NEUROCOGNITIVE PREDICTORS OF SMOKING CESSATION

戒烟的神经认知预测因素

• 批准号: 7941737
• 负责人: Andrey P. Anokhin
• 金额: $ 38.46万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7941737
• 关键词: Abstinence; Acute; Affect; Anterior; Behavior; Behavior Therapy; Behavioral; Biological Assay; Brain; Catechol O-Methyltransferase; Cause of Death; Characteristics; Cognitive; Data; Development; Electrophysiology (science); Event; Event-Related Potentials; Face; Feedback; Functional Magnetic Resonance Imaging; Genetic Polymorphism; Genetic Variation; Genotype; Goals; Impairment; Impulsivity; Individual; Individual Differences; Informal Social Control; Intervention; Knowledge; Lead; Link; Literature; Measurable; Mediating; Monitor; Neurobiology; Neurocognition; Neurocognitive; Neurosciences Research; Nicotine; Nicotine Dependence; Outcome; Participant; Performance; Phenotype; Physiological; Play; Predisposition; Prefrontal Cortex; Probability; Process; Punishment; Regulation; Relapse; Rewards; Role; Self-control as a personality trait; Smoke; Smoker; Smoking; Smoking Cessation Intervention; Translational Research; Treatment outcome; Withdrawal Symptom; Withholding Treatment; base; behavior measurement; cognitive control; cognitive neuroscience; deprivation; dopamine system; falls; indexing; meetings; methionylmethionine; neurobehavioral; neurophysiology; relating to nervous system; response; smoking cessation; smoking relapse; success; treatment planning; valylvaline

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.

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学和行为标志物。尽管吸烟被广泛认为是可预防的主要死亡原因，并且每年都有相当大比例的吸烟者尝试戒烟，但由于吸烟者面对迅速发展的戒断症状而无法戒烟，戒烟尝试往往在第一周内失败。我们假设戒烟治疗的成功主要取决于认知控制过程的个体差异，认知控制过程在行为的抑制性调节中发挥关键作用，包括反应抑制、行动监控和奖励/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，从而促进吸烟的复吸。然而，人们对戒烟治疗中剥夺对认知控制过程的影响知之甚少，并且缺乏可以预测戒烟干预敏感性的客观生理和行为标记，是尼古丁成瘾转化研究的主要挑战。在拟议的研究中，我们将检查事件相关电位（ERP）和认知控制行为测量作为戒烟干预敏感性表型标记的效用。参与者将是 150 名吸烟者，他们都将有动力接受认知行为戒烟治疗。具体目标是 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可以预测戒烟治疗的结果，3）检查大脑多巴胺系统中生物学相关的遗传变异对剥夺引起的变化的影响大脑功能和戒烟治疗的结果。该研究的潜在影响有两方面：首先，它将提供预测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具体治疗方法。拟议的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相关，例如增加冲动，以及他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具体治疗方法。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制定，例如那些强调行为或药物干预或这些方法的某种组合的方法。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目标。