NEUROCOGNITIVE PREDICTORS OF SMOKING CESSATION

描述（由申请方提供）：拟议研究的总体目标是确定对戒烟治疗敏感的神经生理学和行为标志物。虽然吸烟被广泛认为是主要的可预防的死亡原因，每年都有相当比例的吸烟者试图戒烟，但由于吸烟者在快速发展的戒断症状面前无法戒烟，戒烟尝试往往在第一周内失败。我们假设戒烟治疗的成功关键取决于认知控制过程的个体差异，这些过程在行为的抑制性调节中起着关键作用，包括反应抑制，动作监测和奖励/惩罚敏感性。我们进一步假设，这些过程受到急性尼古丁剥夺的影响，这有助于复吸。然而，在戒烟治疗的背景下，剥夺对认知控制过程的影响知之甚少，缺乏客观的生理和行为标志物，可以预测戒烟干预的敏感性是尼古丁成瘾转化研究的一个主要挑战。在拟议的研究中，我们将检查事件相关电位（ERP）和认知控制的行为措施作为戒烟干预敏感性的表型标志物的效用。参与者将是150名吸烟者，他们都将被激励接受认知行为戒烟治疗。具体目的是：1）检查认知控制和奖励敏感性的神经生理学和行为指标的基线个体差异对戒烟干预结果的影响，2）检查尼古丁剥夺对自我调节的神经认知指标的急性影响，并确定对这些影响的易感性的个体差异是否预测戒烟治疗的结果，和3）检查脑多巴胺系统中生物学相关的遗传变异对剥夺诱导的脑功能变化和戒烟治疗结果的影响。这项研究的潜在影响是双重的：首先，它将提供预测对行为干预敏感性的中间表型;其次，它将阐明介导尼古丁剥夺和吸烟复吸之间关系的神经认知机制。这些知识可用于开发更有效的戒烟治疗方法，并为最有可能受益的个人更好地定制特定治疗。该研究旨在确定戒烟干预结果的神经行为预测因素。该研究将检查参与戒烟治疗的吸烟者在戒烟前和戒烟后的行为自我控制的大脑功能，以确定大脑对尼古丁戒断反应的个体差异如何与行为变化（如冲动增加）相关，以及它们如何预测治疗结果（成功戒烟与复发）。这些知识可用于开发更有效的戒烟治疗方法，并为最有可能受益的个人更好地定制特定治疗。最终，与治疗敏感性相关的“神经行为特征”的知识可以导致个体化治疗计划的发展，例如那些强调行为或药物干预的计划，或者这些方法的某种组合。此外，识别严重影响戒烟结果的特定神经过程可以为药物干预提供新的靶点。

DESCRIPTION (provided by applicant): The overall goal of the proposed study is to identify neurophysiological and behavioral markers of sensitivity to smoking cessation treatment. Although smoking widely recognized as the major preventable cause of death and substantial proportion of smokers try to quit every year, quit attempts often fail within the first week due to smokers' inability to abstain from smoking in the face of rapidly developing withdrawal symptoms. We hypothesize that success of smoking cessation treatment critically depends on individual differences in the cognitive control processes that play a key role in inhibitory regulation of behavior including response inhibition, action monitoring, and reward/punishment sensitivity. We further hypothesize that these processes are compromised by acute nicotine deprivation, which facilitates relapse to smoking. However, little is known about the effects of deprivation on cognitive control processes in the context of smoking cessation treatment and the lack of objective physiological and behavioral markers that could predict the sensitivity to smoking cessation intervention is a major challenge in the translational research on nicotine addiction. In the proposed study, we will examine the utility of event-related potentials (ERPs) and behavioral measures of cognitive control as phenotypic markers of sensitivity to smoking cessation intervention. Participants will be 150 smokers all of whom will be motivated to receive cognitive-behavioral smoking cessation treatment. Specific Aims are 1) to examine the effects of baseline individual differences in neurophysiological and behavioral indices of cognitive control and reward sensitivity on the outcome of smoking cessation intervention, 2) to examine acute effects of nicotine deprivation on neurocognitive indicators of self-regulation and to determine whether individual differences in susceptibility to these effects predict the outcome of smoking cessation treatment, and 3) to examine the effects of biologically relevant genetic variation in the brain dopamine system on deprivation-induced changes in brain function and the outcome of smoking cessation treatment. Potential impact of the study is two-fold: first, it will provide intermediate phenotypes that predict sensitivity to behavioral interventions; second, it will elucidate neurocognitive mechanisms mediating the relationship between nicotine deprivation and smoking relapse. This knowledge can be used for the development of more efficient smoking cessation treatment approaches and for better tailoring of specific treatments to individuals who are most likely to benefit. The proposed study is aimed at the identification of neurobehavioral predictors of the outcome of a smoking cessation intervention. The study will examine brain function underlying self-control of behavior in smokers participating in a smoking cessation treatment, both before quitting and after quitting, in order to determine how individual differences in brain responses to nicotine abstinence are associated with changes in behavior such as increased impulsivity, and how they predict the outcome of treatment (successful quitting versus relapse). This knowledge can be used for the development of more efficient smoking cessation treatment approaches and for better tailoring of specific treatments to individuals who are most likely to benefit. Ultimately, the knowledge of "neurobehavioral profiles" associated with sensitivity to treatment can lead to the development of individualized treatment plans, e.g. those emphasizing behavioral or pharmacological intervention, or some combination of these approaches. Furthermore, identification of specific neural processes that critically affect the outcome of smoking cessation can suggest new targets for pharmacological intervention.