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

项目摘要 在美国，吸烟是可预防的死亡和疾病的主要原因， 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影响， 吸烟的健康后果，如心脏病，他们经历了一些性别特异性的影响， 包括生育能力和月经功能改变、死胎和宫颈癌。与男性相比，女性也 更难保持长期禁欲，并报告更大的渴望和戒断相关 消极吸烟状态（Negative Smoking Related States）此外，吸烟对改善负面影响的强化作用 各州（即，负强化），以及这种强化的预期，可能有助于更多 女性和男性在保持戒烟方面的失败。虽然这些负面的国家和 通过吸烟缓解症状会导致复发，这是导致男性和女性在吸烟方面存在差异的神经机制。 这些行为状态仍然未知。了解它们有助于指导 个性化的戒烟疗法，特别是那些包括大脑刺激技术， 大脑的相关功能解剖学知识。 因此，该项目的目标是推进男性生殖器疾病的基础科学和临床/转化研究， 女性在戒烟失败的重要决定因素方面的差异-香烟渴望，阴性 国家在撤出，并恢复吸烟产生的负强化。男性和 女性，每日吸烟者（过夜戒烟）将在两个阶段进行测试，一个在他们之前，一个在他们之后。 抽一天中的第一支烟。在吸烟前和吸烟后，参与者将完成 自我报告的香烟渴望，戒断和负面影响的措施，并将进行持续的测试 注意力，戒烟者的认知功能受损，恢复吸烟后得到改善。 每一个环节还将包括静息状态下的功能磁共振成像和与渴望诱导相结合的功能磁共振成像 范例静息状态下的功能连通性测量将侧重于已经被 与消极吸烟相关的国家。这些措施将包括基于种子的评估 与香烟渴望有关的大脑皮层的连接，以及相对连接强度 大规模的大脑网络。在线索诱导的渴望过程中，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神经基板的基础上观察到的男女 消极吸烟相关状态的差异及其通过吸烟的缓解。这项工作将提供新颖，关键 这些数据将促进我们对男女差异的了解，并为人类的发展提供信息 个性化的戒烟疗法。

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.