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

描述（由申请人提供）：个体在青春期后期发展酒精使用障碍（AUD）的风险最大（Kandel和Logan，1984; Brown等人，2008年），可能是由于后期青少年/年轻人的相对冲动。Kandel和Logan（1984）认为，通常发生在20多岁的重度酒精使用的下降可能反映了一个成熟或发育过程，因为涉及自我调节和冲动控制的额叶结构的发育在20多岁的早期到中期完成（Giedd，2004; Hooper等人，2004; Rubia等人，2006; Eshel等人，2007年）。虽然人们普遍接受这样的观点，即青少年后期的额叶回路仍在成熟，但迄今为止还没有任何工作专门研究过在现在与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性测量方法。拟议的研究将使用功能性MRI方法比较晚期青少年（18-23岁）和成年人（25-40岁），以确定现在与以后决策过程中大脑区域的差异。此外，我们将确定重度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中相对增加的信号传导促进了青少年后期的冲动决策。我们将通过以下具体目标来检验我们的中心假设：1）识别青少年晚期与成人中与现在/以后决策相关的额纹状体回路的功能差异。2)确定在大量饮酒的成年人中观察到的冲动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，先前验证的延迟折扣任务（Mitchell等人，2005; Boettiger等人，2007）将被用来衡量现在/以后的决策行为，在功能性MRI的背景下，在青少年和成年人。我们将试图确定是否年龄依赖性差异的功能的大脑结构的利益与年龄依赖性差异的决策。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中与年龄相关的变化。 这项研究将显著提高我们对从青春期后期到成年决策变化的神经基础的理解，这可能会影响为什么青少年后期患酒精使用障碍的风险增加。更多地了解发展酒精使用障碍的潜在风险机制可能有助于开发更好的治疗或干预措施。 公共卫生相关性：该研究项目旨在了解从青春期后期到成年早期，选择较小，较早的奖励（“现在”）而不是较大，较晚的奖励（“后来”）的倾向下降的神经生物学基础，这种倾向也是酒精使用障碍患者的特征。研究调节现在/以后决策的额叶结构功能的发育变化可能会深入了解为什么晚期青少年患酒精使用障碍的风险增加，这反过来可能有助于为这个弱势群体开发新的预防和治疗方法。年龄组。

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.