Developing a computational electroencephalogram (EEG) paradigm to study prediction error in anorexia nervosa

摘要 青少年神经性厌食症（AN）是一种饮食失调症，与对体重增加、食物 拒绝和严重的体重下降。AN是青春期女性中第三大常见的慢性疾病， 15-24岁女性的死亡率比预期高12倍。对生物标志物知之甚少， 青少年AN.使用功能性磁共振成像（fMRI）等技术的神经成像研究 曾多次建议改变奖励处理AN，包括研究使用多巴胺相关的 预测误差（PE）模型。脑PE反应是在意外的接受或遗漏奖励时引起的 刺激和思想来反映大脑多巴胺回路的功能。这是一个重要的研究方向 因为多巴胺系统可以被随意操纵。患有AN的青少年或成人患者 显示出升高的PE反应，重复蔗糖味接收在纹状体和纹状体。PE也呈反比 与治疗中的体重增加有关。因此，PE脑反应有望成为一个重要的生物学标志物， 青少年AN治疗结果的预测价值。然而，功能性脑成像是昂贵的， 例如，对于身体中带有支架或其他金属的个人来说是禁止的，并且仅在某些 中心.为了在更大规模的研究中研究AN中的PE，需要更实用的方法和途径。 开发在本申请中，我们将使用探索性/开发性R21机制开展研究 使用脑电图（EEG）研究青少年AN的PE信号。最近的健康研究 个人支持这是一个有效的方法。 在目标1中。我们测试了适应计算品味PE强化学习范式的可行性， 青少年AN和健康对照组的fMRI和EEG。我们希望我们能找到内部一致性 味觉PE脑反应与扣带回和额叶脑电信号fMRI对比研究 AN青少年以及年龄匹配的健康对照的皮质区域。我们还希望， 找到初步证据表明，脑电图范式将能够区分AN组与对照组 青少年基于反馈相关的负性和更高的事件相关电位振幅。 在目标2中。我们测试了货币PE范式是否会显示出与味觉PE相似的EEG脑反应， 目标1.建立品味和非品味范式的普遍性。 基于EEG的奖励PE研究范式的发展将使我们能够在未来进行大规模的- 大规模的研究，将是成本较低，独立于大脑成像中心，只有提供给一个 一小群患有AN的青少年。

Abstract Adolescent anorexia nervosa (AN) is an eating disorder associated with intense fear of weight gain, food refusal, and severe weight loss. AN is the third most common chronic illness among adolescent females with a mortality rate 12 times higher than expected for females 15-24 years old. Little is known about biomarkers in adolescent AN. Neuroimaging studies using techniques such as functional magnetic resonance imaging (fMRI) have repeatedly suggested altered reward processing in AN including studies using the dopamine associated prediction error (PE) model. The brain PE response is elicited during unexpected receipt or omission of reward stimuli and thought to reflect the functionality of brain dopamine circuits. This is an important research direction as the dopamine system can be manipulated pharmacologically. Ill adolescent or adult individuals with AN showed elevated PE response to repeated sucrose taste receipt in insula and striatum. PE was also inversely related to weight gain in treatment. Thus, PE brain response promises to be an important biological marker for adolescent AN with predictive value for treatment outcome. However, functional brain imaging is costly, prohibitive for instance for individuals with braces or other metal in their body and only available at certain centers. In order to study PE in AN in larger scale studies, a more practical approach and method need to be developed. In this application, we will use the exploratory/developmental R21 mechanism to develop a study protocol using electroencephalography (EEG) to study PE signals in adolescent AN. Recent studies in healthy individuals support that this is a valid approach. In Aim 1. we test the feasibility of adapting a computational taste PE reinforcement learning paradigm from fMRI to EEG in adolescents with AN and healthy controls. We expect that we will find internal consistency of taste PE brain response between fMRI insula and striatum response and EEG signal in cingulate and frontal cortical regions in adolescents with AN as well as age-matched healthy controls. We further expect that we will find preliminary evidence that the EEG paradigm will be able to discriminate the AN group from the control adolescents based on feedback related negativity and higher event-related potential amplitudes. In Aim 2. we test whether a monetary PE paradigm will show similar EEG brain response as the taste PE in Aim 1. to establish the generalizability of taste and non-taste paradigms. The development of an EEG based reward PE study paradigm will enable us in the future to conduct large- scale studies that will be less costly and independent from brain imaging centers that are only available to a small subset of adolescents with AN.