Dynamic Neural Computations Underlying Cognitive Control in Bulimia Nervosa

项目总结/摘要 神经性贪食症（BN）是一种致残的慢性饮食失调，与医疗并发症有关， 过早死亡迫切需要确定维持BN的机制，并可能作为 新疗法的目标。大多数研究都假设BN是由稳定的、类似特质的因素延续的， 包括自我报告的冲动和认知控制能力的缺陷。然而，失控的 BN的过量摄入和代偿行为特征是偶发性的，并且倾向于与 限制摄入甚至禁食的时期，表明控制的间歇性振荡。此外，新兴 行为经济学和认知神经科学的研究表明， 控制依赖于许多神经计算，包括：更新关于控制是否会被 下一刻需要，并决定是否值得尝试施加控制，付出代价高昂的认知努力。的 本R 01的总体目标是阐明这些认知控制计算如何在禁食期间波动。 以及BN中的进食状态，潜在地保持了紊乱的周期性。具体而言，拟议的研究 结合了功能性磁共振成像（fMRI）、计算建模和实时移动的 评估食物摄入是否异常损害额纹状体功能， BN中与控制相关的更新和工作量评估流程。我们建议，这些损害 进食状态下的过程和禁食状态下这些过程的相对改善使非进食状态持续存在， 控制暴饮暴食/腹泻发作与饮食限制交替进行。我们将比较行为和 在抑制控制期间，BN女性对组匹配的健康女性的神经反应 范式，以评估控制相关的预测更新（目标1），并在认知努力折扣范式 评估控制相关的努力价值（目标2）在两种状态：16小时的快速和标准化餐后。 目标3将使用多模态症状测量来检查状态特异性的主要效应和潜在的相互作用。 更新和评估基线和6个月时暴饮暴食、腹泻和限制严重程度的过程 随访该研究团队包括以BN为重点的研究，神经成像，计算 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 创新性地1）应用神经计算框架来检查未充分研究的子组件的作用 2）评估代谢状态（禁食、进食）对这些子成分的影响; 以及3）将实验室中这些子组件的动态与真实世界的、特定于国家的经验联系起来 和症状的变化。从这个项目的数据将查明改变元素的控制 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 (i.e.,禁食或进食）进行控制性干预。因此，这项研究将产生重要的数据，以告知迫切 需要，精确的针对性治疗暴饮暴食，清除和限制的周期。

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.