Reward Systems and Food Avoidance in Adolescents with Low Weight Eating Disorders

低体重饮食失调青少年的奖励制度和食物避免

• 批准号: 9334942
• 负责人: THOMAS B HILDEBRANDT
• 金额: $ 59.42万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-19 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9334942
• 关键词: Acute; Adolescence; Adolescent; Affective; Amygdaloid structure; Anorexia Nervosa; Behavior; Behavior Therapy; Behavioral; Biological; Brain; Brain region; Characteristics; Chronic; Clinical; Control Groups; Corpus striatum structure; Cues; Data; Dimensions; Disease; Down-Regulation; Eating; Eating Behavior; Eating Disorders; Electromyography; Emotions; Exposure to; Extinction (Psychology); Family; Food; Food Aversion; Functional Magnetic Resonance Imaging; Future; Hypersensitivity; Impairment; Incentives; Individual; Insula of Reil; Intervention; Laboratories; Learning; Maps; Measures; Mental disorders; Modeling; Neurobiology; Neurons; Palate; Panic Disorder; Pathologic; Patients; Physiological; Population; Population Intervention; Positioning Attribute; Prefrontal Cortex; Process; Psyche structure; Psychophysiology; Public Health; Regulation; Research Domain Criteria; Resistance; Reversal Learning; Rewards; Safety; Stimulus; System; Target Populations; Testing; Ventral Striatum; Visceral; Weight; Weight Gain; Work; addiction; adolescent patient; base; behavior measurement; causal model; conditioning; contingency management; experience; mortality; neuroimaging; novel; pleasure; prevent; reinforcer; response; restoration; theories; treatment response

Project Summary Low weight eating disorders are severe psychiatric disorders that most often develop in adolescence, have a chronic course, and evidence poor response to treatment. A core feature of these disorders is food avoidance; which can be conceptualized in the research domain criteria (RDoC) framework as dysregulation in the dimensional expression of acute threat (i.e., food aversion) and reward learning (i.e., pleasurable response to food absence). Emerging neuroimaging evidence suggests that deficits in insula-amygdala-ventral striatum (IAVS) neurocircuitry contribute to individual variability in aversive and reward learning, and that these brain regions demonstrate abnormal responses to food/eating stimuli. Our pilot data suggest that patients with low weight eating disorder (LW-ED) experience difficulty extinguishing food-cue associations in a reversal learning paradigm compared to healthy controls, a difficulty that is related to psychophysiological measures of aversive- disgust (not fear). Additionally, our data indicate the presence of a pleasure response to food avoidance or ‘cued safety’ that may further impair reversal of food-cue associations because it prevents reappraisal of the threatening stimuli. We have also successfully piloted an interoceptive exposure intervention for this population that targets visceral sensitivity and seeks to increase ‘top-down’ regulation of the IAVS neurocircuit. This intervention is distinguishable from existing contingency management based behavioral interventions that are standard for this population and target the reward value of food and eating. Further, simultaneously acquired fMRI-electromyography(EMG) pilot data from our team suggests that an elevated aversive-disgust response is associated with increased connectivity between insula and amygdala, and the cued absence of the food reward is associated with elevated connectivity between amygdala and ventral striatum that is associated with elevated pleasure response. The proposed project will (a) use novel fMRI-EMG to test the relationship between effective connectivity within amygdala-insula-ventral striatum network and its relationship to psychophysiological and behavioral measures of acute threat and reward learning in 60 adolescents with LW- EDs and 30 healthy controls, (b) test the sensitivity of this network to an experimental interoceptive exposure paradigm relative to patients receiving family based therapy for weight restoration using dynamic causal modeling of fMRI-EMG data pre-post experimental conditions, (c) validate this model against objective measures of laboratory and real world eating behavior. The results of this study will help us better understand the core neurocircuitry that underlies both threat processing and reward/aversive learning and how this circuit relates to objective behavior. Further, we will determine the modifiability of this neurocircuitry via two distinct behavioral interventions chosen to target different aspects of affective processing and reward learning. These data will be used to inform future clinical interventions targeting aversive/reward learning within this population and dysregulation in insula-amygdala-ventral striatum subcircuits.

项目概要 低体重饮食失调是一种严重的精神疾病，最常见于青春期，具有 慢性病程，并且证据表明对治疗反应不佳。这些疾病的一个核心特征是避免进食。 这可以在研究领域标准（RDoC）框架中概念化为 急性威胁（即食物厌恶）和奖励学习（即对食物的愉快反应）的维度表达 食物缺失）。新出现的神经影像学证据表明岛叶-杏仁核-腹侧纹状体的缺陷 （IAVS）神经回路有助于厌恶和奖励学习的个体差异，并且这些大脑 区域表现出对食物/饮食刺激的异常反应。我们的试点数据表明，患有低血压的患者 体重进食障碍（LW-ED）在逆转学习中难以消除食物线索关联 与健康对照相比，这一范式的困难与厌恶的心理生理测量有关 厌恶（不是恐惧）。此外，我们的数据表明存在对避免食物或食物的愉悦反应。 “提示安全性”可能会进一步损害食物提示关联的逆转，因为它阻止了对食物提示的重新评估 威胁性刺激。我们还为此成功地试点了内感受暴露干预 以内脏敏感性为目标并寻求增强 IAVS 神经回路“自上而下”调节的人群。 这种干预措施与现有的基于应急管理的行为干预措施不同。 是该人群的标准，并以食物和饮食的奖励价值为目标。进一步地，同时 从我们团队获得的功能磁共振成像肌电图 (EMG) 试点数据表明，厌恶厌恶情绪升高 反应与岛叶和杏仁核之间的连接性增强有关，并且提示缺乏 食物奖励与杏仁核和腹侧纹状体之间的连接性增强有关 具有较高的愉悦反应。拟议的项目将 (a) 使用新颖的 fMRI-EMG 来测试这种关系 杏仁核-岛叶-腹侧纹状体网络内的有效连接及其与 60 名患有 LW- 的青少年的急性威胁和奖励学习的心理生理和行为测量 ED 和 30 名健康对照，(b) 测试该网络对实验性内感受暴露的敏感性 相对于接受基于家庭的体重恢复治疗的患者使用动态因果关系的范例 实验条件前后的功能磁共振成像-肌电图数据建模，(c) 根据目标验证该模型 实验室和现实世界饮食行为的测量。这项研究的结果将帮助我们更好地了解 威胁处理和奖励/厌恶学习的核心神经回路以及该回路如何 与客观行为有关。此外，我们将通过两个不同的方法来确定该神经回路的可修改性 针对情感处理和奖励学习的不同方面选择的行为干预措施。这些 数据将用于为未来针对该人群的厌恶/奖励学习的临床干预提供信息 以及岛-杏仁核-腹侧纹状体亚回路的失调。