Reward context and brain signatures of drug abuse risk in adolescents

青少年因危险行为而臭名昭著，如吸毒和酗酒。一种流行的理论认为 青少年的冒险行为部分归因于早期发育的中脑边缘系统的强大功能， 不成熟的额叶皮层执行控制神经回路控制不良的动机神经回路。 功能性磁共振成像（fMRI）结果显示，中脑边缘募集（包括腹侧）增加， 纹状体（VS））在青少年与成年人相比，奖励支持这一理论，在激活VS 反映了对激励的隐性情绪反应。然而，其他研究表明， 与成年人相比，青少年的奖励预测线索。任务特征可以解释这种差异， 从未在年龄组比较中进行过系统的受试者内研究。例如， 在青少年中引起的相对增加的VS激活具有丰富多彩的图像，不确定的收益， 重要性、选择和线索-偶然性学习。相反，研究表明， 青少年在警戒密集型运动任务中的奖励前景激活 性能青少年的动机神经回路可能特别被情感成分激活 而完全发育的成年人大脑可能会更有力地招募VS作为完全发育的大脑的一部分。 执行控制反馈回路（包括VS以纳入激励信息）以维持注意力。 值得注意的是，即使在没有激励的情况下，成年人的警惕性也会招募VS。在仪器期间 行为，青少年的VS招募可能主要由奖励的情感成分驱动， 而成年人的VS募集可能主要反映了最佳的注意力分配。R21项目将启动 一项旨在为人类奖励的发展提供关键的背景细微差别的研究计划 处理.神经正常的青少年和成年人将执行一种新的fMRI奖励任务， 所有奖励的期望值，但不同的奖励是1）：明确的，2）依赖于警戒密集型 3）依赖于成功的选择，而不是单一的响应选项。最后，动态因果 将采用建模来测量作为年龄和奖赏需求的函数的皮质纹状体连接。如果 青少年通过选择奖励或不确定回报的反应表现出更大的VS激活，成年人 在要求执行控制的试验中显示出更大的VS奖励反应，这将有助于解决有争议的 文献，并澄清奖励的情况下，最好的青少年参与激励电路。发现所述 最强烈地参与青少年动机神经回路的激励环境可以告知以下每一个：a） 预防青少年危险行为的政策，B）应急管理和其他基于激励的疗法， 行为变化在青春期，和c）组成部分的纵向发展项目，通过确定 奖励任务的特点，产生最强大的中脑边缘信号，是最密切的药物滥用风险。

Adolescents are notorious for risky behavior, such as drug and alcohol use initiation. A popular theory posits that adolescent risk-taking is partly attributable to robust functioning of earlier-developing mesolimbic motivational neurocircuitry that is poorly controlled by immature frontocortical executive-control neurocircuitry. Functional magnetic resonance imaging (fMRI) findings of increased mesolimbic recruitment (including ventral striatum (VS)) by rewards in adolescents compared to adults support this theory, in that activation of VS reflects covert emotional responses to incentives. Other studies, however, have shown blunted VS recruitment by reward-predictive cues in adolescents compared to adults. Task features may explain this discrepancy, but have never been systematically explored within-subject in age-group comparison. For example, tasks that elicited relatively increased VS activation in adolescents have featured colorful imagery, payoffs of uncertain magnitude, making choices, and cue-contingency learning. Conversely, studies have shown reduced VS activation by reward prospects in adolescents in tasks with explicit payoffs for vigilance-intensive motor performance. Adolescent motivational neurocircuitry may be especially activated by the affective components of rewards, whereas the fully-developed adult brain may more robustly recruit VS as part of a fully-developed executive-control feedback loop (that includes VS to incorporate incentive information) to sustain attention. Notably, the VS is also recruited by vigilance in adults even in non-incentivized contexts. During instrumental behavior, VS recruitment in adolescents may be primarily driven by the affective components of reward, whereas VS recruitment in adults may primarily reflect optimal attention allocation. This R21 project will launch a research program aimed at providing critical contextual nuance to the development of human reward processing. Neurotypical adolescents and adults will perform a novel fMRI reward task that holds constant the expected value of all rewards, but varies whether rewards are 1): explicit, 2) dependent on vigilance-intensive responding, and 3) dependent on a successful choice versus a single response option. Finally, dynamic causal modeling will be employed to measure corticostriatal connectivity as a function of age and reward demands. If adolescents show greater VS activation by choosing responses for rewards or for uncertain payoffs, and adults show greater VS responses to reward in executive control-demanding trials, it will help resolve controversial literature, and clarify reward contexts that best engage motivational circuitry in adolescents. Discovering the incentive contexts that most strongly engage adolescent motivational neurocircuitry can inform each of: a) policies to prevent risky behavior in teens, b) contingency management and other incentive-based therapies for behavior change in adolescence, and c) components of longitudinal developmental projects, by identifying reward task features that yield the most robust mesolimbic signal, and are most germane to drug abuse risk.