NICOTINE WITHDRAWAL, SMOKING & COGNITION: AN FMRI STUDY

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 每年可归因于尼古丁依赖的死亡人数超过了所有非法药物滥用的总和。其原因和机制包括社会因素、生理因素和认知因素。虽然对认知的影响是吸烟的主要原因是值得怀疑的，但关于人们吸烟原因的自我报告表明，这些影响是重要的贡献者。这项工作的广泛目标是阐明吸烟和戒烟对认知的影响所涉及的神经回路。我们将测试参与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方面的不同。认知控制指的是指导自愿的、复杂的行动的大脑功能。我们还将测试吸烟者和不吸烟者大脑活动与认知表现相关的模式有何不同。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大脑回路的信息，以及这些功能在吸烟者和不吸烟者中的差异(无论是作为吸烟的影响还是作为尼古丁依赖的病因)。先前和正在进行的研究表明，戒烟、服用尼古丁，甚至吸烟史都会影响认知控制测试的表现。这些任务的脑成像研究显示，背外侧前额叶皮质(DLPFC)和前扣带回皮质(ACC)以及其他脑区都处于激活状态。其中一项任务是Stroop颜色词干扰任务，它需要集中注意和反应抑制，同时呈现冲突的刺激。这项任务的执行可靠地激活了ACC。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。我们将使用功能磁共振成像(FMRI)来测量这两个经过充分研究的任务执行过程中的大脑激活情况。我们对大脑区域激活的测量将是磁共振信号的变化，代表相对血流动力学的变化。我们有两个主要目标。我们的第一个具体目标是确定在N-back任务和Stroop任务的执行过程中，吸烟史和戒烟史对大脑功能的影响。吸烟者和不吸烟者将接受功能磁共振成像和认知激活测试。吸烟者将在饱腹感(随意吸烟后)和戒烟15-17小时后接受测试。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。在每次最初的认知激活测试之后，无论是在饱腹期(随意吸烟后)还是在戒烟期间，吸烟者都将被允许吸烟(随意吸烟10分钟)，并将重新进行测试。作为对照的非吸烟者将在相应的时间进行重新检测。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.