Error Sensitivity as a Predictor of Nicotine Withdrawal & Smoking Cessation

描述（由申请人提供）：戒烟困难和慢性复吸是许多吸烟者经历的特征，可能在很大程度上是由于神经机制的适应，这些机制调节奖赏、情感和目标导向行为，这些行为是反复吸毒的结果。最近关于尼古丁依赖的理论公式表明，这些动机系统在某些方面受到了损害，使个人的认知资源和行为对吸烟产生了偏见，即使有明确的戒烟目标。一般的认知控制和错误监测对于克服在这些条件下驱动吸烟行为的强有力的神经映射至关重要。本提案的具体目的是研究与使用行为咨询和透皮尼古丁贴片戒烟的吸烟者样本中错误监测相关的神经基质。本研究将利用电生理学（密集传感器阵列脑电图记录）来测量错误相关的负性（ERN），这是一种与事件相关的电位，可能在响应错误后发生在前扣带皮层（ACC）和前额叶皮层的相关区域。研究表明，ERN直接反映了中边缘多巴胺神经元的活动，其放电模式激活/抑制ACC并将事件编码为比预期“更糟”（犯错）或“更好”（获得奖励）的事件。有兴趣戒烟的吸烟者将在戒烟日期前参加两个平衡的实验室实验（一个被剥夺，一个非被剥夺），在实验中，他们将完成一个修改后的2选择侧卫任务。每次试验之后都会有反馈，表明参与者是否做出了正确、错误或延迟的反应。在一半的实验中，正确的实验之后会有积极激励的图片（性爱情侣的图片），错误的实验之后会有中性的图片（动物的图片）；在另一半中，正确的反应将是中性的图像（植物），不正确的反应是消极的激励图像（残害）。吸烟者将在第二次脑电图评估后进入戒烟治疗，包括咨询和尼古丁替代。该设计将使我们能够梳理出方法（奖励）动机和回避动机对行为（错误）监控系统效率的相对影响及其与禁欲的关系。我们预测尼古丁剥夺将改变ERN的效果：可能会增加积极试验的错误监测和/或减少消极激励试验的错误监测。预计在剥夺或动机条件之间表现出最小ERN下降的个体在治疗结束时将有更高的戒断率。这项研究的结果将提高我们对与吸烟者的奖励、影响和认知控制相关的神经生物学系统的理解，为理论提供信息，并可能有助于未来旨在戒烟期间使这些系统正常化的干预措施。公共卫生相关性：许多吸烟者经历的戒烟困难和慢性复发在很大程度上可能是由于神经机制的适应，这些机制调节奖赏、情感和目标导向行为，这些行为是反复吸毒的结果。本研究将使用ERP（事件相关电位）的ERN（错误相关负性）成分来确定方法（奖励）动机和回避动机对行为（错误）监测系统效率的相对影响及其与戒断的关系。我们预测尼古丁剥夺将改变ERN的效果：可能会增加积极试验的错误监测和/或减少消极激励试验的错误监测。预计在剥夺或动机条件之间表现出最小ERN下降的个体在治疗结束时将有更高的戒断率。这项研究的结果将提高我们对与吸烟者的奖励、影响和认知控制相关的神经生物学系统的理解，为理论提供信息，并可能有助于未来旨在戒烟期间使这些系统正常化的干预措施。

DESCRIPTION (provided by applicant): The difficulty quitting and chronic relapse which characterize the experience of many smokers may be due in large measure to the adaptations in neural mechanisms regulating reward, affect, and goal- directed behavior that have taken place as a consequence of repeated drug use. Recent theoretical formulations of nicotine dependence have suggested that these motivational systems have been compromised in ways that bias the individual's cognitive resources and behavior towards smoking, even with the explicit goal to quit. Cognitive control in general and error monitoring specifically is critical to overcoming the potent neural mappings that drive smoking behavior under these conditions. The specific aims of this proposal are to study neural substrates related to error monitoring in a sample of smokers attempting to quit using behavioral counseling and the transdermal nicotine patch. This study will utilize electrophysiological (dense sensor array EEG recording) to measure the error-related negativity (ERN), an event-related potential likely generated in the anterior cingulate cortex (ACC) and related areas of the pre-frontal cortex that occurs following a response error. Studies suggest that the ERN directly reflects the activity of mesolimbic dopamine neurons, whose firing patterns activate/inhibit the ACC and encode events as events as being "worse" (making an error) or "better" (receiving a reward) than expected. Smokers interested in quitting will participate in two counterbalanced laboratory sessions (one deprived and one non-deprived) prior to their quit date in which they will complete a modified 2-choice flanker task. Each trial will be followed by feedback indicating whether the participant initiated a correct, incorrect, or late response. In half of the trials, correct trials will be followed by positively motivating images (pictures of erotic couples) and incorrect by neutral images (pictures of animals); in the other half, correct responses will be followed by neutral images (plants) and incorrect by negatively motivating images (mutilations). Smokers will enter smoking cessation therapy consisting of counseling and nicotine replacement following the second EEG assessment. The design will enable us to tease apart the relative impact of approach (reward) and avoidance motivation on the efficiency of the behavioral (error) monitoring system and its relation to abstinence. We predict that nicotine deprivation will alter the effects of the ERN: potentially increasing error monitoring on positive trials and/or decreasing error monitoring on negatively motivating trials. It is expected that individuals showing the smallest decrease in the ERN between either deprivation or motivational conditions will have higher abstinence rates at the end of treatment. The results of this study will improve our understanding of the neurobiological systems associated with reward, affect, and cognitive control among smokers by informing theory and potentially contributing to future interventions aimed at normalizing these systems during cessation. PUBLIC HEALTH RELEVANCE: The difficulty quitting and chronic relapse which characterize the experience of many smokers may be due in large measure to the adaptations in neural mechanisms regulating reward, affect, and goal-directed behavior that have taken place as a consequence of repeated drug use. This study will use the ERN (error related negativity) component of the ERP (event related potential) to determine the relative impact of approach (reward) and avoidance motivation on the efficiency of the behavioral (error) monitoring system and its relation to abstinence. We predict that nicotine deprivation will alter the effects of the ERN: potentially increasing error monitoring on positive trials and/or decreasing error monitoring on negatively motivating trials. It is expected that individuals showing the smallest decrease in the ERN between either deprivation or motivational conditions will have higher abstinence rates at the end of treatment. The results of this study will improve our understanding of the neurobiological systems associated with reward, affect, and cognitive control among smokers by informing theory and potentially contributing to future interventions aimed at normalizing these systems during cessation.