Computational mechanisms of memory disruption in depression

抑郁症记忆破坏的计算机制

• 批准号: 10515641
• 负责人: DANIEL G DILLON
• 金额: $ 41万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-12-01 至 2024-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10515641
• 关键词: Address; Adult; Affect; Amygdaloid structure; Anhedonia; Anxiety; Autobiography; Brain region; Chronic stress; Collection; Computer Models; Corpus striatum structure; Data; Decision Making; Depressed mood; Development; Diffusion; Dimensions; Disease; Electroencephalography; Emotional; Episodic memory; Event; Event-Related Potentials; Executive Dysfunction; Exposure to; Failure; Feeling hopeless; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Hippocampus; Impairment; Individual; Individual Differences; Investigation; Knowledge; Lead; Learning; Link; Literature; Major Depressive Disorder; Memory; Memory impairment; Mental Depression; Methodology; Modeling; Moods; Multimodal Imaging; Neurocognitive; Parietal; Parietal Lobe; Participant; Patients; Process; Public Health; Research; Retrieval; Rewards; Risk Factors; Severities; Signal Transduction; Source; Speed; Stimulus; Stress; Structure; Suicide; Symptoms; Testing; Time; Work; acute stress; chronic depression; clinically relevant; cost; depressive symptoms; design; disability; emotion dysregulation; executive function; imaging study; improved; innovation; insight; intraparietal sulcus; memory encoding; memory recognition; memory retrieval; multimodal neuroimaging; neural; response; stem; success

Relative to healthy adults, depressed individuals typically show excellent memory for negative material but poor memory for positive material. Furthermore, depression impairs recollection—the ability to retrieve vivid, contextual details about an event. These abnormalities trouble patients and appear to prolong depressive episodes, but they are not well understood. Therefore, this proposal will use multi-modal neuroimaging and computational modeling to investigate the encoding and retrieval of emotional memories in depressed adults. To investigate categorical effects of depression, electroencephalogram (EEG)/event-related potential (ERP) data will be collected from 64 unmedicated adults with MDD and 64 healthy controls (n = 128). To investigate dimensional effects of depression, functional magnetic resonance imaging (fMRI) data will be acquired from adults selected for minimal, mild, moderate, or severe depressive symptoms (n = 36). On Day 1, the participants will study negative and positive words in the context of two encoding tasks. On Day 2, they will return for a recognition memory test in which the “old” encoded words will be presented with similar “new” words. When a participant recognizes an old word, source memory (recollection) will be tested by asking which task the word was encoded with. Day 2 will include exposure to acute stress, to potentiate emotional biases. This comprehensive design will support three aims. Aim 1 will use EEG/ERP to test the hypothesis that MDD blunts cortical responses to positive vs. negative stimuli at encoding and retrieval. We expect ERPs linked to memory formation and retrieval to be reduced for positive material, but not negative material, in adults with MDD vs. controls. Moreover, we expect such effects to be exaggerated after stress exposure. Importantly, the EEG/ERP methodology cannot detect activity in subcortical brain regions important for memory, such as the amygdala. Therefore, Aim 2 will use fMRI to test the hypothesis that depressive severity correlates with activation in subcortical structures that support retrieval. We expect that as depressive severity increases, activation of the amygdala, hippocampus, and parietal cortex to negative memory probes will increase. By contrast, activation of the striatum, hippocampus, and parietal cortex to positive memory probes should decrease. Finally, to gain insight into the underlying mechanisms that support memory, Aim 3 will use the HDDM to reveal the impact of depression on decision-making at retrieval. The Hierarchical Drift Diffusion Model (HDDM) is a computational model that can estimate the evidence accumulation process that enables us to choose between two options (e.g., old vs. new). We predict that the speed of evidence accumulation—drift rate—will be reduced for positive, but not negative, memory probes in depressed adults. Moreover, increased depression is expected to weaken relationships between drift rate and EEG/fMRI signals that support memory for positive material, but it should strengthen such relationships for negative material. This combination of computational modeling and multi-modal imaging will yield new insight into memory deficits in depression.

