Neural markers of avoidant decision-making in anxiety disorders

焦虑症回避决策的神经标志物

基本信息

批准号：
10016374
负责人：
MICHAEL W. SCHLUND
金额：
$ 35.63万
依托单位：
GEORGIA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-11 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10016374
关键词：
Address Adult Affect Affective Age Aggressive behavior Anterior Anxiety Anxiety Disorders Avoidance Learning Behavior Therapy Behavioral Model Biological Assay Biological Markers Chronic Clinical Data Decision Making Development Diagnostic Dorsal Ethnic Origin Etiology Feeling Female Foundations Functional Magnetic Resonance Imaging Human Individual Insula of Reil Intervention Investigation Link Measures Medial Mental disorders Modeling National Institute of Mental Health Negative Valence Neurosciences Outcome Outcomes Research Participant Persons Positive Valence Prefrontal Cortex Research Research Domain Criteria Rewards Severities Sex Differences Signal Transduction Strategic Planning System Thinking United States Ventral Striatum Woman analog anxious anxious individuals approach behavior base design experimental study functional outcomes male men neural correlate neuroimaging neuromechanism neuropathology novel personalized medicine recruit relating to nervous system sex social theories

项目摘要

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.

抽象的焦虑症是美国最常见的精神疾病，影响更多人女性比男性。长期回避外部威胁和消极想法/感受是一种突出的诊断特征。然而，我们缺乏精神病学或生物学测定来测量或预测功能结果并指导减少回避的治疗。因此我们需要从病因学角度以理论和人类研究为基础的模型，用于阐明脆弱性的神经标记避免男性和女性，并帮助制定针对特定性别的量身定制的干预措施。这应用程序利用情感和决策神经科学来解决激活如何关联焦虑的人和低度焦虑的人在回避决策方面存在差异。我们将现实世界的社交回避（AP-AV）决策的行为模型与 fMRI 用于测量社会奖励-威胁价值差异和结果的信号。我们的模型表明背侧前扣带回 (dACC) 和背侧内侧前额叶皮层 (dmPFC) 信号重视接近和回避动作之间的差异，而腹内侧前额叶皮质（vmPFC）发出奖励和威胁结果的价值信号。前岛叶 (AI) 威胁信号和腹侧纹状体（VS）的奖励信号也相互作用。初步数据显示，个人具有高经验回避基础选择来接近/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回避或提出潜在的机制。我们提出两个神经影像实验旨在确定改变的信号传导是否反映了焦虑中稳定的神经病理学行为治疗中常见的威胁/奖励操纵是否可以使信号正常化并增加接近行为。对于每个我们都会招募健康的（25M/25F）和临床焦虑 (25M/25F) 18-35 岁成年人在年龄、性别、种族、SES 和 IQ 上相匹配（总数 N=200）。我们的目标是确定焦虑调节信号传导的程度以及（1）威胁减少会增加接近行为并使信号和连接正常化； (2) 奖励的增加会增加接近行为并使信号和连接正常化；和 (3)性别调节奖励-威胁价值差异和结果的信号。完成我们的目标将详细了解回避决策的神经机制焦虑、对奖励-威胁价值差异的反应以及性别差异。