Acquisition, extinction, and recall of attention biases to threat: Computational modeling and multimodal brain imaging

项目摘要 经典的厌恶条件反射是研究习得和消亡的一个成熟的实验室模型。 防御性反应。到目前为止，在实验动物和人类身上的研究主要集中在 边缘结构(如杏仁核)在这些反应中的作用。最近的证据开始强调 大脑的感觉和注意力控制系统在维持神经方面的重要贡献 条件性反应的表现和促进其消亡。这项拟议的研究具有突破性的意义 通过将新的神经成像技术与先进的计算方法相结合来检查 大脑的视觉和注意力过程是人类恐惧获得和消退的基础。重大进展 将沿着三个具体目标制定。在目标1中，我们描述了视觉皮质的脑网络动力学。 在两天的学习范式中，威胁偏向的形成、消失和回忆。在目标2中，我们建立并测试了一个 威胁偏向泛化的计算模型。在目标3中，我们考察了个体之间的关系 条件性视觉皮质威胁偏向的概化和回忆差异及个体差异 自主神经对条件性威胁的高度反应性，是评估易感性的潜在生物标志物 发展出恐惧和焦虑的障碍。预计实现这些研究目标将解决 NIMH的两个战略重点：定义复杂行为背后的电路和大脑网络(目标 1)确定和确认新的治疗目标，这些目标源于对疾病的了解 机制(目标3)。进一步预计，这一项目将使研究范式发生转变 对威胁的功能障碍的关注主要集中在边缘-前额叶回路，而不是 强调感觉、注意力、执行控制和边缘系统之间的相互作用。

Project Summary Classical aversive conditioning is a well-established laboratory model for studying acquisition and extinction of defensive responses. In experimental animals, as well as in humans, research to date has been mainly focused on the role of limbic structures (e.g., the amygdala) in these responses. Recent evidence has begun to stress the important contribution by the brain’s sensory and attention control systems in maintaining the neural representations of conditioned responses and in facilitating their extinction. The proposed research breaks new ground by combining novel neuroimaging techniques with advanced computational methods to examine the brain’s visual and attention processes underlying fear acquisition and extinction in humans. Major advances will be made along three specific aims. In Aim 1, we characterize the brain network dynamics of visuocortical threat bias formation, extinction, and recall in a two-day learning paradigm. In Aim 2, we establish and test a computational model of threat bias generalization. In Aim 3, we examine the relation between individual differences in generalization and recall of conditioned visuocortical threat biases and individual differences in heightened autonomic reactivity to conditioned threat, a potential biomarker for assessing the predisposition to developing the disorders of fear and anxiety. It is expected that accomplishing these research aims will address two NIMH strategic priorities: defining the circuitry and brain networks underlying complex behaviors (Objective 1) and identifying and validating new targets for treatment that are derived from the understanding of disease mechanisms (Objective 3). It is further expected that this project will enable a paradigm shift in research on dysfunctional attention to threat from one that focuses primarily on limbic-prefrontal circuits to one that emphasizes the interactions among sensory, attention, executive control and limbic systems.