Brain and behavioral effects of graphic cigarette warning labels

描述（由申请人提供）：最近的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（FTA）对卷烟包装上图形警告标签（gwl）的要求。根据自由贸易协定，全球健康警示标志将包括九种强制性文字警告中的一种，以及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根据第一修正案享有的权利。法院认为，FDA的证据表明，一般来说，gwl的有效性，特别是gwl产生强烈的情绪唤醒，不足以证明侵权的正当性。具体而言，法院指出，缺乏支持gwl在减少实际吸烟方面有效性的数据。这一裁决凸显了现有全球变暖数据的局限性，这些数据主要是通过使用自我报告结果测量方法的大规模调查获得的。此外，该裁决还触及了一个更基本的争议，即说服性健康传播中强烈突出的格式和内容的有效性背后的机制。该项目将采用独特的跨学科方法，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，来比较在情绪反应（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使用这些量表为其最终规则选择gwl。我们将研究150名未接受治疗的吸烟者对gwl的大脑反应，并监测他们在接触含有高ER gwl或低ER gwl的真实香烟包装4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 - GWLs的吸烟者比暴露于低ER - GWLs的吸烟者UC的减少幅度更大。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对手脑区域，我们假设急性暴露于高ER GWLs将与高杏仁核和mPFC反应相关，而不是低ER GWLs。此外，我们预测长时间自然暴露于高强度脑损伤后，杏仁核对高强度脑损伤的反应会下降，而mPFC的反应会增加，这两种效应在高ER组中更为突出。次要假设将评估急性mPFC反应对尿可替宁水平变化的预测价值，以及在4周暴露前后香烟渴望、每日摄入量和大脑功能磁共振成像对视觉香烟提示的反应的变化。通过对一群在现实生活中暴露于不同程度的gwl的吸烟者应用大脑（功能磁共振成像）、行为（可替宁水平）、说服和动机（对戒烟的态度和意图）的测量，该项目将提供综合结果，补充现有的人口水平数据，并为平衡宪法和公共卫生利益的科学驱动的香烟包装监管提供信息。

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.