相对于健康的成年人，抑郁的人通常对负面材料表现出极好的记忆力，但 对正片的记忆力很差。此外，抑郁症还会损害记忆--回忆生动、 有关事件的上下文详细信息。这些异常困扰着患者，似乎延长了抑郁的时间。 插曲，但它们并没有被很好地理解。因此，这项提议将使用多模式神经成像和 研究成人抑郁症患者情绪记忆编码和提取的计算模型。 研究抑郁症的分类效应、脑电(EEG)/事件相关电位 事件相关电位数据来自未服药的MDD成人和健康对照(n=128)。至 研究抑郁症的维度效应，功能磁共振成像(FMRI)数据将 获得者为轻度、轻度、中度或重度抑郁症状的成人(n=36)。在第一天， 受试者将在两个编码任务的背景下学习否定词和积极词。在第二天，他们将 返回以进行识别记忆测试，在该测试中，将向“旧”编码单词呈现类似的“新”单词。 字里行间。当参与者认出一个旧单词时，将通过询问哪一个来测试来源记忆(回忆) 对单词进行编码的任务。第二天将包括暴露在严重的压力下，以加强情感偏见。 这一综合设计将支持三个目标。目标1将使用脑电/事件相关电位来检验假设 MDD在编码和提取时使皮层对积极刺激和消极刺激的反应变得迟钝。我们预计ERPS 在成年人中，与记忆形成和提取有关的积极材料，而不是消极材料，是减少的 MDD与对照的对比。此外，我们预计这种影响在压力暴露后会被夸大。重要的是 EEG/ERP方法无法检测到皮层下对记忆重要的脑区的活动，例如 杏仁核。因此，目标2将使用功能磁共振成像来测试抑郁严重程度与 支持检索的皮质下结构中的激活。我们预计，随着抑郁严重程度的增加， 杏仁核、海马体和顶叶皮质对负性记忆探针的激活将增加。通过 相比之下，纹状体、海马体和顶叶皮质对阳性记忆探针的激活应该 减少。最后，为了深入了解支持内存的底层机制，Aim 3将使用 HDDM以揭示抑郁对提取时决策的影响。分层漂移扩散 模型(HDDM)是一种计算模型，它可以估计证据积累过程，使我们能够 在两个选项之间进行选择(例如，旧的和新的)。我们预测证据积累的速度-漂移 比率-抑郁症成年人的积极但不是消极的记忆探测将会降低。此外，增加了 抑郁被认为会削弱漂移率与支持记忆的脑电/功能磁共振信号之间的关系 对于积极的材料，但它应该加强这种关系对于消极的材料。这一组合 计算建模和多模式成像将为抑郁症的记忆缺陷提供新的见解。

项目成果

Fast evidence accumulation in social anxiety disorder enhances decision making in a probabilistic reward task.

社交焦虑症中的快速证据积累可以增强概率奖励任务中的决策。

• DOI: 10.1037/emo0001053
• 发表时间: 2022-02
• 期刊: EMOTION
• 影响因子: 4.2
• 作者: Dillon, Daniel G;Lazarov, Amit;Dolan, Sarah;Bar-Haim, Yair;Pizzagalli, Diego A;Schneier, Franklin R
• 通讯作者: Schneier, Franklin R

Altered coordination between frontal delta and parietal alpha networks underlies anhedonia and depressive rumination in major depressive disorder.

• DOI: 10.1503/jpn.220046
• 发表时间: 2022-11
• 期刊: JOURNAL OF PSYCHIATRY & NEUROSCIENCE
• 影响因子: 4.3
• 作者: Chao, Zenas C. C.;Dillon, Daniel G. G.;Liu, Yi-Hung;Barrick, Elyssa M. M.;Wu, Chien-Te
• 通讯作者: Wu, Chien-Te

Postnatal Phencyclidine-Induced Deficits in Decision Making Are Ameliorated by Optogenetic Inhibition of Ventromedial Orbitofrontal Cortical Glutamate Neurons.

• DOI: 10.1016/j.bpsgos.2023.08.002
• 发表时间: 2024-01
• 期刊: Biological psychiatry global open science