Identifying circuit-level neuromarkers of smoking dependence that change in response to intervention

摘要 尽管美国每年3700万成年吸烟者中有一半试图戒烟，但估计只有3%的人正在戒烟 成功。吸烟与大脑回路的变化有关，大脑回路驱动激励性显著估值和 执行控制。随着时间的推移，吸烟线索的激励突显变得更强，而吸烟提示的激励突显 不吸烟的奖励减少了。此外，对吸烟动机和驱动力的行政控制变得 受伤了。虽然功能磁共振成像(FMRI)已经确定了与 激励显著评价和高管控制，我们目前对大脑如何 随着戒烟治疗和依赖性的减少，电路也会发生变化。描述中的变化 戒烟过程中的神经回路有可能通知靶向发展 神经药理学、行为学和脑刺激停止干预。这项提案旨在提供 应聘者需要经过培训和研究，以解决我们在确定可修改的 吸烟依赖的神经标记物。候选人将进行一项为期6周的双盲随机试验 吸烟者中尼古丁含量极低的香烟，同时收集纵向fMRI测量超过3次- 积分。核磁共振任务将包括对吸烟和不吸烟奖励的激励显著评估，以及 通过抑制和决策进行执行控制。这些任务将包括呼吸触发事件- 测量吸烟气味线索反应性的相关序列，这是一个研究较少但潜在有效的次要因素 吸烟增强剂。与烟草使用、人类嗅觉、功能磁共振成像和纵向 在宾夕法尼亚州立烟草监管科学中心的分析和支持下，候选人将浮出水面 作为一名以患者为中心的临床研究人员，他为我们对吸烟的神经行为理解做出了贡献 依赖和烟草使用。

Abstract Although half of the 37 million adult smokers in the US attempt to quit each year, only an estimated 3% are successful. Smoking is associated with changes in brain circuitry that drive incentive salience valuation and executive control. Over time, the incentive salience of smoking cues become enhanced, while the salience of non-smoking rewards are diminished. Further, executive control over smoking motivation and drives becomes impaired. While functional magnetic resonance imaging (fMRI) has identified brain circuitry associated with incentive salience valuation and executive control, we currently have a limited understanding of how this brain circuitry changes with cessation treatment and reductions in dependence. Characterizing changes in neurocircuitry during smoking cessation has the potential to inform the development of targeted neuropharmacological, behavioral, and brain stimulation cessation interventions. This proposal aims to provide the candidate with training and research to address this critical gap in our identification of modifiable neuromarkers of smoking dependence. The candidate will conduct a double-blind, 6-week, randomized trial of very low nicotine content cigarettes among smokers while collecting longitudinal fMRI measures over 3 time- points. The MRI tasks will engage incentive salience valuation of smoking and non-smoking rewards and executive control through inhibition and decision making. These tasks will include a respiration-triggered-event- related sequence to measure smoking odor cue reactivity, an understudied, but potentially potent secondary smoking reinforcer. With a mentorship team of experts in tobacco use, human olfaction, fMRI, and longitudinal analysis and the support of the Penn State Tobacco Center of Regulatory Science, the candidate will emerge as a patient-oriented clinical researcher contributing to our neurobehavioral understanding of smoking dependence and tobacco use.