fMRI Study of Nicotine Exposure in Discordant Sib-Pairs

这个项目的总体目标是了解尼古丁依赖的功能神经解剖学基础 通过检查慢性和急性尼古丁暴露适应的神经基质， 容易对尼古丁产生依赖我们提出了一个内表型研究的同胞对不一致， 与代表一生烟草使用不同程度的吸烟表型一致。目标对将 包括：30名目前吸烟者/曾经吸烟者、30名新吸烟者/曾经吸烟者和30名曾经吸烟者/曾经吸烟者（曾经 吸烟者指接触香烟，但没有进展到经常吸烟）。这允许对 遗传/环境脆弱性（见于先证者和兄弟姐妹中的先证者吸烟状况） 尼古丁暴露（仅见于吸烟状态的先证者）。评估将包括重复测量功能磁共振成像 有和没有尼古丁激发的方案，以允许根据急性尼古丁检查脑功能 暴露以及遗传/环境脆弱性和慢性尼古丁暴露。 我们将评估不同的区域脑tMRI脑氧水平依赖（BOLD）信号激活， 四个任务的反应，包括两个认知挑战敲击行为抑制（停止信号任务）和 言语工作记忆（2-Back任务），一种线索激发范式，旨在引起一种渴望状态， 情绪处理任务感兴趣的特定区域（ROI）包括：杏仁核、丘脑核、尾状核、杏仁核、尾状核、杏仁核。 前额叶皮层的特定区域。我们预计：1）大脑对吸烟和情绪线索的反应 与尼古丁摄入量相比，尼古丁戒断期间的吸烟率会更高，特别是在当前吸烟者中。（二） 尼古丁摄入后，ROI的激活将增加，行为表现将改善， 吸烟史3)当前吸烟者将表现出显著的性能下降和 尼古丁戒断期间ROI的激活。4)目前吸烟者的同胞将表现出更差的注意力处理 尼古丁戒断过程中行为抑制较少，提示诱发的渴求和ROls激活较多 比以前和曾经吸烟的兄弟姐妹更好。我们预期在曾经吸烟的人中，对吸烟提示的反应没有相对激活 同胞对结果应导致发展一个全面的模型的功能神经解剖学基础 在尼古丁依赖中，t_om过程从维持尼古丁依赖循环到介导尼古丁依赖循环的过程， 对尼古丁依赖的脆弱性。

The overall goal of this project is to understand the functional neuroanatomical bases of nicotine dependence through examination of the neural substrates underlying adaptations to chronic and acute nicotine exposure as well as vulnerability to nicotine dependence. We propose an endophenotypic study of sib-pairs discordant and concordant for smoking phenotypes that represent differing degrees of lifetime tobacco use. Targeted pairs will include: 30 current smoker/ever smokers, 30 tbnner smoker/ever smokers, and 30 ever smoker/ever smoker (ever smoker denotes exposure to cigarettes but no progression to regular smoking). This allows partitioning of genetic/environmental vulnerability (seen in probands and siblings by smoking status of the proband) from chronic nicotine exposure (seen only in probands by smoking status). Assessment wilt include a repeated measures fMRI protocol with and without nicotine challenge to permit examination of brain function according to acute nicotine exposure as well as genetic/environmental vulnerability and chronic nicotine exposure. We will assess differences in regional brain tMRI brain oxygen level dependent (BOLD) signal activation in response to four tasks including two cognitive challenges tapping behavioral inhibition (stop signal task) and verbal working memory (2-Back task), a cue-provocation paradigm, designed to elicit a state of craving, and an emotion processing task. Specific regions of interest (ROI) include: the amygdala, nucleus accumbens, caudate nucleus, and specific areas of the prefrontal cortex. We expect: 1) Brain response to smoking and emotional cues will be greater during nicotine abstinence compared to nicotine intake, particularly among current smokers. 2) Activation of ROIs will increase and behavioral performance will improve following nicotine intake regardless of smoking history. 3)Current smokers will exhibit significant decrements in performance and reductions in activation of ROIs during nicotine abstinence. 4) Sibs of current smokers wilt exhibit worse attentional processing and less behavioral inhibition in during nicotine abstinence and greater cue-elicited craving and activation of ROls than sibs of former and ever smokers. We expect no relative activation in response to smoking cues in ever smoker sib pairs. Results should lead to the development of a comprehensive model of the functional neuroanatomic basis of nicotine dependence, t_om processes maintaining the nicotine dependence cycle to those mediating vulnerability to nicotine dependence.