Reward context and brain signatures of drug abuse risk in adolescents

青少年因危险行为而臭名昭著，例如开始吸毒和酗酒。一种流行的理论认为 青少年的冒险行为部分归因于发育较早的中脑边缘的强健功能 动机神经回路不受不成熟的额叶皮质执行控制神经回路的控制。 中脑边缘招募(包括腹侧)增加的功能磁共振成像(FMRI)表现 纹状体(VS)与成人相比，青少年的奖励支持了这一理论，因为VS被激活 反映了对激励措施的隐蔽情绪反应。然而，其他研究表明，迟钝的招聘与招聘 与成年人相比，青少年的奖赏预测线索。任务功能可能会解释这种差异，但 在年龄段的比较中，从来没有系统地在受试者内部进行探索。例如，以下任务 在青少年中被激发的相对增加的VS激活具有多彩的意象，不确定的回报 大小，做出选择，以及暗示--应变学习。相反，研究表明，与 青少年在警觉密集型运动任务中的奖赏前景激活 性能。青少年动机神经回路可能特别被情感成分激活 而完全发育的成人大脑可能会更有力地招募V作为完全发育的一部分 执行控制反馈循环(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，成年人也会通过警惕来招募VS。在乐器演奏过程中 青少年的行为VS招募可能主要是由奖励的情感成分驱动的， 而成人的VS招募可能主要反映了最佳的注意分配。这个R21项目将启动 旨在为人类奖赏的发展提供关键的背景细微差别的研究计划 正在处理。神经典型的青少年和成年人将执行一项新的fMRI奖励任务，该任务保持不变 所有奖励的期望值，但奖励是否为1)：显性的，2)取决于警觉密集的，则各不相同 响应，以及3)取决于成功的选择而不是单一的响应选项。最后，动态因果关系 建模将被用来测量作为年龄和奖励需求的函数的皮质纹状体连接性。如果 青少年通过选择奖励或不确定的回报的反应来表现出更大的激活度，而成年人 在要求执行控制权的审判中表现出更大的奖励反应，这将有助于解决有争议的问题 文献，并阐明最能激发青少年动机回路的奖励背景。发现 最能吸引青少年动机神经回路的激励环境可以告诉每个人：a) 预防青少年危险行为的政策，b)应急管理和其他以激励为基础的疗法 青春期的行为变化，以及c)纵向发展项目的组成部分，通过确定 奖励任务的特点是产生最强健的中脑边缘信号，并且与药物滥用风险最密切。

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.