The Computational Role of Corticostriatal Circuits in Binge-Eating Disorder Symptoms and Severity

皮质纹状体回路在暴食症症状和严重程度中的计算作用

• 批准号: 10593579
• 负责人: Laura A. Berner
• 金额: $ 25.35万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10593579
• 关键词: Adult; Age; American; Anorexia Nervosa; Behavior; Behavior Control; Behavior Disorders; Behavioral; Binge Eating; Binge eating disorder; Body mass index; Brain; Bulimia; COVID-19; Characteristics; Chronic Disease; Clinical; Cognitive; Cognitive deficits; Computer Models; Corpus striatum structure; Data; Decision Making; Diagnosis; Diagnostic; Disease; Distress; Dopamine; Dorsal; Eating Behavior; Eating Disorders; Environment; Exanthema; Exposure to; Feedback; Food; Frequencies; Functional Magnetic Resonance Imaging; Future; Goals; Health; Heterogeneity; Human; Hyperphagia; Impairment; Impulsivity; Individual; Interruption; Intervention; Knowledge; Learning; Link; Matched Group; Measures; Medical; Modeling; Morbidity - disease rate; Neurobiology; Neurotransmitters; Outcome; Patient Self-Report; Patients; Pattern; Persons; Phase; Pilot Projects; Process; Recurrence; Reporting; Research; Response to stimulus physiology; Role; Sensory; Severities; Stimulus; Symptoms; System; Testing; Theoretical model; Work; anorexia nervosa binge-purge subtype; brain based; causal model; disability; eating pathology; efficacious intervention; experience; goal oriented behavior; high reward; indexing; neural; neural circuit; neural model; neuromechanism; novel; pre-clinical research; predictive modeling; psychologic; reinforced behavior; response; sex; simulation; suicidal; theories; treatment response

PROJECT SUMMARY/ABSTRACT Binge-eating disorder (BED) is more common than any other eating disorder in the US and is associated with high rates of medical morbidity, disability, and suicidality. As roughly half of patients with BED remain symptomatic after current first-line treatments, there is a critical need to identify brain-based factors that perpetuate BED symptoms and that may serve as mechanistic targets for novel treatments. Current theoretical models posit that the recurrent, distressing, and out-of-control overeating that characterizes BED arises after a transition from ventral to dorsal corticostriatal circuit control over decision-making, and a corresponding shift from goal-oriented to habitual behavior. However, individuals with BED present with a co-occurrence of seemingly contradictory decision-making problems—impulsivity and perseveration—and a wide range of binge-eating severity. Neurobiological research to date has failed to account for this within-person combination of cognitive deficits or this between-person variability in symptoms. The goal of this R21 project is to test a neurocomputational model of BED that provides a more comprehensive account of symptoms and severity. This model expands on previous theories and links behavior to effective connectivity in corticostriatal circuits underlying decision-making. Specifically, the proposed study combines computational modeling of behavior with dynamic causal modeling (DCM) of neural connectivity to examine whether aberrant within- and between- circuit dynamics relate to cognitive and clinical symptom profiles in BED. We will compare effective connectivity of 28 adults with BED to that of 28 group-matched healthy controls during two decision-making paradigms. We will test two overarching predictions that are informed by our simulations of corticostriatal circuit dynamics and associated behavior: 1) In individuals with BED, aberrant within-circuit dynamics, specifically overstability (high “gain”) within dorsal and ventral corticostriatal circuits, result in overweighting of initial evidence (leading to impulsivity) and promote choice selections that are insensitive to changes in the environment (perseveration); 2) In individuals with BED, aberrant between-circuit dynamics, specifically an over-influence of one corticostriatal circuit on the other (dorsal on ventral or vice-versa), promote more severe binge eating. These model predictions can explain the impulsive, out-of-control initiation of binge eating, why individuals with BED continue to binge eat despite fullness and distress (i.e., perseverate), and why some individuals with BED are more likely than others to more frequently initiate binge eating episodes. As such, data from this proof-of- concept pilot study will substantiate a novel neurocomputational model of BED symptoms and characterize alterations in neural circuit dynamics, not just neural activation, in BED. In addition, the data will support a future R01 application focused on testing the model among a wider diagnostic spectrum of individuals who binge eat. This work can ultimately inform new interventions with circuit-based targets to more effectively interrupt entrenched patterns of binge eating.

项目概要/摘要 在美国，暴食症 (BED) 比任何其他饮食失调症都更常见，并且与 大约一半的暴食症患者仍然存在较高的医疗发病率、残疾率和自杀率。 目前的一线治疗后出现症状，迫切需要确定基于大脑的因素 使暴食症症状长期存在，这可能作为当前理论治疗的机制目标。 模型认为，反复出现的、令人痛苦的、失控的暴饮暴食是暴饮暴食的特征，这种暴饮暴食是在暴饮暴食之后出现的。 从腹侧到背侧皮质纹状体回路对决策的控制的转变，以及相应的转变 然而，患有暴食症的人会同时出现以下行为。 看似矛盾的决策问题——冲动和坚持——以及各种各样的问题 迄今为止，神经生物学研究未能解释这种人体内的组合。 R21 项目的目标是测试认知缺陷或症状的人与人之间的差异。 BED 的神经计算模型可以更全面地描述症状和严重程度。 该模型扩展了先前的理论，并将行为与皮质纹状体回路的有效连接联系起来 具体来说，拟议的研究结合了行为的计算模型。 使用神经连接的动态因果模型（DCM）来检查内部和之间是否存在异常 电路动力学与 BED 中的认知和临床症状特征相关，我们将比较有效的连接。 在两种决策范式中，将 28 名患有 BED 的成年人与 28 名分组匹配的健康对照者进行比较。 将测试两个总体预测，这些预测是通过我们对皮质纹状体电路动力学的模拟得出的 相关行为：1) 在患有暴食症的个体中，异常的电路内动态，特别是过度稳定（高 “增益”）在背侧和腹侧皮质纹状体回路中，导致初始证据的权重过大（导致 冲动）并促进对环境变化不敏感的选择（坚持）； 2) 在患有暴食症的个体中，回路间的动态异常，特别是某一回路的过度影响 另一侧的皮质纹状体回路（背侧位于腹侧，反之亦然），会促进更严重的暴饮暴食。 模型预测可以解释暴食症患者冲动、失控的暴食行为 尽管饱腹感和痛苦仍然继续暴饮暴食（即坚持），以及为什么一些患有暴食症的人 比其他人更有可能更频繁地引发暴食事件，因此，来自此证明的数据- 概念试点研究将证实一种新的暴食症状神经计算模型并表征 BED 中神经回路动力学的改变，而不仅仅是神经激活的改变。 未来的 R01 应用程序侧重于在更广泛的诊断范围内测试模型 这项工作最终可以为基于回路的目标提供新的干预措施，从而更有效地进行。 打破根深蒂固的暴饮暴食模式。