Incentive Processing and Learning in Anorexia Nervosa and Bulimia Nervosa

神经性厌食症和神经性贪食症的激励处理和学习

基本信息

批准号：
10573214
负责人：
CHRISTINA E WIERENGA
金额：
$ 75.51万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-02-15 至 2027-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10573214
关键词：
Address Adopted Adult Anorexia Nervosa Association Learning Behavior Behavioral Binge Eating Biological Markers Body Weight decreased Brain Bulimia Caring Chronic Classification Clinical Clinical Treatment Complex Computer Models Consumption Corpus striatum structure Coupled Dangerousness Data Decision Making Diagnosis Diagnostic Dimensions Disease Dopamine Eating Eating Disorders Etiology Exhibits Failure Functional Magnetic Resonance Imaging Functional disorder Heterogeneity Impairment Incentives Learning Machine Learning Magnetic Resonance Imaging Maintenance Measures Mental disorders Modality Modeling Motivation Operant Conditioning Outcome Participant Patients Performance Positive Valence Process Psychological reinforcement Psychopathology Punishment Research Domain Criteria Rewards Role Signal Transduction Stimulus Substantia nigra structure Sucrose Symptoms System Taste Perception Tea Testing Time Vomiting Woman aged approach behavior avoidance behavior clinical predictors diagnostic criteria diagnostic strategy dietary restriction disorder subtype effective therapy experience financial incentive food restriction hedonic improved incentive salience innovation medical complication mortality neural neural circuit neural correlate neuromelanin new therapeutic target novel physical symptom precision medicine predictive marker psychosocial purge response reward processing targeted treatment therapy development

项目摘要

PROJECT SUMMARY/ABSTRACT The etiology of eating disorders (ED) is complex, yet largely unknown, resulting in a profound lack of effective treatments and a “crisis in care”. Common to EDs are alterations in the motivation to eat, ranging from extreme food restriction and weight loss, to binge eating coupled with compensatory strategies like self-induced vomiting. Despite the traditional emphasis on diagnostic differentiation based on these physical symptoms, they often overlap, and, along with significant diagnostic crossover (e.g., from anorexia nervosa to bulimia nervosa) over time, suggest shared features that are not well captured by current diagnostic criteria. Persistence of restricted eating, binge eating and/or purging despite negative consequences, along with evidence of altered reward and punishment sensitivity in ED, raise the question of whether a failure to appropriately process and/or learn from rewarding and/or punishing experiences might contribute to repeated engagement in maladaptive approach and avoidance behavior and illness maintenance. This is the first study to apply a multi-dimensional framework of reward processing to ED, by examining how the interplay of RDoC-based Positive Valence measures of `liking' (i.e., the hedonic impact of reward consumption), `wanting' or incentive salience (i.e., motivation to pursue a reward), and learning (i.e., the acquisition of reward-outcome contingencies), which are associated with distinct frontostriatal neurocircuitry, differ across ED subtype and correspond to clinical symptoms at baseline and one year later. We will study 150 demographically-matched women with ED (50 AN-restricting type (AN-R), 50 AN- binge eating/purging type (AN-BP), 50 bulimia nervosa (BN)) and 50 healthy controls (HC) aged 18-35. During fMRI, participants will complete 1) a modified monetary incentive delay (MID) task to assess group differences in both neural anticipation (`wanting') and receipt (`liking') of rewarding and aversive disorder-specific (taste) and generalized (money) stimuli (Aim 1), and 2) a probabilistic associative learning task to assess decision-making and instrumental learning from monetary wins and losses (Aim 2). Aim 3 will examine interactions between `liking', `wanting' and learning and associations with symptoms at study entry and 1 year later. An Exploratory Aim will examine associations of dopamine function, as measured by neuromelanin MRI (NM-MRI), with ED diagnosis and brain response to `liking', `wanting', and learning to further inform mechanistic models of reward in ED. This study is innovative and significant in several ways: 1) it adopts a multi-dimensional framework of reward processing to examine independent and interactive contributions of understudied, yet critically important constructs (e.g., `liking', `wanting', learning) in ED, 2) it assesses the role of stimulus modality (taste, money) and valence in `liking' and `wanting', and 3) relates these constructs to actual symptoms and behavior at study entry and 1 year later to understand what drives shared and divergent symptoms and predicts symptom change, which has potential for substantial clinical impact. Identification of dimensional constructs underlying symptoms and their neural correlates is critical to improve a mechanistic understanding of ED and advance precision medicine.

项目概要/摘要饮食失调（ED）的病因很复杂，但很大程度上未知，导致严重缺乏有效性治疗和“护理危机”是急诊科常见的饮食动机改变的情况，从极端到极端。食物限制和减肥，暴饮暴食加上自我催吐等补偿策略。尽管传统上强调根据这些身体症状进行诊断鉴别，但它们经常重叠，并且伴随着显着的诊断交叉（例如，从神经性厌食症到神经性贪食症）时间，建议当前诊断标准未能很好地捕获的共享特征。尽管有负面后果，仍进食、暴饮暴食和/或清除，并有奖励和奖励的证据 ED 中的惩罚敏感性，提出了是否未能适当处理和/或从中学习的问题奖励和/或惩罚的经历可能会导致反复采取不适应的方法和这是第一个应用多维框架的研究。通过检查基于 RDoC 的正价衡量“喜欢”的相互作用如何对 ED 进行奖励处理（即奖励消费的享乐影响）、“想要”或激励显着性（即追求某种目标的动机）奖励）和学习（即获得奖励结果意外事件），这与不同的额纹状体神经回路，根据 ED 亚型的不同而不同，并且与基线时的临床症状和一种一年后，我们将研究 150 名人口统计匹配的 ED 女性（50 名 AN 限制型 (AN-R)，50 名 AN- 型）。暴食/通便型 (AN-BP)、50 名神经性贪食症 (BN) 和 50 名 18-35 岁的健康对照 (HC) 期间。 fMRI，参与者将完成 1) 修改后的货币激励延迟 (MID) 任务以评估群体差异在神经预期（“想要”）和接受（“喜欢”）奖励和厌恶障碍特定（味觉）和广义（金钱）刺激（目标 1），以及 2）评估决策的概率联想学习任务从金钱收益和损失中进行工具性学习（目标 3）将研究两者之间的相互作用。研究开始时和一年后的“喜欢”、“想要”和学习以及与症状的关联。 Aim 将通过神经黑色素 MRI (NM-MRI) 测量多巴胺功能与 ED 之间的关系诊断和大脑对“喜欢”、“想要”的反应，并学习为进一步的奖励机制模型提供信息这项研究在几个方面具有创新性和意义：1）它采用了多维框架奖励处理，以检查未被充分研究但至关重要的独立和交互式贡献 ED 中的建构（例如“喜欢”、“想要”、学习），2）评估刺激方式（品味、金钱）的作用，以及 “喜欢”和“想要”的效价，以及3）将这些结构与研究开始时的实际症状和行为联系起来一年后，了解是什么驱动了共同和不同的症状并预测症状变化，这具有对潜在症状和维度结构的识别产生重大临床影响的潜力。它们的神经关联对于提高对 ED 的机制理解和推进精准医学至关重要。