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:
  • 金额:
    $ 76.3万
  • 依托单位:
  • 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

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.
项目摘要 快感缺失--从通常令人愉快的刺激中体验快乐的能力减弱--是一种 多种精神疾病的转诊症状,包括抑郁症、精神分裂症和精神分裂症后 创伤应激障碍快感缺乏症的研究最近迅速增长,其令人震惊的临床 介绍:快感缺失与自杀风险增加、治疗抵抗和 生活质量下降。重度抑郁症和精神分裂症-其中快感缺失是主要的障碍 与大量医疗保健费用有关的经济负担日益增加 和失业。目前对快感缺乏没有明确的生物学定义。因此,临床医生依赖于 自我报告的措施,没有明确的建立连接到其潜在的神经生物学。虽然行为 在快感缺乏症中,目前已经观察到奖励处理缺陷和功能失调的奖励回路, 奖励反应经常被保留下来,这表明对经验价值的记忆可能是 暴露了这就引出了这一提议的核心问题:快感缺失在多大程度上是一种记忆 有什么问题吗我们建议测试一个基于记忆的快感缺失解释,作为我们从生物学上定义快感缺失的目标的一部分。 结构。我们注意到,虽然记忆不太可能是快感缺失的唯一基础(当然有 明确的经验方面),它可能是一个研究不足和低估的球员。严格地说, 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 做出生物学上的决定。我们使用计算精神病学方法, 在新的范例中使用先进的神经成像和人工智能工具对行为进行数学建模, 验证与快感缺乏的预防和治疗相关的生物标志物。我们将计算模型 价值,强化学习和情景记忆,桥接正价和 认知系统。我们的目的是:(1)测试快感缺失对价值调节情景记忆的影响, 其神经机制使用高分辨率全脑功能磁共振成像;(2)测试快感缺失对记忆的影响- 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)测试快感缺失对结构和功能连接性指标以及自主神经功能的影响。 调控我们还将使用AI/ML工具创建一个用于快感缺乏的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帐户, 使用新的范例,计算模型,高分辨率神经成像,以及人工 智能方法开发新的干预措施和改善临床实践。

项目成果

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JULIAN F. THAYER其他文献

JULIAN F. THAYER的其他文献

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{{ truncateString('JULIAN F. THAYER', 18)}}的其他基金

DISTRESS AND ALCOHOL USE IN ETHNIC MINORITIES
少数民族的困境和酗酒
  • 批准号:
    3452675
  • 财政年份:
    1988
  • 资助金额:
    $ 76.3万
  • 项目类别:
DISTRESS AND ALCOHOL USE IN ETHNIC MINORITIES
少数民族的困境和酗酒
  • 批准号:
    3452673
  • 财政年份:
    1988
  • 资助金额:
    $ 76.3万
  • 项目类别:
DISTRESS AND ALCOHOL USE IN ETHNIC MINORITIES
少数民族的困境和酗酒
  • 批准号:
    3452674
  • 财政年份:
    1988
  • 资助金额:
    $ 76.3万
  • 项目类别:

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