更多的饮酒问题。具体来说，我们将进行一项 对N=135名参与者(年龄在13-21岁)进行加速纵向fMRI研究，合并临床分析 酒精使用严重程度，跨多个任务的新颖性驱动的探索的计算建模，基于模型 在三个纵向时间点分解fMRI数据，并基于智能手机进行日常日记评估，以 在实验室外探索与酒精和新奇事物相关的体内决策。在目标1中，我们将测试 假设新颖性驱动的探索的规范成熟--即战略、目标的扩展-- 定向探索以优化选择-将受到酒精使用严重程度增加的负面影响。 此外，我们将使用基于纵向模型的功能磁共振成像来确定定向探索的这种扩展 是由于与年龄相关的神经编码增加了探索新选择的潜在价值 额顶叶(即额叶顶叶皮质、背外侧前额叶皮质和顶内小叶)和动机 (即纹状体、杏仁核和眶前叶皮质)神经回路。在目标2中，我们将对比新颖性驱动 探索最大化收益而不是最小化损失，假设潜在的存在 惩罚应该减少探索性行为，因为个人有动机避免潜在的损失。 奖励和惩罚诱发的神经反应之间的区别在青少年中变得迟钝 酒精使用问题，因此我们假设新颖性探索的差异门跨越收益 与酒精使用严重程度较高的青少年相比，酒精使用严重程度较高的青少年的情况会减少。最后，在目标3中，我们将 使用通过智能手机发送的日常日记提示来确定我们实验室的生态相关性- 基于决策分析的预测现实世界酒精和新奇行为的方法。这 计算表型、神经成像和生态环境评估的三角测量还没有 在现有研究中进行，并可以确定要考虑的新的新颖性驱动的探索维度 在成瘾神经临床评估框架的未来迭代中。与卡茨的早期阶段一致 研究人员机制--这种计算发展科学方法将代表一种创新的 这将使PI进入一个新的研究方向：利用他在青少年方面的技能和专业知识 神经成像侧重于决策神经回路的发展和酒精使用问题的风险 在青春期。

PROJECT SUMMARY Exploring novel and unfamiliar foods, friend groups, and activities during adolescence critically shapes our preferences and personalities in adulthood. Conversely, for adolescents who engage in underage drinking, such novelty-seeking can be maladaptive and lead to the development of chronic alcohol use problems. Cross- sectional studies suggest that individuals become more strategic in their use of goal-directed exploration to optimize choice during the transition from adolescence to young adulthood. The core hypothesis of the proposed study is that the maturation of directed exploration is blunted or lagged in adolescents who experiment with alcohol and go on to develop increased alcohol use problems. Specifically, we will conduct an accelerated longitudinal fMRI study of N=135 participants (recruited at 13-21 years), merging clinical assays of alcohol use severity, computational modeling of novelty-driven exploration across multiple tasks, model-based decomposition of fMRI data at three longitudinal timepoints, and smartphone-based daily diary assessments to probe alcohol- and novelty-related decision making in vivo outside of the laboratory. In Aim 1 we will test the hypothesis that the normative maturation of novelty-driven exploration—i.e., expansion of strategic, goal- directed exploration to optimize choice—will be negatively modulated by increased alcohol use severity. Further, we will use longitudinal model-based fMRI to determine whether this expansion of directed exploration is driven by age-related increases in neural encoding of the latent value of exploring new options in frontoparietal (i.e., frontopolar cortex, dorsolateral prefrontal cortex, and intraparietal lobule) and motivational (i.e., striatum, amygdala, and orbitofrontal cortex) neural circuits. In Aim 2 we will contrast novelty-driven exploration to maximize gains versus minimize losses, hypothesizing that the presence of potential punishments should decrease exploratory behavior as individuals are motivated to avoid potential losses. Differentiation between reward- and punishment-evoked neural responses is blunted in adolescents with alcohol use problems, therefore we hypothesize that differential gating of novelty exploration across gain versus loss contexts will be diminished in adolescents with higher alcohol use severity. Lastly, in Aim 3 we will use daily diary prompts delivered via smartphone to determine the ecological relevance of our laboratory- based decision making assays for predicting real-world alcohol- and novelty-directed behaviors. This triangulation of computational phenotyping, neuroimaging, and ecologically-situated assessments has not been performed in existing studies, and could identify a new novelty-driven exploration dimension to be considered in future iterations of the Addictions Neuroclinical Assessment framework. In line with the Katz Early Stage Investigator mechanism—this computational developmental science approach will represent an innovative advance that will launch the PI in a new research direction: leveraging his skills and expertise in adolescent neuroimaging to focus on the development of decision making neurocircuitry and risk for alcohol use problems in adolescence.