Brain and behavioral effects of graphic cigarette warning labels

描述(由申请人提供)：最近的一项上诉法院裁决撤销了FDA的最终规则，该规则实施了2009年家庭吸烟预防和烟草控制法案(FTA)对香烟包装上图形警告标签(GWL)的要求。根据FTA的说法，GWL将包括九个强制性文本警告中的一个，以及一张说明吸烟对健康负面影响的图片。法院裁定，FDA选择的GWL侵犯了烟草公司原告的第一修正案权利。法院认为，FDA关于全球工作日志总体上有效的证据，特别是产生强烈情感唤起的全球工作日志，不足以证明侵权是正当的。具体地说，法院注意到缺乏数据支持GWL在减少实际吸烟方面的有效性。这项裁决突显了现有GWL数据的局限性，这些数据主要是通过使用自我报告结果衡量的大规模调查获得的。此外，这项裁决还触及了一个更基本的争议，即在有说服力的健康沟通中，强烈突出的格式和内容的有效性背后的机制。这个项目将采取一种独特的跨学科方法，从临床和神经生理学的角度来解决这个问题。我们将使用生化(尿可替宁水平)和神经成像(功能磁共振成像，fMRI)分析，以及传统的说服措施，来比较情绪反应(ER)量表上被评为高或低的GWL对大脑和生物行为(尿可替宁)的影响，FDA使用该量表来选择GWL作为其最终规则。我们将研究150名未接受治疗的吸烟者对GWL的大脑反应，并监测他们在暴露于真实生活中携带高或低ER GWL的香烟包四周之前和之后的尿可替宁水平。根据我们的初步数据，我们假设暴露于高ER GWL的吸烟者将比暴露于低ER GWL的吸烟者表现出更大的UC减少。根据我们的初步数据和先前的文献指出，mPFC和杏仁核是调节大脑对视听禁烟广告反应的关键脑区，我们假设，急性暴露于高ER GWL将与高ER GWL比低ER GWL产生更高的杏仁核和mPFC反应相关。此外，我们预测，在自然暴露于GWL 4周后，杏仁核对GWL的反应将下降，而mPFC反应将增加，这两种影响在高ER组更加突出。第二个假设将评估急性mPFC反应对尿可替宁水平变化的预测价值，以及在暴露4周之前和之后对香烟视觉线索的渴望、日常摄入量和脑功能磁共振反应的变化。通过将大脑(功能磁共振成像)、行为(可替宁水平)、说服和动机(戒烟态度和戒烟意图)的测量应用于在现实生活环境中暴露于不同情感水平的GWL的吸烟者队列，该项目将提供综合结果，以补充现有的人口水平数据，并为平衡宪法法律和公共健康利益的香烟包装科学驱动的监管提供信息。

DESCRIPTION (provided by applicant): A recent appellate court ruling has vacated the FDA's Final Rule that implemented the 2009 Family Smoking Prevention and Tobacco Control Act (FTA) requirement of graphic warning labels (GWLs) on cigarette packs. According to the FTA, the GWLs are to include one of nine mandatory textual warnings and a picture illustrating the negative health effects of smoking. The court decided that the GWLs selected by the FDA infringed on the tobacco company plaintiffs' First Amendment rights. The court opined that FDA's evidence of effectiveness of GWLs in general and GWLs producing strong emotional arousal in particular was insufficient to justify the infringement. Specifically, the court noted te lack of data supporting the effectiveness of GWLs in reducing actual smoking. The ruling highlights the limitations of existing data on GWLs that have been obtained predominantly through large-scale surveys using self-report outcome measures. In addition, the ruling has touched on a more basic controversy on the mechanisms underlying the effectiveness of strongly salient format and content in persuasive health communications. This project will take a unique trans- disciplinary approach to address this issue from both a clinical and neurophysiological perspective. We shall use biochemical (urine cotinine levels) and neuroimaging (Functional Magnetic Resonance Imaging, fMRI) assays, as well as traditional measures of persuasion, to compare the brain and bio-behavioral (urine cotinine) impact of GWLs that were rated high or low on the emotional response (ER) scale, used by the FDA to select GWLs for its Final Rule. We shall study 150 non-treatment seeking smokers' brain response to GWLs and monitor their urine cotinine levels, before and after a 4-week long exposure to real-life cigarette packs carrying High or Low ER GWLs. Based on our preliminary data, we hypothesize that smokers exposed to high ER GWLs will exhibit larger reductions in UC than those exposed to low ER GWLs. Based on our preliminary data and prior literature pointing to the mPFC and the amygdala as key opponent brain regions mediating the brain response to audio-visual anti-smoking ads, we hypothesize that acute exposure to high ER GWLs will be associated with higher amygdala and mPFC response than low ER GWLs. In addition, we predict that the amygdala response to GWLs will decline after 4-week long naturalistic exposure to GWLs, while mPFC response will increase, with both effects more prominent in the High ER group. Secondary hypotheses will evaluate the predictive value of acute mPFC response on urine cotinine levels change, as well changes in cigarette craving, daily intake, and brain fMRI response to visual cigarette cues prior to and after the 4-week exposure period. By applying measures of brain (fMRI), behavior (cotinine levels), persuasion and motivation (attitudes and intentions towards smoking quitting) to a cohort of smokers exposed to different affective levels of GWLs in a real-life setting, the project will provide integrated results that would complement existing population-level data and inform science-driven regulation of cigarette packaging that balances constitutional law and public health interest.