Food Avoidance in Anorexia Nervosa-A Test of Generalization Mechanisms

项目总结 神经性厌食症(AN)是一种破坏性的疾病，其死亡率是所有精神科疾病中最高的。 生病了。目前的治疗方法往往是不充分的，而且没有任何药理药物被证明有效。更好的 对AN的病理生理学理解是非常必要的。避免高脂肪食物是一个核心问题 行为障碍导致AN的发病率和死亡率，但对其潜在的原因知之甚少 认知和神经机制。焦虑和对脂肪的恐惧被认为起到了重要作用：患有 一般来说，AN高度焦虑，这种焦虑的主要焦点是与食物或饮食有关的。极端 食物回避和围绕食物的焦虑在一个机械的框架中被很好地记录下来 对这些现象及其关系的理解还没有得到严格的研究。建议数 研究测试了一种潜在的潜在的持续避免高卡路里、高脂肪的新机制 食物-对食物避免的过度概括-并利用了计算和计算方面的最新进展 认知神经科学来解释这一机制。使用一种新的范式，我们可以将 避免行为，量化威胁和安全信号的学习和概括。我们的具体目标是 研究支持回避行为泛化的神经和认知机制。我们会 使用功能磁共振成像(FMRI)和计算建模来表征 健康对照受试者(HC)，当恐惧时如何概括积极的回避行为 结果是电击(厌恶AN和HC)和高脂肪食物(厌恶AN)。我们的中心预测是 与避免震惊相比，患有ANS的人在避免食物时会更广泛地概括，而且 这将与1)涉及脑岛、纹状体和杏仁核的大脑回路的活动有关，2)与现实世界有关 避免高卡路里、高脂肪食物。该研究提出了一种新的机制来解释严重的 AN中的不适应进食行为，已被证明非常难以治疗。计算技术在计算机中的应用 神经科学工具将允许对认知和神经机制进行更精确的说明 水平，这对于确定新的治疗靶点，表征疾病的生物标志物是必不可少的 脆弱性和轨迹，以及更广泛的翻译研究。这项研究将为 大规模R01，以研究这些机制的开发以及开发和测试 临床试验中的基于机制的治疗。

PROJECT SUMMARY Anorexia nervosa (AN) is a devastating disorder with a mortality rate among the highest of any psychiatric illness. Current treatments are often inadequate, and no pharmacologic agents have proven effective. A better understanding of the pathophysiology of AN is greatly needed. Avoidance of high-fat food is a central behavioral disturbance contributing to morbidity and mortality of AN, yet little is known about the underlying cognitive and neural mechanisms. Anxiety and fear of fat are thought to play important roles: individuals with AN are highly anxious in general, with the primary focus of this anxiety being food or eating related. Extreme food avoidance and anxiety surrounding food are well documented in AN, yet a mechanistic framework for understanding these phenomena and their relationship has not been rigorously studied. The proposed research tests a novel mechanism potentially underlying the persistent avoidance of high-calorie, high-fat food—excessive generalization of food avoidance—and leverages recent advances in computational and cognitive neuroscience to elucidate this mechanism. With the use of a novel paradigm, we can operationalize avoidance behavior and quantify learning and generalization of threat and safety signals. Our specific aim is to examine the neural and cognitive mechanisms supporting generalization of avoidance behavior in AN. We will use functional magnetic resonance imaging (fMRI) and computational modeling to characterize, in AN and healthy comparison participants (HC), how active avoidance behavior is generalized both when the feared outcome is electric shock (aversive to AN and HC) and high-fat food (aversive to AN). Our central prediction is that individuals with AN will generalize more broadly when avoiding food than when avoiding shock, and that this will be related to 1) activity in brain circuits involving the insula, striatum, and amygdala and 2) real-world avoidance of high-calorie, high-fat food. The study proposes a novel mechanism to account for the severely maladaptive eating behavior in AN, which has proven very difficult to treat. The application of computational neuroscience tools will allow for more precise specification of mechanisms at both the cognitive and neural levels, which is essential for identifying novel treatment targets, characterizing biomarkers of illness vulnerability and trajectory, and translational research more broadly. This study will create a foundation for a large-scale R01 to investigate these mechanisms developmentally and development and testing of mechanism-based treatments in clinical trials.