Neural Mechanisms of Emotional Memory Modulation in Major Depression

重度抑郁症情绪记忆调节的神经机制

• 批准号: 9110330
• 负责人: Michael A Yassa
• 金额: $ 38.63万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-05 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9110330
• 关键词: Adult; Affect; Amygdaloid structure; Anterior; Anxiety; Behavioral; Biological Markers; Brain; Clinical; Code; Corpus striatum structure; Coupled; Depressed mood; Diagnosis; Diffusion; Diffusion Magnetic Resonance Imaging; Dimensions; Discrimination; Disease; Emotional; Emotions; Episodic memory; Exhibits; Face; Feeling suicidal; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Health; Hippocampus (Brain); Human; Image; Imaging Techniques; Individual; Intervention; Learning; Light; Link; Literature; Magnetic Resonance Imaging; Major Depressive Disorder; Medial; Memory; Memory impairment; Mental Depression; Mental disorders; Methods; Moods; Neurobiology; Nucleus Accumbens; Patients; Pattern; Perforant Pathway; Performance; Play; Population; Prefrontal Cortex; Prevalence; Process; Psychopathology; Public Health; Research Domain Criteria; Resolution; Rest; Role; Sampling; Science; Signal Transduction; Societies; Stimulus; Structure of terminal stria nuclei of preoptic region; Task Performances; Techniques; Testing; Ventral Tegmental Area; base; cognitive process; dentate gyrus; design; emotional stimulus; endophenotype; hemodynamics; imaging modality; improved; in vivo; innovation; neural correlate; neuroimaging; neuromechanism; novel; relating to nervous system; symptom cluster; trend

DESCRIPTION (provided by applicant): The goal of the proposed study is to investigate the neural mechanisms underlying the emotional modulation of hippocampal memory in healthy individuals and how alterations in the amygdala-hippocampal network contribute to the pathophysiology of Major Depressive Disorder (MDD). Major depressive disorder (MDD) is one of the most prevalent lifetime psychiatric disorders with a lifetime prevalence of 16.5%. It is characterized by a cluster of symptoms that range from depressed mood to suicidal ideation and persist for a period of over two weeks. Memory impairment is a core endophenotype of MDD and has been attributed to abnormalities in the hippocampus and amygdala, with both regions exhibiting changes in volume and functional activity. The hippocampus is generally believed to underlie our capacity for learning new declarative memories, while the amygdala is thought to play an important role in the emotional modulation of memories. The hippocampus (particularly the dentate gyrus and CA3 subfield) is critically involved in pattern separation, a computation by which similar or overlapping memories are orthogonalized using distinct neural codes, such that learning is possible despite the potential for interference. Pattern separation provides a robust empirical framework for testing hippocampal function by manipulating mnemonic interference. It can further be used as a platform for testing amygdala modulation of hippocampal memory if stimulus emotionality is included as a parameter. In addition to providing a better understanding of memory network dynamics in healthy brains, this framework can also be used to test hypotheses in depressed individuals and assess the functional integrity of various components of this network. To achieve these goals, we will use powerful high-resolution fMRI (1.5 mm isotropic) methods that are capable of dissociating subfield-specific signals, coupled with a parametric design manipulating interference and emotional content concurrently. We will use this design to examine emotional modulation of memory in the healthy brain, as well as abnormalities in these cognitive processes in MDD. We will also employ cutting-edge ultrahigh-resolution (<1mm) structural and diffusion imaging methods to better understand amygdala-hippocampal abnormalities in MDD. The proposed empirical framework for examining memory and emotion is highly innovative and the application to MDD has never been previously accomplished. Coupled with state-of-the-art neuroimaging techniques, this project will have a high impact on the science of learning, memory, and emotion as well as the neurobiological understanding of MDD. We use a Research Domain Criteria (RDoC) framework to investigate common pathophysiological mechanisms in depression and co-morbid anxiety, which will be assessed along continuous dimensions. Successful completion of this project will shed light on the neural basis of memory and emotional processing in the amygdala-hippocampal network and provide a better understanding of the network changes that occur in depression, paving the way to improving diagnosis and defining novel targets for intervention.

描述（由申请人提供）：拟议研究的目的是研究健康个体海马记忆情感调节的神经机制，以及杏仁核-海马网络的改变如何促进重度抑郁症（MDD）的病理生理学。重性抑郁障碍（MDD）是最常见的终身精神疾病之一，终生患病率为16.5%。其特征是一系列症状，从抑郁情绪到自杀念头，并持续两周以上。记忆障碍是MDD的核心内在表型，并且归因于海马和杏仁核的异常，这两个区域都表现出体积和功能活动的变化。海马体通常被认为是我们学习新的陈述性记忆的基础，而杏仁核被认为在记忆的情绪调节中起着重要作用。海马体（特别是齿状回和CA 3亚区）在模式分离中起着关键作用，模式分离是一种计算，通过这种计算，相似或重叠的记忆使用不同的神经代码进行正交化，因此尽管存在干扰的可能性，但学习是可能的。模式分离提供了一个强大的经验框架，通过操纵记忆干扰测试海马功能。如果将刺激的情绪性作为一个参数，它可以进一步用作测试海马记忆的杏仁核调制的平台。除了提供对健康大脑中记忆网络动态的更好理解外，该框架还可用于测试抑郁个体的假设，并评估该网络各个组成部分的功能完整性。为了实现这些目标，我们将使用功能强大的高分辨率fMRI（1.5 mm各向同性）方法，该方法能够分离子场特定信号，再加上同时操纵干扰和情感内容的参数化设计。我们将使用这个设计来检查健康大脑中记忆的情绪调节，以及MDD中这些认知过程的异常。我们还将采用最先进的超高分辨率（<1 mm）结构和弥散成像方法，以更好地了解MDD中的杏仁核-海马异常。所提出的经验框架，检查记忆和情绪是高度创新的应用MDD以前从未完成。再加上最先进的神经成像技术，该项目将对学习，记忆和情感科学以及MDD的神经生物学理解产生重大影响。我们使用研究领域标准（RDoC）的框架，以探讨共同的病理生理机制，抑郁症和共病焦虑，这将是评估沿着连续的维度。该项目的成功完成将揭示杏仁核-海马网络中记忆和情绪处理的神经基础，并更好地了解抑郁症中发生的网络变化，为改善诊断和定义新的干预目标铺平道路。