Testing a Memory-Based Hypothesis for Anhedonia

测试基于记忆的快感缺失假设

• 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
• 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

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.

项目摘要 Anhedonia（从通常令人愉悦的刺激中体验愉悦的能力降低）是 多种精神疾病的转诊症状，包括抑郁症，精神分裂症和后 创伤性应激障碍。 Anhedonia研究的近期和快速增长源于其令人震惊的临床 演讲：Anhedonia独立于自杀，治疗耐药性和 减少生活质量。重度抑郁症和精神分裂症 - Anhedonia是红衣主教的疾病 症状 - 与越来越高的经济烧伤有关，与大量的医疗保健成本有关 和失业。目前尚无对阿尼奥尼亚的明确生物学定义。结果，临床医生依靠 自我报告措施没有与其基本神经生物学的明确联系。而行为 奖励处理缺陷和功能失调的奖励电路已在Anhedonia（矩）中观察到 经常保留奖励回应，表明对体验价值的记忆可能是 妥协。这提示了该提议的核心问题：Anhedonia在多大程度上是记忆 问题？我们建议测试对Anhedonia的基于内存的帐户，这是我们生物学定义的目标的一部分 结构。我们注意到，虽然记忆不太可能是Anhedonia的唯一基础（当然有） 明确的专家方面），这可能是一个被理解的和低估的球员。至关重要的是一个明确的 记忆贡献可以帮助识别新的治疗目标，并为改善临床实践铺平道路 带有知情的决策。我们使用计算精神病学方法，结合 具有高级神经影像学和AI工具的新型范式中行为的数学建模，以识别和 验证与预防和治疗Anhedonia有关的生物标志物。我们的单元计算模型的 价值，增强学习和情节记忆，跨越正价RDOC领域桥接 认知系统。我们的目的是：（1）测试Anhedonia对价值调节的情节记忆和 使用高分辨率的整个大脑fMRI的神经机制； （2）测试Anhedonia对记忆的影响 - 使用高分辨率的整个大脑fMRI的指导性决定和相关的神经机制；和 （3）测试Anhedonia对结构和功能连通性措施以及自主神经的影响 规定。我们还将使用AI/ML工具为Anhedonia创建多模式的预测生物标志物库。 我们的最终目标是为基于内存的全面，机械和可行的内存帐户开发 使用新范式，计算模型，高分辨率神经影像以及人造的Anhedonia 智力方法以开发新的干预措施并改善临床实践。