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

描述(由申请人提供)：个人在青春期后期患酒精使用障碍(AUD)的风险最大(Kandel和Logan，1984；Brown等人，2008)，可能是由于青少年后期/年轻人的相对冲动。Kandel和Logan(1984)提出，重度酒精使用的减少通常发生在25岁左右，这可能反映了一个成熟或发育的过程，因为涉及自我调节和冲动控制的额叶结构的发展在25岁左右的人类中已经完成(Giedd，2004；Hooper等人，2004；Rubia等人，2006；Eshel等人，2007)。尽管人们普遍接受这一观点，即青少年后期的额叶回路仍处于成熟阶段，但到目前为止，还没有工作专门研究在现在与以后的决策过程中参与的额叶回路功能的变化，这是一种可量化的冲动衡量标准。这项拟议的研究将使用功能磁共振方法对晚期青少年(18-23岁)和成年人(25-40岁)进行比较，以确定现在参与决策的大脑区域与后来做出决策的大脑区域的差异。此外，我们将确定大量饮酒是否与正常观察到的这些神经回路中与年龄相关的差异的异常有关。我们的中心假设是，额叶回路的不成熟和纹状体-边缘结构中信号的相对增加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)确定与青少年晚期和成人现在/以后的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。为了实现这项研究计划的目标，将使用先前验证的延迟折扣任务(Mitchell等人，2005；BoetTiger等人，2007)在功能磁共振的背景下测量青少年和成年人现在/将来的决策行为。我们将寻求确定感兴趣的大脑结构功能的年龄差异是否与年龄相关的决策差异相关。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青春期后期到成年期决策变化的神经基础的理解，这可能与为什么晚期青少年患酒精使用障碍的风险增加有关。对酒精使用障碍潜在风险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.