Dynamic Neural Computations Underlying Cognitive Control in Bulimia Nervosa

项目摘要/摘要 神经性暴食症(BN)是一种致残性和慢性进食障碍，与医疗并发症和 过早死亡。迫切需要确定维持BN的机制，这可能会起到 新疗法的目标。大多数研究都假设BN是由稳定的、类似特征的因素持续存在的， 包括自我报告的冲动和施加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是间歇性的，并倾向于交替出现 限制进食或甚至禁食的时期，暗示着控制的间歇性振荡。此外，新兴市场 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 控制依赖于大量的神经计算，包括：更新关于控制是否将被 在下一个时刻需要，并决定是否值得付出昂贵的认知努力施加控制。这个 本R01的首要目标是阐明这些认知控制计算如何在FAST中波动 和BN的联邦州，潜在地保持了这种混乱的周期性。具体而言，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 评估食物摄入是否异常损害额纹状体功能和相关 国阵中与控制相关的更新和努力评估过程。我们建议，这些功能的损害 处于FED状态的进程和处于禁食状态的这些进程的相对改进保持不在 控制暴饮暴食和节制饮食的交替发作。我们将比较行为和 BN妇女在抑制性对照中对健康妇女的神经反应 评估与控制相关的预测更新的范式(目标1)和在认知努力期间的贴现范式 在两种状态下评估与控制相关的努力评估(目标2)：禁食16小时后和标准餐后。 目标3将使用多模式症状测量来检查特定状态的主要影响和潜在的交互作用 在基线和6个月内更新和评估暴饮暴食、排泄和限制严重程度的流程 后续行动。研究团队包括以国阵为重点的研究、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。该项目 创新性地1)应用神经计算框架来检查未被研究的子组件的作用 2)评估代谢状态(空腹、进食)对这些亚成分的影响； 3)将实验室中这些子组件的动态与真实世界、特定国家的经验联系起来 以及基线和一段时间内的症状。此项目中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 (即禁食或喂食)以控制为重点的干预措施。因此，这项研究将产生重要的数据，以供紧急通知 对于暴饮暴食、排泄和节制的循环，需要进行精确的针对性治疗。

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.