Now versus Later decision Making: Effects of frontal development and alcohol use

描述（由申请人提供）：个体在青春期晚期发生酒精使用障碍（AUD）的风险最大（Kandel and Logan, 1984; Brown et al., 2008），可能是由于青春期晚期/青年的相对冲动。Kandel和Logan（1984）认为，通常发生在25岁左右的大量饮酒的减少可能反映了一个成熟或发展的过程，因为涉及自我调节和冲动控制的额叶结构的发展在20岁左右完成（Giedd, 2004； Hooper等人，2004；Rubia等人，2006；Eshel等人，2007）。虽然人们普遍接受额叶回路在青少年后期仍在成熟的观点，但迄今为止还没有研究专门研究在现在和以后的决策过程中额叶回路功能的变化，这是一种可量化的冲动衡量标准。拟议的研究将比较晚期青少年（18-23岁）和成年人（25-40岁），使用功能性磁共振成像方法来识别在现在和以后决策过程中参与的大脑区域的差异。此外，我们将确定大量饮酒是否与这些神经回路中正常观察到的年龄相关差异异常有关。我们的中心假设是，额叶回路的不成熟和纹状体-边缘结构信号的相对增加促进了青少年晚期的冲动决策。我们将通过以下具体目标来验证我们的中心假设：1)识别与青少年晚期和成年人的现在/以后决策相关的额纹状体回路的功能差异。2)确定重度饮酒成人的冲动性决策是否与额叶回路功能不成熟的迹象有关。为了实现本研究计划的目标，将使用先前验证的延迟折扣任务（Mitchell et al., 2005; Boettiger et al., 2007）在功能MRI的背景下测量晚期青少年和成人的Now/Later决策行为。我们将试图确定大脑结构功能的年龄依赖性差异是否与决策的年龄依赖性差异相关。这些研究将在中度和重度饮酒人群中进行，以确定酒精使用如何影响参与现在/以后决策的大脑结构的年龄相关变化。这项研究将显著提高我们对从青春期晚期到成年期决策变化的神经基础的理解，这可能会解释为什么青春期晚期患酒精使用障碍的风险增加。对产生酒精使用障碍的潜在风险机制的更多了解，可能有助于开发更好的治疗或干预措施。

DESCRIPTION (provided by applicant): Individuals are at greatest risk for developing an alcohol use disorder (AUD) during late adolescence (Kandel and Logan, 1984; Brown et al., 2008), possibly due to the relative impulsiveness of late adolescents/young adults. Kandel and Logan (1984) have suggested that the decline in heavy alcohol use that typically occurs in the mid-twenties may reflect a maturational or developmental process, as the development of frontal structures implicated in self-regulation and impulse control is complete in humans around the early- to-mid twenties (Giedd, 2004; Hooper et al., 2004; Rubia et al., 2006; Eshel et al., 2007). Although there is general acceptance of the idea that frontal circuits are still maturing in late adolescents no work to date has specifically investigated changes in the function of frontal circuits engaged during Now versus Later decision making, a quantifiable measure of impulsiveness. The proposed studies will compare late adolescents (ages 18-23) and adults (ages 25-40) using functional MRI approaches to identify differences in the brain areas engaged during Now versus Later decision-making. In addition, we will determine whether heavy alcohol use is associated with abnormalities in normally observed age-related differences in these neural circuits. Our central hypothesis is that immaturity in frontal circuits and relatively increased signaling in striato-limbic structures promote impulsive decision making in late adolescents. We will test our central hypothesis via the following Specific Aims: 1) Indentify functional differences in frontostriatal circuits associated with Now/Later decision making in late adolescents versus adults. 2) Determine whether the impulsive decision-making observed in heavy drinking adults is associated with signs of functional immaturity in frontal circuits. To achieve the goals of this research plan, a previously validated delay-discounting task (Mitchell et al., 2005; Boettiger et al., 2007) will be used to measure Now/Later decision making behavior in late adolescents and adults in the context of functional MRI. We will seek to determine whether age-dependent differences in the function of brain structures of interest correlate with age-dependent differences in decision-making. These studies will be conducted in both moderate and heavy drinking populations to determine how alcohol use impacts age- related changes in brain structures engaged in Now/Later decision making. This research stands to significantly improve our understanding of the neural underpinnings of changes in decision-making from late adolescence to adulthood, which may bear on why late adolescents are at an increased risk for developing alcohol use disorders. Greater knowledge of the mechanisms underlying risk for developing alcohol use disorders may allow for the development of better treatments or interventions. PUBLIC HEALTH RELEVANCE: This research project seeks to understand the neurobiological bases for the decline in the tendency to choose smaller, sooner rewards ("Now") over larger, later rewards ("Later") from late adolescence to early adulthood, a tendency that also characterizes individuals with alcohol use disorders. Studying developmental changes in the function of frontal structures that regulate Now/Later decision-making may provide insight into why late adolescents are at increased risk for developing alcohol use disorders, which may in turn aid in the development of new prevention and treatment approaches for this vulnerable age group.