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

项目总结 (家长奖) 在美国，吸烟是可预防的死亡和疾病的主要原因，而女性遭受的痛苦更大 吸烟的一些健康后果，如心脏病和宫颈癌。与男人相比，女人 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 驱动这种男女差异的大脑功能的差异仍然是未知的，对它们的理解 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，特别是背侧前扣带回皮质(DACC)可能 促进戒烟。吸烟者的dACC中谷氨酸(Glu)含量高于不吸烟者，并表现出 DACC Glu与默认模式网络中对吸烟相关线索的反应性呈正相关。vt.给出 这些发现和健康个体大脑谷氨酸水平的性别差异，对于检测男性是很重要的。 DACC Glu对戒断时的渴求和消极状态的影响及其缓解的性别差异 吸烟后，以及这些状态下的神经底物。 我们将把自我报告措施与磁共振波谱(MRS)和功能性相结合 磁共振成像(FMRI)解决三个特定目标：目标1.确定男性和女性的差异 戒烟期dACC中Glu信号与烟瘾和负性状态的关系 (消极情绪、心理退缩和焦虑)。目标2.确定男性和女性在 DACC中的Glu与吸烟引起的渴求缓解和消极状态(即消极状态)的关系 目的3.确定dACC中Glu与静息状态相关性的性别差异。 大规模神经网络内部和之间的状态功能连接性(RsFC)。这个项目的目标是 重点是吸烟前神经网络dACC和rsFC中的Glu评估；然而，吸烟前和吸烟后 将对60名吸烟者(30名男性和30名女性)进行吸烟评估(自我报告、功能磁共振成像和MRS)。 在隔夜(~12小时)戒断之后。女性将在两个单独的日子内完成这些评估， 卵泡期和黄体期，以评估月经周期和卵巢激素的影响。调查结果 有助于促进个性化的、针对性别的戒烟疗法的发展。

PROJECT SUMMARY (Parent Award) 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.