Identifying the causal role of the amygdala in human approach-avoidance conflict behavior test

确定杏仁核在人类接近-回避冲突行为测试中的因果作用

• 批准号: 10516014
• 负责人: Camarin Rolle
• 金额: $ 6.97万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10516014
• 关键词: Address; Affective; Amygdaloid structure; Animals; Attenuated; Automobile Driving; Behavior; Benchmarking; Bilateral; Blood; Bolus Infusion; Clinical; Conflict (Psychology); Coupling; Decision Making; Devices; Electroencephalogram; Electroencephalography; Electrophysiology (science); Epilepsy; Equilibrium; Etiology; Generalized Anxiety Disorder; Goals; Human; Individual; Intrinsic drive; Juice; Knowledge; Lead; Learning; Lesion; Major Depressive Disorder; Maps; Methods; Mission; Modeling; Mood Disorders; Occupational; Occupations; Oral; Outcome; Outcome Study; Output; Oxygen; Participant; Play; Post-Traumatic Stress Disorders; Prefrontal Cortex; Primates; Public Health; Punishment; Research; Resolution; Rewards; Role; Shock; Signal Transduction; Synaptic Membranes; Testing; United States National Institutes of Health; Wages; Work; Workload; approach avoidance behavior; approach behavior; avoidance behavior; behavior influence; behavior test; cognitive neuroscience; density; disability; implantation; indexing; innovation; neuroimaging; neurotransmission; novel; novel strategies; operation; primary outcome; relating to nervous system; social; symptomatology; targeted biomarker; targeted treatment

Project Summary/Abstract. The decisions we make day-to-day are motivated by our intrinsic drives to approach rewarding, and avoid punishing, outcomes. These drives conflict in decisions with both rewarding and punishing outcomes (termed “approach-avoidance conflict”, AAC). Each individual’s balance of reward- and punishment- drives bias the approach or avoidance of a given AAC decision. Affective disorders are characterized by a disruption in this balance, causing greater avoidance in AAC decisions. Therefore, it is critically important to elucidate the neural substrates underlying reward- and punishment- drives, and how their disruption constitutes clinically imbalanced behavior. However, while neuroimaging work has corroborated a correlational relationship of the amygdala and prefrontal cortex to avoidant behavior in humans, no study has mapped the amygdala’s direct electrophysiological signals (i.e., non-BOLD) relevant to AAC behavior in humans, nor substantiated its causal influence on circuit dynamics and output behavior. The goal of the current work is to elucidate the amygdala’s causal role in approach- and avoidance-driven behavior, and the functional relevance of the prefrontal cortex to this relationship. The primary hypothesis is that the amygdala will actively drive avoidance through its connectivity with the prefrontal cortex. The hypothesis will be tested with three primary aims: 1) To map amygdala electrophysiology relevant to behavior during AAC using invasive amygdala recordings (iEEG) 2) To examine the causal role of the amygdala in AAC by inhibiting it using direct amygdala stimulation and 3) To elucidate the prefrontal cortical activation, in operation with the amygdala, as a function of AAC behavior by recording high-density cortical electroencephalogram (hdEEG) simultaneous to iEEG. AAC behavior will be quantified using a novel, validated task assessing approach-avoidance conflict drives. All electrophysiological recordings and stimulation will be delivered during the task. Amygdala signal will be primarily quantified as the high gamma power signal recorded with iEEG. Prefrontal cortical signal will be primarily quantified as the theta-band power recorded with hdEEG. Connectivity between the amygdala and prefrontal cortex will be quantified through theta-gamma coupling metrics. This proposal is innovative as it leverages the integration of cutting-edge cognitive neuroscience methods to characterize the neural signal driving avoidance behavior in humans. Regardless of the outcomes, the study will generate new questions in the field, and provide a rigorous benchmark against which to hold further work in the field. Findings from the proposed work will provide critical information to the field regarding the neural features driving avoidance symptomatology in affective disorders.

项目摘要/摘要。 我们日常做出的决定是由我们的内在驱动器动机来取得奖励的动机，并避免 惩罚，结果。这些在有奖励和惩罚结果（称为）的决策中引发了冲突 “避免进场冲突”，AAC）。每个人的奖励和惩罚之间的平衡 - 驱使偏见 方法或避免给定的AAC决定。情感障碍的特征是中断 平衡，在AAC决策中导致更大的回避。因此，阐明中性非常重要 奖励和惩罚 - 驱动器的基板以及它们的干扰如何临床构成 行为不平衡。但是，尽管神经影像学的工作证实了 杏仁核和前额叶皮层是人类回避行为的，没有研究绘制了杏仁核的直接 与人类的AAC行为相关的电生理信号（即非折叠），也没有证实其因果关系 对电路动力学和输出行为的影响。 当前工作的目的是阐明杏仁核在进场和避免驱动的因果关系 行为，以及前额叶皮层与这种关系的功能相关性。主要假设是 杏仁核将通过其与前额叶皮层的连通性积极避免回避。这 假设将以三个主要目的进行检验：1）绘制与行为相关的杏仁核电生理学 在AAC期间，使用侵入性杏仁核记录（IEEG）2）检查杏仁核在AAC中的因果作用 通过使用直接杏仁核刺激抑制它，3）阐明前额叶皮质激活，在 通过记录高密度皮质的AAC行为的函数，使用杏仁核操作 脑电图（HDEEG）与IEEG同时。 AAC行为将使用小说进行量化 经过验证的任务评估方法避免冲突驱动器。所有电生理记录和 任务期间将传递刺激。杏仁核信号将被主要量化为高γ 电源信号与IEEG记录。前额叶皮质信号将被原始量化为theta波段功率 与Hdeeg一起录制。杏仁核和前额叶皮层之间的连通性将通过 theta-gamma耦合指标。 该建议具有创新性，因为它利用了尖端的认知神经科学方法的整合到 表征人类驱动避免行为的神经信号。无论结果如何 将在该领域产生新问题，并提供严格的基准，以进行进一步的工作 领域。拟议工作中的发现将向现场提供有关中性的关键信息 在情感障碍中推动避免症状的特征。