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.

项目概要/摘要。 我们每天所做的决定都是由我们内在的驱动力所驱动的，我们要接近回报， 惩罚结果这些驱动力在决策中产生冲突，既有奖励结果，也有惩罚结果（ “接近-回避冲突”，AAC）。每个人的奖励和惩罚的平衡驱动偏见， 接近或回避审计咨询委员会的某项决定。情感障碍的特征是这种 平衡，导致AAC决策中更多的回避。因此，至关重要的是要阐明神经 奖励和惩罚驱动的基础，以及它们的破坏如何在临床上构成 不平衡的行为然而，虽然神经影像学工作已经证实了一个相关的关系， 虽然杏仁核和前额叶皮层与人类的回避行为有关，但没有研究表明杏仁核与回避行为的直接关系。 电生理信号（即，非粗体）与人类AAC行为相关，也未证实其因果关系 对电路动态和输出行为影响。 目前工作的目标是阐明杏仁核的因果作用，在接近和回避驱动 行为，以及前额叶皮层与这种关系的功能相关性。主要假设为 杏仁核会通过与前额叶皮层的连接主动地驱动回避。的 本研究的目的有三：1）绘制杏仁核的电生理图， 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 通过直接刺激杏仁核来抑制它; 3）为了阐明前额叶皮层的激活， 与杏仁核的操作，作为AAC行为的功能，通过记录高密度皮层 脑电图（hdEEG）与iEEG同步。AAC行为将使用一种新的， 评估接近-回避冲突驱动的有效任务。所有电生理记录和 将在任务期间提供刺激。杏仁核信号将主要量化为高伽马 用iEEG记录功率信号。前额叶皮质信号将主要量化为θ波段功率 用HDEEG记录。杏仁核和前额叶皮层之间的连接将通过 θ-γ耦合度量。 这一提议是创新的，因为它利用了尖端认知神经科学方法的整合， 描述人类的神经信号驱动回避行为。不管结果如何，这项研究 将在该领域产生新的问题，并提供一个严格的基准，据以开展进一步的工作， 外地从拟议的工作结果将提供关键信息领域的神经 在情感障碍中的驾驶回避行为学。