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

摘要 虽然美国3700万成年吸烟者中有一半每年试图戒烟，但估计只有3%的人 成功吸烟与大脑回路的变化有关，这些变化驱动激励显着性评估， 执行控制随着时间的推移，吸烟线索的激励显着性变得增强，而 不吸烟的奖励减少了。此外，执行控制吸烟的动机和驱动器成为 受损虽然功能性磁共振成像（fMRI）已经确定了大脑回路与 激励显着性估值和执行控制，我们目前对大脑如何 回路随着停止治疗和依赖性的减少而改变。变化的特点 戒烟期间的神经回路有可能告知有针对性的发展 神经药理学、行为和脑刺激停止干预。这项建议旨在提供 候选人与培训和研究，以解决这一关键差距，在我们的确定可修改的 吸烟依赖的神经标志物。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非常低的香烟，同时收集纵向fMRI测量超过3倍， 点MRI任务将涉及吸烟和不吸烟奖励的激励显著性评估， 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- 相关序列来测量吸烟气味线索反应性，这是一个研究不足，但潜在有效的次要指标。 吸烟的人。在烟草使用、人类嗅觉、功能磁共振成像和纵向研究方面， 分析和宾夕法尼亚州烟草监管科学中心的支持，候选人将出现 作为一名以病人为导向的临床研究人员， 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.