Neural Substrates of Cigarette Craving, Withdrawal, and Relief: Male-Female Differences

在美国，吸烟是可预防的死亡和疾病的主要原因，而女性的比例更高 吸烟会带来一些健康后果，如心脏病和宫颈癌。与男人相比， 女性经历更强烈的戒断症状，更难维持长期戒断 吸烟和戒烟治疗对男性和女性的帮助并不相同。潜在的差异 在驱动这些男性和女性差异的大脑功能方面仍不清楚，了解它们可以指导 个性化戒烟疗法的发展。 谷氨酸能神经传递是戒烟治疗的一个有希望的靶点，但男性-女性 可能影响谷氨酸能治疗效果的差异尚未得到调查。减少 突起网络内的谷氨酸水平，特别是背侧前扣带皮质(DACC)的谷氨酸水平可能有助于 戒烟。吸烟者的dACC中谷氨酸(Glu)含量高于不吸烟者，并表现出阳性 DACC Glu与默认模式网络中对吸烟相关线索的反应性的相关性。考虑到这些 健康人大脑谷氨酸水平的发现和性别差异，重要的是检测男女之间的 DACC Glu对戒断时渴求和负性状态的影响及戒断后缓解的差异 吸烟，以及构成这些状态的神经底物。 我们将把自我报告措施与磁共振波谱(MRS)和功能磁共振相结合 磁共振成像(FMRI)旨在解决三个特定目标：目的1.确定男性和女性在 在戒烟期间，dACC中的Glu信号与吸烟渴望和消极状态(消极影响， 心理退缩和焦虑)。目的2.确定男性和女性在谷氨酸关联性上的差异 DACC，可缓解吸烟引起的渴求和消极状态(即，消极强化)；以及目标3。 确定dACC中Glu与静息状态功能连接性相关性的性别差异 (RsFC)在大规模神经网络内部和之间。该项目的目标集中在吸烟前评估上 在神经网络的dACC和rsFC中的Glu；然而，吸烟前和吸烟后的评估(自我报告，功能磁共振， 60名吸烟者(30名男性和30名女性)将在隔夜(~12小时)戒烟后完成MRS。女人会的 在卵泡期和黄体期分别在两天内完成这些评估，以便评估 月经周期和卵巢激素的影响。 这一发现有助于推动个性化、针对性别的戒烟疗法的发展。 相关性(请参阅说明)： 谷氨酸能神经传递是戒烟治疗的一个有希望的靶点，但男性和女性之间存在差异， 哪些因素会影响谷氨酸能治疗的疗效，还没有得到调查。我们将结合自我报告 用磁共振波谱和功能磁共振成像来确定性别的方法 大脑谷氨酸与戒烟、吸烟相关的内部状态的差异-- 诱导这些状态的缓解，以及这些状态下的神经基质。这些发现有助于推动 开发个性化的、针对性别的戒烟疗法。

Smoking is the leading cause of preventable death and disease in the U.S., and women disproportionately suffer some health consequences of smoking, such as heart disease and cervical cancer. Compared to men, women experience stronger withdrawal symptoms and have more difficulty maintaining long-term abstinence from smoking, and smoking-cessation treatments are not equally helpful to men and women. The underlying differences in brain function that drive these male-female differences remain unknown, and understanding them can guide development of personalized smoking-cessation therapies. Glutamatergic neurotransmission is a promising target for smoking cessation therapy, but male-female differences that can impact the efficacy of glutamatergic treatments have not been investigated. Reducing glutamate levels within the Salience Network, especially in the dorsal anterior cingulate cortex (dACC) may facilitate smoking cessation. Smokers have higher glutamate (Glu) in the dACC than nonsmokers and exhibit a positive correlation of dACC Glu with reactivity within the default-mode network to smoking-related cues. Given these findings and sex differences in brain glutamate levels in healthy individuals, it is important to test for male-female differences in the influence of dACC Glu on craving and negative states during withdrawal and their relief after smoking, as well as the neural substrates that underlie these states. We will combine self-report measures with magnetic resonance spectroscopy (MRS) and functional magnetic resonance imaging (fMRI) to address three specific aims: Aim 1. Determine male-female differences in the association of Glu signal in the dACC with cigarette craving and negative states during abstinence (negative affect, psychological withdrawal, and anxiety). Aim 2. Determine male-female differences in the association of Glu in the dACC with smoking-induced relief of craving and negative states (i.e., negative reinforcement); and Aim 3. Determine male-female differences in the association of Glu in the dACC with resting-state functional connectivity (rsFC) within and between large-scale neural networks. The aims of this project focus on pre-smoking assessments of Glu in the dACC and rsFC of neural networks; however, pre- and post-smoking assessments (self-report, fMRI, and MRS) will be completed in 60 smokers (30 men and 30 women) after overnight (~12h) abstinence. Women will complete these assessments on 2 separate days, during the follicular and luteal phases, to allow evaluation of menstrual-cycle and ovarian hormone effects. The findings can help advance development of personalized, sex-specific smoking cessation therapies. RELEVANCE (See instructions): Glutamatergic neurotransmission is a promising target for smoking cessation therapy, but male-female differences, which can impact the efficacy of glutamatergic treatments, have not been investigated. We will combine self-report measures with magnetic resonance spectroscopy and functional magnetic resonance imaging to determine sex differences in the association of brain glutamate with internal states linked to cigarette withdrawal, with smoking- induced relief of these states, and the neural substrates that underlie them. The findings can help advance development of personalized, sex-specific, smoking-cessation therapies.