Neurodevelopment of exploration and alcohol problems in adolescence

项目摘要 在青春期探索新奇和不熟悉的食物、朋友群体和活动， 成年后的偏好和个性。相反，对于未成年饮酒的青少年， 这种寻求新奇的行为可能是不适应的，并导致慢性酒精使用问题的发展。交叉- 分段研究表明，个体在使用目标导向探索时变得更具战略性， 在从青春期到青年期的过渡期间优化选择。的核心假设 一项研究表明，在青少年中，定向探索的成熟是迟钝或滞后的， 尝试酒精并继续发展酒精使用问题。具体来说，我们将进行一项 对N=135名参与者（招募年龄为13-21岁）进行的加速纵向fMRI研究， 酒精使用的严重程度，跨多个任务的新颖性驱动的探索的计算建模，基于模型的 在三个纵向时间点对fMRI数据进行分解，以及基于智能手机的每日日记评估， 在实验室外的体内探索酒精和新奇相关的决策。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，战略扩张，目标- 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，我们将使用纵向模型为基础的功能磁共振成像，以确定是否这种扩展的定向探索 是由年龄相关的神经编码的增加驱动的，神经编码的潜在价值是探索新的选择， 额顶骨（即，额极皮层、背外侧前额叶皮层和顶内小叶）和动机性 (i.e.,纹状体、杏仁核和眶额皮质）神经回路。在目标2中，我们将对比创新驱动 探索，以最大限度地提高收益与减少损失，假设存在的潜力， 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是迟钝的， 酒精使用问题，因此，我们假设，差异门控的新奇探索跨越增益 在酒精使用严重程度较高的青少年中，与损失背景的对比将减少。最后，在目标3中， 使用通过智能手机提供的每日日记提示，以确定我们实验室的生态相关性- 基于决策分析，用于预测现实世界中的酒精和新奇行为。这 计算表型、神经影像学和生态学评估的三角测量尚未被 在现有的研究中进行，并可以确定一个新的新颖性驱动的探索方面加以考虑 在成瘾神经临床评估框架的未来迭代中。与Katz早期阶段一致 研究者机制-这种计算发展科学的方法将代表一种创新的 这将在一个新的研究方向推出PI：利用他的技能和专业知识在青少年 神经影像学，专注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.