Response Training for Obesity Treatment: Translational Neuroscience

摘要 肥胖每年导致30万美国人死亡，但大多数治疗方法并不能持久减肥。的人 对高热量食物，大脑奖赏和注意区域反应更强，抑制区域反应更弱 食物图像/线索显示了将来体重增加的增加（Demos等人，2012; Stice等人，2015; Yokum等人，2011, 2014），与暴饮暴食是对高热量食物的强烈接近反应的结果的理论一致 与弱抑制反应配对的线索（Wiers等人，2007年）。这意味着，减少 奖励和注意区域的反应，这样的食物，并增加抑制控制区的反应，应 减少暴饮暴食，这是植根于暴露于无处不在的食物线索。基于计算机的反应抑制 用高热量食物训练减少了对训练食物的注意偏差和摄入，增加了对训练食物的注意偏差和摄入。 抑制控制，并在3个概念验证试验中使超重参与者体重减轻， 持续6个月随访（Allom & Mullan，2015; Kemps等人，2014 b; Lawrence等人，2015年b; Veling 例如，2014）。一项初步试验发现，超重/肥胖的成年人谁完成了多方面的4小时反应- 高热量食物图像的抑制训练和低热量食物图像的反应促进训练 显示出降低fMRI评估的奖励和注意力区域对高热量训练食物的反应， 比完成严格的4小时一般反应-抑制/反应- 使用非食物图像的促进训练（d=.95），在4周内使多余的体脂减少7% 期我们建议评估这种反应训练干预的改进和扩展版本。目标1是 将180名超重/肥胖成人随机分为4周反应训练肥胖治疗组或一般抑制组， 培训控制条件，包括两个月的互联网交付助推器培训一年和一个智能 一款手机反应训练应用程序，可以在受到高热量食物诱惑时使用， 术前、术后和3个月、6个月和12个月随访时（例如，%体脂，主要结果）。目的二是使用功能磁共振成像 为了测试是否减少奖励和注意区域反应，以及增加抑制区域反应， 在反应训练中使用和不使用的高热量食物图像介导了干预对 减肥我们还将测试在训练期间参与者是否表现出奖励和注意力的急剧减少 区域反应，并增加对高热量训练食物图像的抑制反应，以捕捉 学习过程，评估干预对训练中未使用的食物图像的普遍性，并收集 关于中介的行为数据。目标3是测试干预效果是否会对那些表现出 对高热量食物图像的抑制性控制较少，多巴胺的遗传倾向 奖励回路中的信号，更大的预测试奖励和注意区域反应，更弱的抑制 区域反应高热量的食物图像，根据理论，反应训练是更有效的 那些有强烈的pre-potent方法倾向于高热量食物。

ABSTRACT Obesity causes 300,000 US deaths yearly, but most treatments do not result in lasting weight loss. People who show greater brain reward and attention region response, and less inhibitory region response, to high-calorie food images/cues show elevated future weight gain (Demos et al., 2012; Stice et al., 2015; Yokum et al., 2011, 2014), consistent with the theory that overeating results from a strong approach response to high-calorie food cues paired with a weak inhibitory response (Wiers et al., 2007). This implies that an intervention that reduces reward and attention region response to such food and increases inhibitory control region response should reduce overeating that is rooted in exposure to pervasive food cues. Computer-based response-inhibition training with high-calorie foods has decreased attentional bias for and intake of the training food, increased inhibitory control, and produced weight loss in overweight participants in 3 proof-of-concept trials, with effects persisting through 6-mo follow-up (Allom & Mullan, 2015; Kemps et al., 2014b; Lawrence et al., 2015b; Veling et al., 2014). A pilot trial found that overweight/obese adults who completed a multi-faceted 4-hr response- inhibition training with high-calorie food images and response-facilitation training with low-calorie food images showed reduced fMRI-assessed reward and attention region response to high-calorie training foods and greater body fat loss than controls who completed a rigorous 4-hr generic response-inhibition/response- facilitation training with non-food images (d=.95), producing a 7% reduction in excess body fat over the 4-wk period. We propose to evaluate a refined and extended version of this response-training intervention. Aim 1 is to randomize 180 overweight/obese adults to a 4-wk response training obesity treatment or a generic inhibition training control condition that both include bi-monthly Internet-delivered booster training for a year and a smart phone response training app that can be used when tempted by high-calorie foods, assessing outcomes at pre, post, and at 3-, 6-, and 12-month follow-ups (e.g., % body fat, the primary outcome). Aim 2 is to use fMRI to test whether reduced reward and attention region response, and increased inhibitory region response to high-calorie food images used and not used in the response training mediate the effects of the intervention on fat loss. We will also test whether during training participants show acute reductions in reward and attention region response, and increases in inhibitory response to high-calorie training food images to capture the learning process, assess generalizability of the intervention to food images not used in training, and collect behavioral data on mediators. Aim 3 is to test whether intervention effects will be stronger for those who show less inhibitory control in response to high-calorie food images, a genetic propensity for greater dopamine signaling in reward circuitry, and greater pretest reward and attention region response, and weaker inhibitory region response to high-calorie food images, based on the theory that response training is more efficacious for those with a strong pre-potent approach tendency to high-calorie foods.