Devaluing Energy-Dense Foods for Cancer Control: Translational Neuroscience

7.摘要 肥胖和摄入某些食物会增加癌症风险，但最常见的治疗方法（行为体重） 减肥计划）很少产生持久的减肥和饮食行为的改变，显然是因为热量 限制增加了食物的奖励价值，并促进了节省能量的适应。的干预措施 降低癌症风险食品的隐含价值（例如，红肉，精制糖）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，从而导致这些食物的摄入量减少和体重减轻。内在激励价值是 反映在腹内侧前额叶/眶额皮质评价系统（“vmPFC”）中，其编码 食物的隐性奖励价值，是一个强化循环的核心，使不健康的饮食永久化。因此，在本发明中， vmPFC评估系统是一个有希望的干预目标，因为系统的变化可能 打破不健康的强化循环。有趣的是，各种干预措施通过以下方式影响vmPFC 不同的路径。行为训练改变运动输入到评价区域，而认知训练依赖于 在侧前额叶“自上而下”的区域。拟议的转化神经科学实验将比较 两种新的治疗方法引起食物价值持久变化的功效，以及 基于理论的基线相关过程的个体差异（如反应倾向和认知 风格）温和的治疗效果。我们将随机抽取300名超重/肥胖的成年人，他们有吃- 和肥胖相关的癌症对健康食品和远离癌症风险的行为反应训练 食物，认知重新评估干预，重点是癌症风险的食物，或非食物抑制控制培训。 目的1比较了这两种干预措施的疗效和作用机制，以减少对 癌症风险的食物相对于积极控制条件，使用神经，行为，自我报告，和生理 过程和结果的衡量。目的2是建立影响的时间模式和持久性 随时间变化;将在术前、术后和第3天测量食物摄入量和习惯、体脂、BMI和腰臀比， 6个月和12个月随访。Aim 3使用机器学习来构建和验证一个低成本、易于管理的 一种预测个体是否以及在多长时间内可能对干预做出反应的复合物，以及对哪些干预做出反应的复合物。 治疗我们假设，自我报告措施具体涉及到估值（例如，支付意愿） 以及干预特定的估值途径（例如，行为反应倾向，认知风格）将 预测差异响应。发现这些个体差异将提供一种实用的、低成本的工具， 帮助干预者将特定患者与针对该患者的有效治疗“匹配”。这个项目很 创新，因为没有研究直接比较这些治疗的独特和共同影响， 评估，使用大脑成像来研究效果的机制，测试这些干预措施是否会产生 食物价值和身体脂肪的持久变化，或者建立和验证一个缓和反应的复合物。

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 .