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

项目摘要 经典厌恶性条件反射是一个成熟的实验室模型，用于研究 防御性反应。在实验动物和人类中，迄今为止的研究主要集中在 关于边缘结构的作用（例如，杏仁核）在这些反应中。最近的证据表明 大脑的感觉和注意力控制系统在维持神经功能方面的重要贡献。 条件反应的表征，并促进其灭绝。拟议的研究打破了新 通过将新的神经成像技术与先进的计算方法相结合， 大脑的视觉和注意力过程是人类获得和消除恐惧的基础。重大进展 将围绕沿着三个具体目标展开。在目标1中，我们描述了视觉皮层的脑网络动力学特征， 威胁偏见的形成，消退，并在两天的学习范式回忆。在目标2中，我们建立并测试了 威胁偏见概括的计算模型。在目标3中，我们考察了个体之间的关系， 条件视皮层威胁偏见的概括和回忆的差异以及 对条件性威胁的自主神经反应性增强，这是一种评估易患 发展成恐惧和焦虑症预计实现这些研究目标将解决 两个NIMH战略优先事项：定义复杂行为背后的电路和大脑网络（目标 1)以及从对疾病的理解中识别和验证新的治疗靶点 机制（目标3）。进一步预计，这一项目将使研究范式的转变， 对威胁的注意力从主要集中在边缘-前额叶回路的注意力， 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.