The Influences of Eating and Fasting on Inhibitory Control in Bulimia Nervosa: A Computational Neuroimaging Study

项目摘要/摘要 神经性暴食症(BN)是一种常见的慢性进食障碍，与高残疾和早产儿有关。 死亡。迫切需要确定使BN症状永久化的基于大脑的因素，这可能有助于 作为新疗法的机械靶标。大多数研究都集中在暴饮暴食和排便行为上。 在BN中，并将这些症状与抑制控制缺陷和额纹状体激活减少联系起来。 然而，患有BN的人通常在有问题的控制不足和过度控制的状态之间摇摆。 暴饮暴食和限制摄入/禁食。到目前为止，神经生物学研究未能解释这一点。 振荡性。这个以患者为导向的导师研究职业发展奖的目标是更好地 理解BN中这两种状态下抑制控制的计算基础。具体地说， 建议的研究将功能磁共振成像(FMRI)与动态贝叶斯建模相结合，以 检查进食和禁食是否异常地影响患有BN的女性的大脑准备和工作 抑制性控制。这项研究将比较30名患有BN的女性和30名女性的神经反应。 在禁食16小时和标准餐后，在抑制性控制范例中匹配对照组。这 良好控制的设计将检验以下假设：1)在BN中，额纹状体信号用于预期需要 为了抑制，贝叶斯预测误差信号和反应抑制期间的激活在 进食状态，并且在禁食状态下异常增强(目标1)；2)改变对进食状态的反应 失控的进食和排泄，而对禁食状态的改变反应会持续很长时间 限制两次暴饮暴食/大扫除(目标2)。来自该项目的数据将证实一个解释性模型 在BN症状中，准确指出BN中哪些抑制过程的成分发生了变化，并识别 哪种以控制为重点的干预措施可能最有效。这项工作最终将准确地告知目标 以及上下文相关的干预措施，可以更有效地中断暴饮暴食、大扫除和 限制。该研究还将成为概念和技能方面的指导和实践培训的工具 对候选人的下一步行动至关重要。具体地说，在资源丰富的环境中，拟议的培训将 在三个领域给予应聘者新的专业知识：1)重复测量神经成像方法和 相关分析，2)神经计算模型和计算精神病学，3)神经生物学 BN的进食障碍症状的全部谱系。本项目及培训工作的完成情况 Goals将启动候选人在饮食失调和翻译神经科学领域的独立职业生涯 为结合神经成像和复杂分析方法的高影响研究奠定基础 提高进食障碍诊疗水平。

PROJECT SUMMARY/ABSTRACT Bulimia nervosa (BN) is an often-chronic eating disorder associated with high rates of disability and premature death. There is a critical need to identify brain-based factors that perpetuate BN symptoms and that may serve as mechanistic targets for novel treatments. Most studies have focused on binge eating and purging behaviors in BN and have linked these symptoms to inhibitory control deficits and reduced frontostriatal activation. However, individuals with BN typically oscillate between states of problematic under- and over-control— excessive eating and restricted intake/fasting. Neurobiological research to date has failed to account for this oscillation. The goal of this mentored patient-oriented research career development award is to better understand the computational underpinnings of inhibitory control in these two states in BN. Specifically, the proposed study combines functional magnetic resonance imaging (fMRI) with dynamic Bayesian modeling to examine whether eating and fasting abnormally impact how the brains of women with BN prepare for and exert inhibitory control. This study will compare neural responses of 30 women with BN to those of 30 group- matched controls during an inhibitory control paradigm after a 16-h fast and after a standardized meal. This well-controlled design will test the following hypotheses: 1) In BN, frontostriatal signals for the expected need to inhibit, Bayesian prediction error signals, and activation during response inhibition are abnormally blunted in a fed state, and abnormally enhanced in a fasted state (Aim 1); 2) Altered response to the fed state promotes out-of-control eating and purging, whereas altered response to the fasted state perpetuates prolonged restriction between binge/purge episodes (Aim 2). Data from this project will substantiate an explanatory model of BN symptoms, pinpoint which components of the inhibition process are altered in BN, and identify states in which control-focused interventions may be most effective. This work ultimately will inform precisely targeted and context-dependent interventions that can more effectively interrupt the cycle of binge eating, purging, and restriction. The study will also serve as a vehicle for mentorship and hands-on training in concepts and skills critical to the candidate’s next steps. Specifically, within a resource-rich environment, the proposed training will give the candidate new expertise in three domains: 1) repeated-measures neuroimaging methods and associated analyses, 2) neurocomputational modeling and computational psychiatry, and 3) the neurobiology of the full spectrum of disordered eating symptomatology in BN. This project and the completion of training goals will launch the candidate’s independent career in the translational neuroscience of eating disorders and lay groundwork for high-impact studies that combine neuroimaging and sophisticated analytic approaches to improve eating disorder diagnosis and treatment.