Brain Reward-Pathway Function and Neurocomputational Modeling in Anorexia Nervosa

描述（由申请人提供）：这个指导病人导向的研究职业发展（K23）奖的总体目标是1。2.为申请人提供在饮食失调，特别是神经性厌食症（RAN）方面进行独立功能磁共振脑成像（fMRI）研究的技能。2 .训练申请人使用新颖的神经计算建模方法，将心理学理论与潜在的神经基质联系起来；扩展我们在RAN中与食物和非食物（金钱）奖励处理相关的大脑活动的知识。1 .a。目的是研究腹侧纹状体奖赏通路的功能，使用功能磁共振成像和预期和意外的甜味刺激传递范式（O'Doherty et al . 2003）。我们假设，与对照组相比，从RAN和III期恢复的女性将减少腹侧纹状体的激活。在目标1.b。，利用fMRI数据的奖励条件反射计算模型，我们预计与对照组相比，III区的奖励学习信号减少，前腹侧纹状体的RAN恢复。目标2.。是为了研究在即时金钱奖励的刺激下，眼额叶皮层和纹状体的激活是否比连续神经刺激下的眶额叶皮层和纹状体激活减少（Tanaka et al . 2004）。相反，我们预计在延迟货币奖励期间，III和恢复的RAN在背外侧前额叶和顶叶皮层比对照组有更大的激活（Tanaka etal . 2004）。在目标2.b。，利用对获得的大脑数据的计算模型，我们预计与对照组相比，III和恢复的RAN减少了前腹侧纹状体的即时处理，但增加了背侧纹状体的延迟奖励处理。本研究采用了新颖的技术和范式。这将极大地推动饮食失调研究领域的发展，同时也是为申请人提供功能磁共振成像和神经计算建模培训的绝佳机会。申请人将接受饮食失调、fMRI脑成像和神经计算建模领域的知名专家的指导，并参加科罗拉多大学认知科学与心理学专业的课程。神经性厌食症是所有精神疾病中死亡率最高的。这一应用将有助于识别限制性AN型奖赏系统的干扰途径，为认识该病的发病机制提供新的思路，并为开发先进的治疗方法提供新的信息。

DESCRIPTION (provided by applicant): The overall goal of this Mentored Patient-Oriented Research Career Development (K23) Award is to 1. Provide the applicant with the skills to perform independent functional magnetic resonance brain imaging (fMRI) research in Eating Disorders, specifically Restricting Type Anorexia Nervosa (RAN), 2. Train the applicant in novel Neurocomputational Modeling approaches that link psychological theory with underlying neural substrates, and 3. Extend our knowledge on brain activity in RAN in relation to food and non-food (monetary) reward processing. Aim 1 .a. is to investigate the functionality of anteroventral striatum reward pathways using fMRI and a paradigm of expected and unexpected delivery of sweet taste stimuli (O'Doherty et al 2003). We hypothesize that women Recovered from and III with RAN will have reduced anteroventral striatum activation compared to control women. In Aim 1.b., using computational models for reward conditioning on the fMRI data, we expect reduced reward learning signals in III and Recovered RAN in the anteroventral striatum compared to controls. Aim 2.a. is to investigate if reduced orbitofrontal cortex and striatum activation compared to CW exists in III and Recovered RAN in response to monetary immediate reward (Tanaka et al 2004). In contrast we expect III and recovered RAN to have greater activation than controls in the dorsolateral prefrontal and parietal cortex during delayed monetary reward (Tanaka et al 2004). In Aim 2.b., using computational models on the acquired brain data, we expect in III and Recovered RAN reduced anteroventral striatum immediate, but increased dorsal striatum delayed reward processing compared to controls. This study uses novel technologies and paradigms. It will both advance the field of Eating Disorders research greatly as well as will be an excellent opportunity to provide the applicant with training in fMRI and Neurocomputational Modeling. The applicant will be mentored by renowned experts in the field of Eating Disorders, fMRI Brain Imaging and Neurocomputational Modeling, and he will attend courses in the Cognitive Science and Psychology Program at the University of Colorado. Anorexia Nervosa has the highest mortality among all psychiatric disorders. This application will help identify pathways of disturbance of the reward system in Restricting type AN, will provide new insight into the disease mechanism, and will provide us with new information for the development of advanced treatments.