Devaluing Energy-Dense Foods for Cancer Control: Translational Neuroscience

7.摘要 肥胖和摄入某些食物会增加患癌症的风险，但最常见的治疗方法(行为体重 减肥计划)很少能带来持久的减肥和饮食行为的改变，显然是因为卡路里 限制增加了食物的奖励价值，并促使人们做出节约能源的适应。干预措施 降低致癌风险食品(如红肉、精制糖)的隐含价值可能更有效。 新出现的数据表明，行为反应训练和认知重新评估训练降低了对 这类食物会导致这些食物的摄入量减少，从而减轻体重。内部化激励价值是 反映在腹内侧前额叶/眶前叶皮质评估系统(VmPFC)中，该系统编码 这是食物的隐性奖励价值，是维持不健康饮食的强化循环的核心。因此， Vmpfc估值系统是一个有希望的干预目标，因为系统的变化可能 打乱不健康的增援循环。有趣的是，各种干预通过以下方式影响vmPFC 不同的路径。行为训练改变了对评估区域的运动输入，而认知训练依赖于 在外侧前额叶“自上而下”的区域。拟议的翻译神经科学实验将比较 两种新疗法导致食品价值持久变化的疗效，以及 以理论为基础的相关过程中的基线个体差异(如反应倾向和认知 风格)治疗效果适中。我们将随机选择300名有进食风险的超重/肥胖成年人- 以及肥胖相关癌症对健康食品和远离癌症风险的行为反应训练 食物，侧重于癌症风险食物的认知重新评估干预，或非食物抑制控制培训。 目的1比较这两种干预措施降低股票估值的效果和作用机制。 与主动控制条件相关的致癌食物，使用神经、行为、自我报告和生理 对过程和结果的衡量。目标2是建立影响的时间模式和持久性 食物的摄入量和习惯、体脂、BMI和腰臀比将在实验前、实验后和实验结束时测量。 6个月和12个月的随访。AIM 3使用机器学习来构建和验证低成本、易于管理的 一种综合预测个体是否以及在多长时间内可能对干预做出反应，以及 治疗。我们假设，自我报告措施具体与估值有关(例如，支付意愿) 以及特定于干预的评估路径(例如，行为反应倾向、认知风格) 预测差异反应。发现这些个体差异将提供一个实用、低成本的工具来 帮助干预者将一个特定的人与该人的有效治疗“配对”。这个项目非常 创新是因为没有研究直接比较这些治疗方法的不同和共同影响 评估，使用大脑成像来研究影响的机制，测试这些干预是否产生 食物价值和体脂的持久变化，或者建立和验证一个缓和反应的复合体。

7. Abstract Obesity and intake of certain foods increases cancer risk, but the most common treatment (behavioral weight loss programs) rarely produces lasting weight loss and eating behavior change, apparently because caloric restriction increases the reward value of food and prompts energy-sparing adaptations. Interventions that reduce the implicit valuation of cancer-risk foods (e.g., red meats, refined sugar) may be more effective. Emerging data suggest that behavioral response training and cognitive reappraisal training reduce valuation of such foods, which leads to decrease intake of these foods and weight loss. Internalized incentive value is reflected in a ventromedial prefrontal/orbitofrontal cortex valuation system (“vmPFC”), which encodes the implicit reward value of food and is central to a reinforcement cycle that perpetuates unhealthy eating. Thus, the vmPFC valuation system is a promising target for intervention because changes to the system might disrupt the unhealthy reinforcement cycle. Interestingly, various interventions influence the vmPFC through distinct pathways. Behavioral training alters motor input to valuation regions, whereas cognitive training relies on lateral prefrontal “top-down” regions. The proposed translational neuroscience experiment will compare the efficacy with which two novel treatments cause lasting change in food valuation, and whether a composite of theory-based baseline individual differences in relevant processes (such as response tendencies and cognitive styles) moderate treatment effects. We will randomize 300 overweight/obese adults who are at risk for eating- and obesity-related cancers to behavioral response training toward healthy foods and away from cancer-risk foods, a cognitive reappraisal intervention focused on cancer-risk foods, or non–food inhibitory control training. Aim 1 compares the efficacy and mechanisms of action of these two interventions to reduce valuation of cancer-risk foods relative to the active control condition, using neural, behavioral, self-report, and physiological measures of the process and outcomes. Aim 2 is to establish the temporal pattern and durability of the effects across time ; food intake and habits , body fat, BMI, and waist-to-hip ratio will be measured pre, post, and at 3-, 6-, and 12-month follow-up. Aim 3 uses machine learning to build and validate a low-cost, easy-to-administer composite that predicts whether and for how long an individual is likely to respond to intervention, and to which treatment. We hypothesize that self-report measures specifically related to valuation (e.g., willingness-to-pay) and to intervention-specific pathways to valuation (e.g., behavioral response tendencies, cognitive style) will predict differential response. Discovering these individual differences will provide a practical, low-cost tool to help interventionists “match” a given person to an effective treatment for that person . This project is very innovative because no study has directly compared the distinct and common effects of these treatments on valuation, used brain imaging to study the mechanism of effects, tested whether these interventions produce a lasting change in food valuation and body fat, or built and validated a composite that moderates response .