Dynamic Neural Computations Underlying Cognitive Control in Bulimia Nervosa

神经性贪食症认知控制下的动态神经计算

• 批准号: 10638708
• 负责人: Laura A. Berner
• 金额: $ 82.02万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-15 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10638708
• 关键词: Acute; Adult; Behavior; Behavioral; Behavioral Research; Binge Eating; Brain; Bulimia; Cessation of life; Characteristics; Choice Behavior; Chronic; Chronic Disease; Clinical; Cognitive; Computer Models; Corpus striatum structure; Cost Control; Data; Decision Making; Diffusion; Disease; Dorsal; Eating; Eating Disorders; Ecological momentary assessment; Elements; Failure; Fasting; Functional Magnetic Resonance Imaging; Goals; Hyperphagia; Impairment; Impulsivity; Individual; Intake; Intervention; Laboratories; Lateral; Learning; Matched Group; Measures; Metabolic; Modeling; Nature; Neurocognitive; Outcome; Patient Self-Report; Patients; Prefrontal Cortex; Probability; Process; Prognostic Marker; Psychiatry; Psychotic Disorders; Research; Resistance; Role; Sampling; Satiation; Scanning; Severities; Signal Transduction; Standardization; Statistical Methods; Symptoms; Testing; Time; Training; Update; Ventral Striatum; Woman; Work; behavioral economics; behavioral response; clinically significant; cognitive control; cognitive neuroscience; computational neuroscience; cost; dietary restriction; disability; discount; discounting; expectation; experience; follow-up; food consumption; ideal observer (Bayesian); innovation; medical complication; multimodality; neural; neuroimaging; neuroregulation; novel; premature; process improvement; purge; response; smartphone based assessment; substance use; trait

PROJECT SUMMARY/ABSTRACT Bulimia nervosa (BN) is a disabling and often chronic eating disorder associated with medical complications and premature death. There is an acute need to identify the mechanisms that maintain BN and that may serve as targets for new treatments. Most studies have assumed that BN is perpetuated by stable, trait-like factors, including self-reported impulsivity and deficits in the ability to exert cognitive control. However, the out-of-control excessive intake and compensatory behaviors characteristic of BN are episodic and tend to alternate with periods of restricted intake or even fasting, suggesting intermittent oscillations in control. In addition, emerging work in behavioral economics and cognitive neuroscience suggests that failures to ultimately exert cognitive control depend on numerous neural computations, including: updating predictions about whether control will be needed in the next moment, and deciding whether trying to exert control is worth the costly cognitive effort. The overarching goal of this R01 is to clarify how these cognitive control computations may fluctuate across fasted and fed states in BN, potentially maintaining the cyclical nature of the disorder. Specifically, the proposed study combines functional magnetic resonance imaging (fMRI), computational modeling, and real-time mobile assessments to examine whether food consumption abnormally impairs frontostriatal function and associated control-related updating and effort-valuation processes in BN. We propose that the impairment of these processes in the fed state and relative improvement of these processes in the fasted state perpetuate out-of- control binge/purge episodes alternating with periods of dietary restriction. We will compare behavioral and neural responses of women with BN to those of group-matched healthy women during an inhibitory control paradigm to assess control-related prediction updating (Aim 1) and during a cognitive effort discounting paradigm to assess control-related effort valuation (Aim 2) in two states: after a 16-h fast and after a standardized meal. Aim 3 will use multi-modal symptom measures to examine main effects and potential interactions of state-specific updating and valuation processes on binge eating, purging, and restriction severity at baseline and at 6-month follow-up. The research team includes experts in BN-focused research, neuroimaging, computational neuroscience and psychiatry, advanced statistical methods, and ecological momentary assessment. The project innovatively 1) applies a neurocomputational framework to examine the roles of understudied subcomponents of cognitive control in BN; 2) assesses the influence of metabolic state (fasted, fed) on these subcomponents; and 3) relates the dynamics of these subcomponents in the laboratory to real-world, state-specific experiences and symptoms at baseline and over time. Data from this project will pinpoint altered elements of the control process that may represent prognostic biomarkers. Results will also identify the potential optimal patient state (i.e., fasted or fed) for control-focused interventions. Therefore, this study will yield vital data to inform urgently needed, precisely targeted treatments for cycles of binge eating, purging, and restriction.

项目概要/摘要 神经性贪食症 (BN) 是一种致残且通常是慢性的饮食失调症，与医疗并发症和 过早死亡。迫切需要确定维持 BN 的机制，并可作为 新治疗的目标。大多数研究都假设 BN 是由稳定的、类似特质的因素维持的， 包括自我报告的冲动和认知控制能力缺陷。然而，失控的 BN 的过度摄入和补偿行为特征是间歇性的，并且往往与 限制摄入甚至禁食的时期，表明控制的间歇性波动。此外，新兴的 行为经济学和认知神经科学的研究表明，未能最终发挥认知能力 控制取决于大量的神经计算，包括： 更新关于控制是否会被执行的预测 并决定是否值得付出昂贵的认知努力来施加控制。这 R01 的总体目标是阐明这些认知控制计算在禁食期间如何波动 以及国阵的联邦州，可能会维持这种混乱的周期性。具体来说，拟议的研究 结合了功能磁共振成像 (fMRI)、计算建模和实时移动 评估食物消耗是否异常损害额纹状体功能及相关 BN 中与控制相关的更新和工作量评估流程。我们建议对这些资产进行减值 进食状态下的过程以及禁食状态下这些过程的相对改进使非- 控制暴饮暴食/清除事件与饮食限制期间交替进行。我们将比较行为和 在抑制控制期间，BN 女性与分组匹配的健康女性的神经反应 评估控制相关预测更新（目标 1）和认知努力折扣范式的范式 在两种状态下评估与控制相关的努力评估（目标 2）：禁食 16 小时后和标准化膳食后。 目标 3 将使用多模式症状测量来检查特定州的主要影响和潜在相互作用 基线和 6 个月时暴食、清除和限制严重程度的更新和评估流程 后续行动。研究团队包括以 BN 为重点的研究、神经影像、计算等方面的专家 神经科学和精神病学、先进的统计方法和生态瞬时评估。项目 创新地 1）应用神经计算框架来检查未充分研究的子组件的作用 BN 中的认知控制； 2) 评估代谢状态（禁食、进食）对这些子成分的影响； 3) 将实验室中这些子组件的动态与现实世界、特定州的经验联系起来 以及基线和一段时间内的症状。该项目的数据将精确定位控件的更改元素 可能代表预后生物标志物的过程。结果还将确定潜在的最佳患者状态 （即禁食或进食）以进行以控制为重点的干预措施。因此，这项研究将产生重要数据，以紧急通知 针对暴饮暴食、清除和限制的循环，需要精确的针对性治疗。