Mechanism of Impulsive Choice

具体目标1：量化和描述MA依赖者与对照组在决策过程中对延迟、概率和奖赏大小的大脑反应的参数变化。 具体目标2：使用功能相关性、扩散张量成像(DTI)和基于体素的形态计量学(VBM)，量化大脑连接中断作为MA冲动增加的一个因素。 具体目标3：在人类和啮齿类动物中，研究网络连接的神经免疫中断有助于甲基苯丙胺依赖的冲动选择的假设 方法：从当地居民治疗项目和广告中招募45名积极使用甲基苯丙胺(MA)依赖者、45名MA依赖者缓解早期(1~6个月)患者和45名对照。受试者将接受功能磁共振成像(FMRI)、扩散张量成像(DTI)和基于体素的形态测量(VBM)的评估，以确定支持冲动选择的解剖和功能网络。 组件9将从两个品系中选择饮用高和低MA的小鼠(组件9)，分别给小鼠长期服用MA，然后长期给药，然后禁欲和生理盐水载体(总共120只小鼠)，然后训练它们执行动物版本的延迟折扣任务。组件9将向该组件提供这些小鼠的大脑，以进行体外MRI扫描。我们将在老鼠和人脑中进行平行分析。 免疫失调和差异基因表达的测量(从组成部分8开始)将作为人类和执行冲动任务的动物决策网络中断的因素进行调查。

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.