Neural markers of avoidant decision-making in anxiety disorders

摘要 焦虑症是美国最常见的精神疾病，影响更大 女人比男人多。长期避免外部威胁和负面想法/感觉是一种 突出的诊断特征。然而，我们缺乏精神或生物测试来衡量或预测。 功能结果和减少回避的指导治疗。因此我们需要病因学 以理论和人体研究为基础的模型，以澄清易感性的神经标志物 避免男性和女性，并帮助制定量身定制的、针对性别的干预措施。这 应用程序利用情感和决策神经科学来解决激活如何与 具有回避性决策的焦虑个体和低焦虑个体之间存在差异。我们 将现实世界社交接近-避免(AP-AV)决策的行为模型与 FMRI用于测量社会奖励-威胁值差异和结果的信号。我们的模特 暗示背侧前扣带回(DACC)和背侧内侧前额叶皮质(DmPFC)信号 接近和回避动作之间的价值差异，而腹内侧前额叶 大脑皮质(VmPFC)代表奖励和威胁结果的价值。前岛(AI)威胁信号 腹侧纹状体(VS)的奖赏信号也相互作用。初步数据显示，个人 高体验回避基础选择接近/避免明显改变的信号 奖励-威胁价值差异和结果。这种有偏见的信号可以解释过度 避免或提出潜在的机制。我们提出了两个神经成像实验 旨在确定信号变化是否反映了焦虑的稳定神经病理 行为治疗中常见的威胁/奖励操作是否可以 规范信号传递，增加接近行为。我们将为每个员工招聘健康员工(25M/25F) 临床焦虑(25M/25F)18-35岁的成年人，年龄、性别、种族、社会地位和智商相匹配 (总N=200)。我们的目标是确定焦虑在多大程度上调节信号和(1) 减少威胁会增加接近行为，并使信令和连接正常化；(2) 增加奖励会增加接近行为，并使信号和连接正常化；以及 (3)性别调节奖励-威胁价值差异和结果的信号传递。完成我们的 AIMS将使我们更详细地理解回避性决策的神经机制。 焦虑、对奖励-威胁值的反应差异以及性别差异。

ABSTRACT Anxiety disorders are the most common mental illness in the United States and affect more women than men. Chronic avoidance of external threats and negative thoughts/feelings is a prominent diagnostic feature. Yet, we lack psychiatric or biological assays to measure or predict functional outcomes and guide treatments for reducing avoidance. We thus need etiological models grounded in theory and human research to clarify neural markers of vulnerability to avoidance in men and women and aid development of tailored, sex-specific interventions. This application draws on affective and decision neuroscience to address how activation associated with avoidant decision-making differs between anxious individuals and those with low anxiety. We couple a behavioral model of real-world social approach-avoidance (AP-AV) decision-making with fMRI to measure signaling of social reward-threat value differences and outcomes. Our model suggests the dorsal anterior cingulate (dACC) and dorsal medial prefrontal cortex (dmPFC) signal value differences between approach and avoidance actions, while the ventromedial prefrontal cortex (vmPFC) signals value of reward and threat outcomes. Anterior insula (AI) signals of threat and ventral striatum (VS) signals of reward also interplay. Preliminary data show that individuals with high experiential avoidance base choices to approach/avoid on distinctively altered signaling of reward-threat value differences and outcomes. Such biased signaling could explain excessive avoidance or suggest potential mechanisms. We propose two neuroimaging experiments designed to determine whether altered signaling reflects a stable neuropathology in anxiety disorders or whether threat/reward manipulations common to behavioral treatments can normalize signaling and increase approach behavior. For each we will recruit healthy (25M/25F) and clinically anxious (25M/25F) 18-35 yr-old adults matched on age, sex, ethnicity, SES, and IQ (total N=200). We aim to determine the extent to which anxiety modulates signaling and (1) decreased threat increases approach behavior and normalizes signaling and connectivity; (2) increased reward increases approach behavior and normalizes signaling and connectivity; and (3) sex modulates signaling of reward-threat value differences and outcomes. Completion of our aims will yield a detailed understanding of neural mechanisms of avoidant decision-making in anxiety, responsiveness to reward-threat value differences, and sex differences.