Evaluating State-Based Network Dynamics in Anhedonia

项目摘要/摘要 快感缺乏，即失去从事以前令人愉快的活动的动力，与显著的 临床损害。重要的是，快感缺乏与几种不同的精神疾病有关，呈现出一种 有希望的跨诊断治疗的机会。尽管有其临床意义，快感缺乏症通常是 作为主要治疗目标而被忽视。因此，开发有针对性的快感缺乏症治疗方法是 对人群心理健康至关重要。本提案旨在通过以下方式满足这一迫切需要 在跨诊断性快感缺乏症样本中澄清网络水平的神经功能障碍，长期目标是 确定潜在的治疗目标。具体地说，拟议的项目将采用图论方法。 解决以下具体目标：(1)建立大脑网络隔离和整合在 对奖励的预期预测无快感症状的严重程度，以及(2)评估网络中的变异性 当从休息转换到奖励预期时的重新配置有助于非享乐症状的严重程度。 建议的分析将利用已经从NIMH收集的基线神经成像和自我报告数据 合同(#HHSN271201200006I；PI：安德鲁·克里斯特尔，医学博士)。申请人的长期职业目标是从事 翻译研究使用新的翻译诊断方法来检查奖励的神经指数- 加工及其相关的临床意义与发展机械驱动的总体目标 治疗。因此，拟议的项目将提供有指导的培训，总体目标是深化 申请者的跨学科培训，弥合了临床心理学和认知神经科学之间的鸿沟。 具体的培训目标包括：(1)广泛培训先进的脑网络分析技术，以及图表- 理论方法，(2)加强对与快感缺乏症相关的循证临床研究的理解， (3)加强申请人的拨款撰写和提交技巧，以及建立她的出版纪录； 临床试验设计和管理方面的实用和应用培训，以及(5)关于伦理问题的进一步培训 心理学和负责任的研究行为。这一培训计划和研究建议已被 战略开发，以培养申请人作为研究人员的独立性，并为她配备专门的 跨学科的技能，为她作为一名翻译研究员的成功职业生涯做好准备。

PROJECT SUMMARY/ABSTRACT Anhedonia, the loss of motivation to engage in previously enjoyable activities, is associated with significant clinical impairment. Importantly, anhedonia is implicated in several different psychiatric disorders, presenting a promising opportunity for transdiagnostic treatment. In spite of its clinical significance, anhedonia is typically overlooked as a primary treatment target. Consequently, developing targeted treatments for anhedonia is of critical importance for population mental health. The present proposal aims to address this critical need by clarifying network-level neural dysfunction in a transdiagnostic anhedonia sample, with the long-term goal of identifying potential treatment targets. Specifically, the proposed project will take a graph-theoretical approach to address the following specific aims: (1) establish how brain network segregation and integration during the anticipation of rewards predict anhedonic symptom severity, and (2) assess how variability in network reconfiguration when transitioning from rest to reward anticipation contributes to anhedonic symptom severity. The proposed analyses will utilize already collected baseline neuroimaging and self-report data from a NIMH contract (#HHSN271201200006I; PI: Andrew Krystal, MD). The applicant’s long-term career goal is to conduct translational research utilizing novel, transdiagnostic methods to examine the neural indices of reward- processing and their associated clinical implications with the overall target of developing mechanistically driven treatments. As such, the proposed project will provide mentored training with the overall goal of deepening the applicant’s interdisciplinary training, bridging the gap between clinical psychology and cognitive neuroscience. Specific training goals include: (1) extensive training in advanced brain network analytic techniques, and graph- theoretical approaches, (2) enhanced understanding of evidence-based clinical research relevant to anhedonia, (3) bolstering the applicant’s grant-writing and presentation skills as well as building her publication record, (4) practical and applied training in clinical trial design and management, and (5) further training in ethical issues in psychology and the responsible conduct of research. This training plan and research proposal have been strategically developed to foster the applicant’s independence as a researcher and equip her with a specialized interdisciplinary skillset to prepare her for a successful career as a translational researcher.