Testing a Memory-Based Hypothesis for Anhedonia

测试基于记忆的快感缺失假设

基本信息

批准号：
10598974
负责人：
JULIAN F. THAYER
金额：
$ 76.3万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-01-01 至 2027-10-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10598974
关键词：
Adult Age Years Algorithms Anhedonia Artificial Intelligence Behavior Behavioral Biological Biological Markers Brain Clinical Communities Computational Technique Computer Models Coupling Data Decision Making Diagnosis Diagnostic Diffusion Dimensions Disease Economic Burden Episodic memory Female Functional Magnetic Resonance Imaging Functional disorder Goals Health Care Costs Hippocampus Impairment Individual Intervention Knowledge Learning Libraries Link Magnetic Resonance Imaging Major Depressive Disorder Maps Measurement Measures Mediating Memory Mental Depression Mental disorders National Institute of Mental Health Neurobiology Neurosciences Outcome Patient Selection Patient Self-Report Pattern Positive Valence Post-Traumatic Stress Disorders Prevention Probability Process Psychiatry Psychological reinforcement Psychophysiology Public Health Quality of life Regulation Research Research Domain Criteria Resistance Resolution Rest Rewards Risk Sampling Schizophrenia Severities Signal Transduction Stimulus Structure Symptoms Techniques Testing Time Unemployment Ventral Striatum biomarker validation brain based candidate marker clinical decision-making clinical practice cognitive system cognitive task experience flexibility gray matter heart rate variability imaging modality improved innovation mathematical model memory process multimodality neurobiological mechanism neuroimaging neuromechanism novel pharmacologic pleasure predictive marker preservation rapid growth recruit reward circuitry reward processing suicidal risk therapy resistant tool treatment response white matter

项目摘要

PROJECT SUMMARY Anhedonia—the diminished capacity to experience pleasure from normally pleasurable stimuli—is a transdiagnostic symptom of multiple psychiatric disorders, including depression, schizophrenia and post- traumatic stress disorder. The recent and rapid growth of anhedonia research is fueled by its alarming clinical presentation: anhedonia is independently associated with increased risk of suicide, treatment resistance, and reduced quality of life. Major depressive disorder and schizophrenia—disorders of which anhedonia is a cardinal symptom—are linked with increasingly high levels of economic burden related to substantial health care costs and unemployment. There is currently no clear biological definition of anhedonia. As a result, clinicians rely on self-report measures with no clear established connection to its underlying neurobiology. While behavioral reward processing deficits and dysfunctional reward circuitry have been observed in anhedonia, in-the-moment reward responding is frequently preserved, suggesting that memory for the value of the experience may be compromised. This prompts the central question of this proposal: to what extent is anhedonia a memory problem? We propose to test a memory-based account for anhedonia as part of our goal to biologically define the construct. We note that while it is unlikely that memory is the only basis for anhedonia (certainly there are clear experiential aspects), it may be an understudied and underappreciated player. Critically, a well-defined memory contribution can help identify novel treatment targets and pave the path to improving clinical practice with biologically informed decision-making. We use a computational psychiatry approach, combining mathematical modeling of behavior in novel paradigms with advanced neuroimaging and AI tools to identify and validate biomarkers relevant to the prevention and treatment of anhedonia. We unite computational models of value, reinforcement learning, and episodic memory, bridging across the RDoC domains of Positive Valence and Cognitive Systems. Our aims are to: (1) Test the impact of anhedonia on value-modulated episodic memory and its neural mechanisms using high-resolution whole brain fMRI; (2) Test the impact of anhedonia on memory- guided decisions for reward and the associated neural mechanisms using high-resolution whole brain fMRI; and (3) Test the impact of anhedonia on structural and functional connectivity measures as well as autonomic regulation. We will also use AI/ML tools to create a multimodal library of predictive biomarkers for anhedonia. Our ultimate goal is to develop a comprehensive, mechanistic, and actionable memory-based account for anhedonia using new paradigms, computational models, high-resolution neuroimaging, as well as artificial intelligence approaches to develop novel interventions and improve clinical practice.

项目概要快感缺失——从通常令人愉悦的刺激中体验快乐的能力减弱——是一种多种精神疾病的跨诊断症状，包括抑郁症、精神分裂症和后遗症创伤性应激障碍的令人震惊的临床症状推动了快感缺失研究的快速增长。介绍：快感缺乏与自杀、治疗抵抗和自杀风险增加独立相关。生活质量下降。重度抑郁症和精神分裂症是其中最主要的疾病。症状——与巨额医疗费用相关的日益沉重的经济负担有关和失业目前还没有明确的生物学定义。自我报告的措施与其潜在的神经生物学没有明确的联系。在快感缺失中观察到奖励处理缺陷和功能失调的奖励电路奖励反应经常被保留，这表明对经验价值的记忆可能会被保留。这就提出了该提案的核心问题：快感缺乏在多大程度上是一种记忆。问题是什么？我们建议测试基于记忆的快感缺失解释，作为我们生物学定义目标的一部分我们注意到，虽然记忆不太可能是快感缺失的唯一基础（当然也有）。明确的经验方面），它可能是一个未被充分研究和低估的玩家，重要的是，它是一个定义明确的玩家。记忆贡献可以帮助确定新的治疗目标并为改善临床实践铺平道路我们使用计算精神病学方法，结合生物学决策。使用先进的神经影像和人工智能工具对新颖范式中的行为进行数学建模，以识别和识别验证与快感缺失的预防和治疗相关的生物标志物我们统一了计算模型。值、强化学习和情景记忆，跨越正价和情景记忆的 RDoC 领域认知系统。我们的目标是：（1）测试快感缺乏对价值调节情景记忆和使用高分辨率全脑功能磁共振成像（fMRI）研究其神经机制；（2）测试快感缺乏对记忆的影响- 使用高分辨率全脑功能磁共振成像指导奖励决策和相关神经机制； (3) 测试快感缺乏对结构和功能连接测量以及自主神经的影响我们还将使用人工智能/机器学习工具创建快感缺失预测生物标志物的多模式库。我们的最终目标是开发一个全面的、机械的、可操作的、基于记忆的账户使用新范式、计算模型、高分辨率神经影像以及人工开发新干预措施和改善临床实践的情报方法。