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》（FTA）对香烟包装上图形警告标签（GWL）的要求。根据《自由贸易协定》，GWL将包括九个强制性文字警告中的一个，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，食品和药物管理局的证据表明，一般的GWL有效，特别是GWL产生强烈的情绪唤起，不足以证明侵权行为是正当的。具体而言，法院指出，缺乏数据支持GWL在减少实际吸烟方面的有效性。该裁决强调了GWL现有数据的局限性，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，即在说服性健康传播中，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的方法，从临床和神经生理学的角度来解决这个问题。我们将使用生物化学（尿可替宁水平）和神经成像（功能性磁共振成像，fMRI）检测以及传统的说服措施，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使用情绪反应（ER）量表为最终规则选择GWL。我们将研究150名非寻求治疗的吸烟者对GWL的大脑反应，并监测他们在4周长时间暴露于携带高或低ER GWL的真实香烟包装之前和之后的尿液可替宁水平。基于我们的初步数据，我们假设暴露于高ER GWL的吸烟者比暴露于低ER GWL的吸烟者表现出更大的UC降低。根据我们的初步数据和先前的文献指出，mPFC和杏仁核作为关键的对手的大脑区域介导的视听反吸烟广告的大脑反应，我们假设，急性暴露于高ER GWL将与较高的杏仁核和mPFC的反应比低ER GWL。此外，我们预测杏仁核对GWL的反应将在4周的自然暴露于GWL后下降，而mPFC反应将增加，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4周暴露期前后香烟渴望、每日摄入量和大脑fMRI对视觉香烟线索的反应的变化。通过将大脑（fMRI），行为（可替宁水平），说服力和动机（对戒烟的态度和意图）的测量应用于现实生活中暴露于不同情感水平GWL的一组吸烟者，该项目将提供综合结果，以补充现有的人口水平数据，并为平衡宪法和公共卫生利益的科学驱动的卷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.