Brain Reward-Pathway Function and Neurocomputational Modeling in Anorexia Nervosa

描述（由申请人提供）：这个指导患者为导向的研究职业发展（K23）奖的总体目标是1。为申请人提供技能，以执行独立的功能性磁共振脑成像（fMRI）研究饮食失调，特别是限制型神经性厌食症（RAN），2。培训申请人在新的神经计算建模方法，将心理学理论与潜在的神经基板，和3。扩展我们对RAN中与食物和非食物（货币）奖励处理有关的大脑活动的知识。目标1.a是使用fMRI和预期和意外的甜味刺激传递的范例来研究前腹侧纹状体奖励通路的功能（O'Doherty等人2003）。我们假设，与对照组相比，患有RAN和III的女性前腹侧纹状体激活减少。在目标1.b中，使用计算模型的奖励条件的功能磁共振成像数据，我们预计减少奖励学习信号在III和前腹侧纹状体的RAN相比，控制。目标2.a.研究III和正常RAN中是否存在对金钱立即奖励的反应，与CW相比，眶额皮质和纹状体激活减少（Tanaka et al 2004）。相比之下，我们预计III和恢复的RAN在延迟金钱奖励期间在背外侧前额叶和顶叶皮层中具有比对照更大的激活（Tanaka等人，2004）。在目标2.b中，通过对获得的大脑数据使用计算模型，我们预期与对照组相比，在III期和恢复期的RAN中，前腹侧纹状体立即减少，但背侧纹状体延迟奖励处理增加。这项研究使用了新的技术和范式。这将大大推进饮食失调研究领域，并将是一个很好的机会，为申请人提供功能磁共振成像和神经计算建模培训。申请人将由饮食失调，功能磁共振成像脑成像和神经计算建模领域的知名专家指导，他将参加科罗拉多大学的认知科学和心理学课程。神经性厌食症在所有精神疾病中死亡率最高。这一应用将有助于确定限制型AN中奖励系统的干扰途径，将为疾病机制提供新的见解，并将为我们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.