Reward Systems and Food Avoidance in Adolescents with Low Weight Eating Disorders

项目摘要 低体重饮食障碍是一种严重的精神障碍，最常发生在青春期，有 慢性病程，且有证据显示治疗反应差。这些障碍的一个核心特征是避免进食； 可以在研究领域标准(RDoC)框架中将其概念化为 急性威胁(即，食物厌恶)和奖励学习(即，对 食物缺失)。新出现的神经影像证据表明，岛叶-杏仁核-腹侧纹状体的缺陷 (IAVS)神经回路有助于个体在厌恶学习和奖赏学习中的变异性，这些大脑 各地区对食物/进食刺激表现出异常反应。我们的试点数据表明，患有低血压病的患者 体重进食障碍(LW-ED)在颠倒学习中难以消除食物线索联系 与健康对照相比，这一困难与厌恶的心理生理测量有关。 厌恶(而不是恐惧)。此外，我们的数据表明，对避免食物或 可能会进一步损害食物-线索关联的逆转的“线索安全”，因为它阻止了对 威胁性刺激。为此，我们还成功地试行了内感暴露干预。 针对内脏敏感性并寻求增加对IAVS神经回路的自上而下调节的人群。 这种干预与现有的基于应急管理的行为干预是不同的 是这一群体的标准，并以食物和饮食的奖励价值为目标。更进一步，同时 从我们团队获得的fMRI-肌电(EMG)试验数据表明，厌恶-厌恶情绪上升 反应与脑岛和杏仁核之间的连通性增加有关，并且提示脑岛和杏仁核之间缺乏 食物奖励与杏仁核和腹侧纹状体之间的连接增加有关 快感反应提升。拟议的项目将(A)使用新的fMRI-EMG来测试这种关系 杏仁核-岛叶-腹侧纹状体网络内的有效连接及其与 60例青少年急性威胁和奖赏学习的心理生理和行为测量 EDS和30名健康对照，(B)测试该网络对实验性内感觉暴露的敏感性 使用动态因果关系接受基于家庭的体重恢复治疗的患者的范例 实验前fMRI-EMG数据的建模，(C)针对客观情况验证该模型 实验室和真实世界饮食行为的测量。这项研究的结果将有助于我们更好地理解 威胁处理和奖赏/厌恶学习的核心神经回路，以及这个回路是如何 与客观行为有关。此外，我们将通过两种不同的方法来确定这种神经回路的可修复性。 针对情感处理和奖赏学习的不同方面选择行为干预。这些 数据将被用来为未来的临床干预提供信息，目标是在该人群中进行厌恶/奖励学习 以及岛叶-杏仁核-腹侧纹状体亚回路的失调。

Project Summary Low weight eating disorders are severe psychiatric disorders that most often develop in adolescence, have a chronic course, and evidence poor response to treatment. A core feature of these disorders is food avoidance; which can be conceptualized in the research domain criteria (RDoC) framework as dysregulation in the dimensional expression of acute threat (i.e., food aversion) and reward learning (i.e., pleasurable response to food absence). Emerging neuroimaging evidence suggests that deficits in insula-amygdala-ventral striatum (IAVS) neurocircuitry contribute to individual variability in aversive and reward learning, and that these brain regions demonstrate abnormal responses to food/eating stimuli. Our pilot data suggest that patients with low weight eating disorder (LW-ED) experience difficulty extinguishing food-cue associations in a reversal learning paradigm compared to healthy controls, a difficulty that is related to psychophysiological measures of aversive- disgust (not fear). Additionally, our data indicate the presence of a pleasure response to food avoidance or ‘cued safety’ that may further impair reversal of food-cue associations because it prevents reappraisal of the threatening stimuli. We have also successfully piloted an interoceptive exposure intervention for this population that targets visceral sensitivity and seeks to increase ‘top-down’ regulation of the IAVS neurocircuit. This intervention is distinguishable from existing contingency management based behavioral interventions that are standard for this population and target the reward value of food and eating. Further, simultaneously acquired fMRI-electromyography(EMG) pilot data from our team suggests that an elevated aversive-disgust response is associated with increased connectivity between insula and amygdala, and the cued absence of the food reward is associated with elevated connectivity between amygdala and ventral striatum that is associated with elevated pleasure response. The proposed project will (a) use novel fMRI-EMG to test the relationship between effective connectivity within amygdala-insula-ventral striatum network and its relationship to psychophysiological and behavioral measures of acute threat and reward learning in 60 adolescents with LW- EDs and 30 healthy controls, (b) test the sensitivity of this network to an experimental interoceptive exposure paradigm relative to patients receiving family based therapy for weight restoration using dynamic causal modeling of fMRI-EMG data pre-post experimental conditions, (c) validate this model against objective measures of laboratory and real world eating behavior. The results of this study will help us better understand the core neurocircuitry that underlies both threat processing and reward/aversive learning and how this circuit relates to objective behavior. Further, we will determine the modifiability of this neurocircuitry via two distinct behavioral interventions chosen to target different aspects of affective processing and reward learning. These data will be used to inform future clinical interventions targeting aversive/reward learning within this population and dysregulation in insula-amygdala-ventral striatum subcircuits.