Mechanism of Impulsive Choice

具体目标1：量化和表征MA依赖个体与对照组在决策过程中对延迟、概率和奖励幅度的脑反应的参数变化。 具体目标二：使用功能相关性、弥散张量成像（DTI）和基于体素的形态测量（VBM）量化大脑连接中断作为MA冲动性增加的潜在因素。 具体目标3：在人类和啮齿类动物中调查神经免疫网络连接中断有助于甲基苯丙胺依赖的冲动选择的假设 方法：将从当地住院治疗计划和广告中招募45名积极使用甲基苯丙胺（MA）的依赖者、45名早期（1至6个月）缓解的MA依赖者和45名对照者。受试者将接受功能性磁共振成像（fMRI）、扩散张量成像（DTI）和基于体素的形态测定（VBM）评估，以确定冲动选择背后的解剖和功能网络。 组分9将使来自选择用于高和低MA饮用的两个品系（组分9）的小鼠暴露于长期MA施用、长期施用然后禁欲和盐水媒介物（总共120只小鼠），然后训练它们执行延迟折扣任务的动物版本。组件9将向该组件提供这些小鼠的大脑，以进行离体MRI扫描。我们将在小鼠和人脑中进行平行分析。 将研究免疫失调和差异基因表达（来自组件8）的措施，作为人类和执行冲动任务的动物决策网络中断的因素。

Specific Aim 1: Quantify and characterize the parametric variation of cerebral response to delay, probability, and reward magnitude during decision making in MA dependent individuals vs Controls. Specific Aim 2: Quantify disruptions in cerebral connectivity as a factor underlying increased impulsivity in MA using functional correlation, diffusion-tensor imaging (DTI) and voxel based morphometry (VBM). Specific Aim 3: Investigate, in humans and rodents, the hypothesis that neuroimmune disruption of network connectivity contributes to impulsive choice in methamphetamine dependence METHODS: Forty-five actively using methamphetamine (MA) dependent individuals, 45 MA dependent patients in early (1 to 6 months) remission and 45 controls will be recruited from local residential treatment programs and by advertisement. Subjects will be evaluated with functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI) and voxel based morphometry (VBM) in order to identify the anatomical and functional networks that underlie impulsive choice. Component 9 will expose mice from two lines selected for high and low MA drinking (Component 9), to chronic MA administration, chronic administration followed by abstinence and saline vehicle (total of 120 mice) and then train them to perform an animal version of the delay discounting task. Component 9 will provide brains of these mice to this component for ex-vivo MRI scanning. We will perform parallel analyses in mouse and human brains. Measures of immune dysregulation and differential gene expression (from Component 8) will be investigated as factors responsible for disruption of decision networks in humans and in animals performing impulsivity tasks.