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

• 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
• 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

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.

项目总结/摘要 进食障碍（艾德）的病因复杂，但在很大程度上是未知的，导致严重缺乏有效的治疗。 治疗和“护理危机”。ED的共同点是进食动机的改变，从极端的 食物限制和体重减轻，暴饮暴食加上补偿策略，如自我诱导呕吐。 尽管传统上强调基于这些身体症状的诊断鉴别， 重叠，并且，沿着具有显著的诊断交叉（例如，从神经性厌食症到神经性贪食症） 时间，建议共同的特点，没有很好地捕捉到目前的诊断标准。受限的持久性 进食、暴饮暴食和/或排泄，尽管有负面后果，沿着改变奖励的证据， 艾德的惩罚敏感性，提出了一个问题，是否未能适当地处理和/或学习 奖励和/或惩罚的经历可能会导致反复采用适应不良的方法， 回避行为和疾病维持。这是第一项应用多维框架的研究 奖励处理艾德，通过检查如何相互作用的RDoC为基础的积极效价措施的“喜欢” (i.e.,奖励消费的享乐影响），“想要”或激励显著性（即，追求A的动机 学习，学习，学习。获得奖励结果或有事项），这些或有事项与不同的 额纹状体神经回路，不同的艾德亚型和对应的临床症状在基线和一个 一年后。我们将研究150例人口统计学匹配的艾德女性患者（50例AN限制型（AN-R），50例AN-1型（AN-R））， 暴食/泻药型（AN-BP）、神经性贪食症（BN）50例和健康对照（HC）50例，年龄18-35岁。期间 在fMRI中，参与者将完成1）修改的货币激励延迟（MID）任务，以评估组间差异 在神经预期（“想要”）和接受（“喜欢”）的奖励和厌恶特定的障碍（口味）， 广义（金钱）刺激（目标1），和2）概率联想学习任务，以评估决策 以及从金钱得失中学习工具（目标2）。目标3将检查以下内容之间的互动 “喜欢”、“想要”和学习以及与研究开始时和1年后症状的关联。探索性 本研究旨在通过神经黑色素MRI（NM-MRI）检测多巴胺功能与艾德的相关性 诊断和大脑对“喜欢”、“想要”的反应，以及学习进一步告知奖励的机械模型 本研究的创新之处在于：（1）采用了多维度的研究框架， 奖励处理，以检查未充分研究的独立和互动的贡献，但至关重要的是 构建体（例如，“喜欢”，“想要”，学习）在艾德，2）它评估的作用，刺激方式（口味，金钱）和 “喜欢”和“想要”的效价，以及3）将这些结构与研究进入时的实际症状和行为联系起来 1年后，了解是什么驱动了共同和不同的症状，并预测症状的变化， 具有潜在的重大临床影响。识别潜在症状的维度结构 它们的神经相关性对于提高对艾德的机械理解和推进精确医学至关重要。