Neuropharmacology of Emotion-Cognition Interaction in Nicotine Dependence

描述（由申请人提供）：吸烟仍然是美国过早死亡的头号可预防原因。尽管有这些可避免的后果，但估计有60-90%的吸烟者在尝试戒烟后的第一年内有戒烟复吸的动机。研究表明，吸烟者复吸的两个主要原因是：1）减轻压力和/或减少负面影响; 2）增强或恢复认知。因此，了解戒烟对情感和认知过程的神经生物学基础可能会为烟草成瘾的性质和治疗提供新的和有价值的见解。这项建议的总体目标是确定功能神经解剖学的相关性的变化，在戒烟期间的情绪和执行大脑功能，并将这些变化与临床相关的变量。我们将使用功能磁共振成像测量性能和局部血氧水平的变化，同时吸烟者和非吸烟者完成一项旨在评估情绪刺激对新视觉目标检测的影响的任务。在吸烟者中，我们将检查当前药物状态对情绪处理和新奇感检测之间的相互作用的影响，方法是扫描参与者1）在吸了常规数量和品牌的香烟后（饱足条件）和2）在24小时戒烟后（剥夺条件）。这样做将提供一个评估如何撤回调制情绪信息处理的神经基板。来自非吸烟者的数据将使我们能够比较正常健康个体与吸烟者在情绪信息处理过程中的大脑活动。我们假设，剥夺吸烟者，当与消极的情绪干扰，将表现出增加功能磁共振成像信号相对于吸烟饱腹感的大脑区域的基础1）视觉信息处理（外纹皮层），2）注意力（例如，前扣带皮层），3）情感信息的评估（例如，后扣带皮层），和4）边缘/奖赏区（例如，杏仁核）。我们进一步假设，负面情绪干扰会破坏后续新的视觉目标的处理。这种破坏的程度将是最大的剥夺吸烟者，这表明戒断导致更大的干扰执行功能的竞争情绪过程。这项研究的结果将增强我们对烟草戒断的神经生物学基础的理解，为治疗开发提供信息，并产生额外的假设和研究计划。公共卫生相关性：这项研究的结果将增强我们对烟草戒断的神经生物学基础的理解，为治疗开发提供信息，并产生额外的假设和研究计划。

DESCRIPTION (provided by applicant): Cigarette smoking remains the number one preventable cause of premature death in the U.S. In spite of these avoidable consequences, an estimated 60-90% of smokers motivated to attempt to quit relapse within the first year of their attempt. Research suggests that two of the primary reasons smokers relapse is 1) to attenuate stress and/or reduce negative affect and 2) to enhance or restore cognition. Therefore, understanding the neurobiological basis of smoking abstinence on affective and cognitive processes may provide new and valuable insights into the nature and treatment of tobacco addiction. The overarching objective of this proposal is to identify functional neuroanatomical correlates of changes in emotional and executive brain function during smoking abstinence, and to relate these changes to clinically relevant variables. We will measure changes in performance and regional blood oxygenation levels using fMRI while smokers and non-smokers complete a task designed to assess the effects of emotional stimuli on the detection of novel visual targets. In smokers, we will examine the effects of current drug state on the interaction between emotional processing and novelty detection by scanning participants 1) after smoking their regular number and brand of cigarettes (satiated condition) and 2) after 24 hr abstinence (deprived condition). Doing so will provide an assessment of how withdrawal modulates the neural substrates of emotion information processing. Data from non-smokers will allow us to compare brain activity during emotional information processing in normal healthy individuals with brain activity in smokers. We hypothesize that deprived smokers, when presented with negative emotional distractors will exhibit increased fMRI signal relative to smoking satiety in brain regions underlying 1) visual information processing (extrastriate cortex), 2) attention (e.g., anterior cingulate cortex), 3) evaluation of emotional information (e.g., posterior cingulate cortex), and 4) limbic/reward areas (e.g., amygdala). We further hypothesize that negative emotional distractors will disrupt processing of subsequent novel visual targets. The magnitude of this disruption will be greatest among deprived smokers, suggesting that withdrawal leads to greater interference of executive functioning by competing emotional processes. The results of this study will enhance our understanding of the neurobiological basis of tobacco withdrawal, inform treatment development, and generate additional hypotheses and research plans. PUBLIC HEALTH RELEVANCE: The results of this study will enhance our understanding of the neurobiological basis of tobacco withdrawal, inform treatment development, and generate additional hypotheses and research plans.