Neural substrates of cigarette craving, withdrawal, and relief: male-female differences

项目总结 在美国，吸烟是可预防的死亡和疾病的主要原因， 对男性和女性的健康风险。然而，女性比男性更容易受到一些负面因素的影响 吸烟对健康的影响，如心脏病，而且它们会经历一些性别特有的影响， 包括生育能力和月经功能改变、死产和宫颈癌。与男性相比，女性也 更难维持长期戒酒，并报告更大的渴望和戒断相关 苦恼(与吸烟有关的消极状态)。此外，吸烟对改善负面情绪的强化作用 状态(即，负强化)以及这种强化的预期可能会起到更大的作用 女性与男性在保持戒烟方面的失败。尽管这些消极的状态和 吸烟的缓解有助于复发，导致男性和女性差异的神经机制 这些行为状态仍然未知。了解它们可以帮助指导 个性化戒烟疗法，尤其是那些包括大脑刺激技术的戒烟疗法 关于大脑相关功能解剖学的知识。 因此，该项目的目标是推进男性的基础科学和临床/翻译研究。 女性在戒烟失败的重要决定因素上的差异--吸烟渴望，消极 戒烟期间的不良反应，以及恢复吸烟所产生的负面强化。男性和 女性，每日吸烟者(隔夜戒烟者)将在两个阶段进行测试，一次在他们之前，一次在他们之后 抽一天中的第一支烟。在吸烟前和吸烟后，参与者都将完成 自我报告测量吸烟渴望、戒烟和负面影响，并将进行持续测试 注意力是戒烟者的一种认知功能，戒烟后会受到损害，戒烟后会得到改善。 每个疗程还将包括静息状态下的功能磁共振成像以及与渴望诱导相结合的功能磁共振成像。 范例。休眠状态的功能连通性措施将重点放在已经被 与消极吸烟相关的状态有关。这些措施将包括基于种子的评估 与烟瘾有关的半岛连通性，以及相对连通性强度 大规模的大脑网络。在线索诱导的渴望过程中的大脑激活，这是一种预测 戒烟治疗的结果也将被检查。 这项工作的总体目标是确定观察到的男性和女性之间的神经基础 负性吸烟相关状态的差异及其吸烟缓解。这项工作将提供新颖的、批判性的 数据将促进我们对男性和女性差异的了解，并将为 个性化戒烟疗法。

PROJECT SUMMARY As the leading cause of preventable death and disease in the United States, smoking poses substantial health risks to men and women. However, women are more vulnerable than men to some of the negative health consequences of smoking, such as heart disease, and they experience some sex-specific effects, including altered fertility and menstrual function, stillbirth, and cervical cancer. Compared to men, women also have more difficulty maintaining long-term abstinence and report greater craving and withdrawal-related distress (negative smoking-related states). Moreover, the reinforcing effect of smoking to ameliorate negative states (i.e., negative reinforcement), as well as the expectancies of such reinforcement, may contribute more to the failure of women vs. men to maintain abstinence from smoking. Although these negative states and their relief by smoking contribute to relapse, the neural mechanisms driving the male-female differences in these behavioral states remain unknown. Understanding them can help guide the development of personalized smoking cessation therapies, especially those that include brain-stimulation techniques that rely on knowledge of relevant functional anatomy of the brain. The goal of this project, therefore, is to advance basic science and clinical/translational studies of male- female differences in important determinants of failure in smoking cessation – cigarette craving, negative states during withdrawal, and the negative reinforcement produced by resumption of smoking. Male and female, daily smokers (overnight abstinent) will be tested in two sessions, one before and one after they smoke the first cigarette of the day. In both the pre- and post-smoking sessions, the participants will complete self-report measures of cigarette craving, withdrawal and negative affect, and will perform a test of sustained attention, a cognitive function that is impaired in abstinent smokers and improved by resumption of smoking. Each session also will include fMRI both during the resting state and in conjunction with a craving-induction paradigm. Resting-state functional connectivity measures will focus on regions and circuits that have been linked with negative smoking-related states. These measures will include seed-based assessments of connectivity of the insula, which has been implicated in cigarette craving, and the relative connectivity strength of large-scale brain networks. Brain activation during cue-induced craving, a measure that is predictive of smoking-cessation treatment outcomes, will also be examined. The overall goal of this work is to identify neural substrates that underlie observed male-female differences in negative smoking-related states and their relief by smoking. This work will provide novel, critical data that will advance our knowledge of male-female differences, and will inform the development of personalized smoking cessation therapies.