NEUROCOGNITIVE PREDICTORS OF SMOKING CESSATION

描述(由申请人提供)：拟议研究的总体目标是确定对戒烟治疗敏感的神经生理和行为标记物。尽管吸烟被广泛认为是主要的可预防的死亡原因，每年有相当比例的吸烟者试图戒烟，但由于吸烟者面对迅速发展的戒断症状无法戒烟，戒烟尝试往往在第一周失败。我们假设，戒烟治疗的成功关键取决于认知控制过程中的个体差异，认知控制过程在包括反应抑制、动作监控和奖惩敏感性在内的行为抑制调节中发挥关键作用。我们进一步假设，这些过程受到急性尼古丁剥夺的影响，这促进了吸烟的复发。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，缺乏能够预测戒烟干预敏感性的客观生理和行为标记物是尼古丁成瘾翻译研究的主要挑战。在这项拟议的研究中，我们将检验事件相关电位(ERPs)和认知控制的行为测量作为戒烟干预敏感性的表型标记物的实用性。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。具体目标是：1)检测基线个体认知控制和奖励敏感性的神经生理和行为指标差异对戒烟干预结果的影响；2)检测尼古丁剥夺对自我调节神经认知指标的急性影响，并确定对这些影响敏感性的个体差异是否可以预测戒烟治疗的结果；3)检测大脑多巴胺系统中与生物相关的基因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有两个：第一，它将提供预测行为干预敏感性的中间表型；第二，它将阐明调节尼古丁剥夺和吸烟复发之间关系的神经认知机制。这些知识可以用来开发更有效的戒烟治疗方法，并更好地为最有可能受益的个人定制具体的治疗方法。这项拟议的研究旨在确定戒烟干预结果的神经行为预测因素。这项研究将研究参与戒烟治疗的吸烟者在戒烟前和戒烟后对行为自我控制的大脑功能，以确定尼古丁戒断后大脑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)。这些知识可以用来开发更有效的戒烟治疗方法，并更好地为最有可能受益的个人定制具体的治疗方法。最终，对与治疗敏感性相关的“神经行为特征”的了解可以导致个性化治疗计划的发展，例如，那些强调行为或药物干预的治疗计划，或这些方法的某种组合。此外，对关键影响戒烟结果的特定神经过程的识别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.