fMRI Study of Nicotine Exposure in Discordant Sib-Pairs

该项目的总体目标是通过检查慢性和急性尼古丁暴露的适应性以及尼古丁依赖的脆弱性的神经基质，了解尼古丁依赖的功能神经解剖学基础。我们提出了一个内表型研究的同胞对不一致和一致的吸烟表型，代表不同程度的终身烟草使用。目标对将包括：30名当前吸烟者/曾经吸烟者、30名既往吸烟者/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）。这使得遗传/环境的脆弱性（见于先证者和兄弟姐妹的吸烟状态）从慢性尼古丁暴露（仅见于先证者的吸烟状态）。评估将包括重复测量fMRI方案（有和无尼古丁激发），以根据急性尼古丁暴露以及遗传/环境脆弱性和慢性尼古丁暴露检查脑功能。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，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-回任务），线索激发范式，旨在引起渴望的状态，和情绪处理任务。感兴趣的特定区域（ROI）包括：杏仁核、脑桥核、尾状核和前额皮质的特定区域。我们期望：1）与尼古丁摄入量相比，尼古丁戒断期间大脑对吸烟和情绪线索的反应更大，特别是在当前吸烟者中。（二） 无论吸烟史如何，尼古丁摄入后ROI的激活都会增加，行为表现也会改善。3)当前吸烟者在尼古丁戒断期间表现出显著的性能下降和ROI激活减少。4)当前吸烟者的同胞在尼古丁戒断期间将表现出更差的注意力处理和更少的行为抑制，并且比先前和曾经吸烟者的同胞表现出更大的线索引起的渴望和ROls的激活。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 同胞对结果应导致尼古丁依赖的功能性神经解剖学基础的综合模型的发展，从维持尼古丁依赖周期的过程到那些介导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 cute 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 former 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 will 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 will 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, from processes maintaining the nicotine dependence cycle to those mediating vulnerability to nicotine dependence.