NICOTINE WITHDRAWAL, SMOKING & COGNITION: AN FMRI STUDY

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 每年因尼古丁依赖而死亡的人数超过所有非法药物滥用死亡人数的总和。这种障碍的原因和机制包括社会，生理和认知因素。虽然对认知的影响是吸烟的主要原因是值得怀疑的，但人们为什么吸烟的自我报告表明，这些影响是重要的贡献者。这项工作的主要目标是阐明吸烟和戒断的认知影响所涉及的神经回路。我们将测试调节认知控制的前额叶大脑区域的活动在尼古丁戒断和饱腹感中的差异。认知控制指的是引导自愿的复杂行动的大脑功能。我们还将测试吸烟者和非吸烟者与认知表现相关的大脑活动模式有何不同。我们的长期目标是提供有关尼古丁和吸烟如何影响对认知功能至关重要的脑回路的信息，以及这些功能在吸烟者和非吸烟者中的差异（无论是吸烟的影响还是尼古丁依赖的病因因素）。先前和正在进行的研究表明，戒烟，尼古丁管理，甚至吸烟史都会影响认知控制测试的表现。对这些任务的大脑成像研究显示，背外侧前额叶皮层（DLPFC）和前扣带皮层（ACC）以及其他大脑区域都被激活。一个这样的任务是Stroop颜色词干扰任务，它需要集中注意力和反应抑制，而冲突的刺激。另一个显示吸烟可能影响的认知控制测试是N-Back任务，它需要工作记忆，通常会激活DLPFC。我们将使用功能性磁共振成像（fMRI）来测量在执行这两项研究任务时的大脑激活。我们对大脑区域激活的测量将是磁共振信号的变化，代表相对的血液动力学变化。我们有两个主要目标。我们的第一个具体目标是确定吸烟史和戒烟对N-Back任务和Stroop任务执行过程中大脑功能的影响。吸烟者和非吸烟者将接受功能磁共振成像和认知激活测试。吸烟者将在饱腹状态（随意吸烟后）以及戒烟15-17小时后接受检测。我们的第二个目标是确定吸烟是否会逆转大脑激活的差异和/或改善N-Back和Stroop任务的表现。在每次初始认知激活测试后，在饱腹感（随意吸烟后）和戒烟期间，允许吸烟者吸烟（随意吸烟10分钟）并重新测试。不吸烟者作为对照，将在相应时间重新测试。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. More deaths each year are attributable to nicotine dependence than to all illicit drug abuse combined. The causes and mechanisms of this disorder include social, physiological and cognitive components. While it is doubtful that effects on cognition are the primary reason for cigarette smoking, self-reports of why people smoke indicate that these effects are significant contributors. The broad objective of this work is to elucidate the neural circuitry involved in the cognitive effects of smoking and withdrawal. We will test how the activity of prefrontal brain regions that mediate cognitive control differs in nicotine abstinence and satiety. Cognitive control refers to brain functions that guide voluntary, complex actions. We also will test how patterns of brain activity related to cognitive performance differ in smokers and nonsmokers. Our long-term objectives are to provide information on how nicotine and smoking affect brain circuitry important to cognitive functions, and how these functions may differ in smokers and nonsmokers (either as effects of smoking or as etiological factors in nicotine dependence). Prior and ongoing studies have indicated that abstinence from smoking, nicotine administration, and even a history of smoking can affect performance on tests of cognitive control. Brain imaging studies with these tasks show activation of the dorsolateral prefrontal cortex (DLPFC) and the anterior cingulate cortex (ACC) as well as other brain regions. One such task is the Stroop Color-Word Interference Task, which requires focused attention and response inhibition while conflicting stimuli are presented. Performance of this task reliably activates ACC. Another test of cognitive control that shows possible effects of smoking is the N-Back Task, which requires working memory and generally produces activation of DLPFC. We will use functional magnetic resonance imaging (fMRI) to measure brain activation during performance of these two well-studied tasks. Our measure of regional activation in the brain will be change in magnetic resonance signal, representing relative hemodynamic change. We have two primary objectives. Our first specific aim is to determine the effects of smoking history and abstinence on brain function during performance of the N-Back Task and the Stroop Task. Smokers and nonsmokers will be tested with fMRI and cognitive activation. The smokers will be tested both in a state of satiety (after smoking ad libitum) as well as after 15-17 h of abstinence. Our second aim is to determine if smoking will reverse differences in brain activation and/or improve performance on the N-Back and Stroop tasks. Following each initial cognitive activation test session, both at satiety (after smoking ad libitum) and during abstinence, smokers will be allowed to smoke (ad libitum for 10 min) and will be re-tested. Nonsmokers, serving as controls, will be re-tested at corresponding times.