Interoceptive Dysregulation in Adolescents At Risk for Substance Dependence

项目1：青少年使用苯丙胺药物是一个主要的公共卫生问题，11%的高中学生 老年人使用过甲基苯丙胺或非处方服用的药用苯丙胺 目的(MTF，2008)。内感是指通过传入C纤维感知和处理身体内部状态， 它整合在岛叶皮质中。先前的研究表明，岛叶皮质功能与 到上瘾的各个方面。然而，内感系统和岛叶皮质在大脑中的确切作用 物质依赖的发展尚不清楚。在这里，我们假设岛叶皮质反应迟钝。 对有物质风险的青少年的内感刺激，但对药物线索的高反应 基于青年时期反复实验的依赖。在本项目中，我们将比较 内感系统对正负效价的内感和药物线索刺激的反应 之间：(1)目前使用安非他明的高危青少年，(2)适应力强的青少年 安非他明的前使用者，但在没有达到依赖标准的情况下停止使用，以及(3)控制 没有安非他明使用史的青少年。目标是：(1)确定半岛在以下方面的作用 苯丙胺依赖高危青少年的内感信息处理，出现 对苯丙胺依赖的恢复力，以及健康对照青少年；(2)确定 在有苯丙胺依赖风险的青少年中处理与线索相关的信息时， 对苯丙胺依赖有弹性，并与健康对照青少年；(3)修改神经成像 响应项目3(动物研究)的范例，以更好地表征内感回路在脑损伤中的作用 苯丙胺高危青少年的直接正面(高)与负性(戒断/宿醉)效应 (4)通过比较来考察青春期内感觉系统的发展。 青少年对照和成人对照(来自项目2)关于内感和药物线索的激活模式 任务。综上所述，这些研究将有助于确定内感失调是如何在 青少年有使用安非他明的危险。这些见解将被用于未来的研究，旨在改变 岛叶皮质的反应性，作为预防或治疗物质依赖的一种方式。合并结果 项目1和项目2将对岛叶皮质和枕叶间皮层的作用产生重要的见解 在安非他明依赖的风险中发挥作用。最后，这项研究的结果将为我们做好准备 用于对该中心P50扩展的内感功能障碍的纵向研究。

Project 1: Adolescents' use of amphetamine drugs is a major public health concern, as 11% of high school seniors have used methamphetamine or a pharmaceufical amphetamine taken other than for prescribed purposes (MTF, 2008). Interoception refers to sensing and processing the internal body state via afferent Cfibers, which is integrated in the insular cortex. Previous invesfigafions have linked insular cortex functioning to aspects of addiction. However, the precise role of the interoceptive system and insular cortex in the development of substance dependence is unclear. Here, we hypothesize that the insular cortex is hyporesponsive to interoceptive stimulation, but hyper-reactive to drug cues in adolescents at risk for substance dependence based on repeated experimentation during youth. In this project, we will compare activity of the interoceptive system in response to positively and negatively valenced interoceptive and drug cue stimuli between: (1) at-risk adolescents who are current users of amphetamines, (2) resilient adolescents who are former users of amphetamines but stopped without ever meeting dependence criteria, and (3) control adolescents with no history of amphetamines use. The aims are: (1) to determine the role of the insula in processing interoceptive information in teens at risk for amphetamine dependence, teens who appear resilient to amphetamine dependence, and healthy control adolescents; (2) to determine the role of the insula in processing cue-related informafion in teens at risk for amphetamine dependence, teens who have been resilient to amphetamine dependence, and healthy control adolescents; (3) to modify neuroimaging paradigms in response to Project 3 (animal studies) to better characterize the role of interoceptive circuitry in the direct posifive (high) versus negafive (withdrawal/hangover) effects among teens at risk for amphetamine dependence; and (4) examine the development of the interoceptive system in adolescence by comparing adolescent controls and adult controls (from Project 2) on activation patterns to interoceptive and drug cue tasks. Together, these studies will help determine how interoceptive dysregulation plays a role in putting adolescents at risk for amphetamine use. These insights will be used in future studies aimed at altering the reactivity of the insular cortex as a way of preventing or treating substance dependence. Combining results from Projects 1 and 2 will yield important insights into the role of the insular cortex and interocepfive functioning in risk for amphetamine dependence in general. Finally, the outcome of this study will prepare us for longitudinal studies of interoceptive dysfunction in a P50 extension of this Center.