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：
10189703
负责人：
MICHAEL W. SCHLUND
金额：
$ 31.2万
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 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10189703
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，影响更多女人比男人。长期避免外部威胁和负面思想/感觉是一种突出的诊断功能。但是，我们缺乏精神病或生物学测定方法来衡量或预测功能结果和指导治疗，以减少回避。因此，我们需要病因以理论和人类研究为基础的模型阐明了脆弱性的神经标记避免男人和女人，并有助于开发量身定制的，性别特定的干预措施。这应用程序借鉴了情感和决策神经科学，以解决激活如何相关的避免的决策在焦虑的个人与焦虑低的人之间有所不同。我们将现实世界社会方法避免（AP-AV）决策的行为模型与 fMRI测量社会奖励威胁价值差异和结果的信号。我们的模型提示背侧扣带回（DACC）和背侧前额叶皮层（DMPFC）信号方法和回避行动之间的价值差异，而腹侧前额叶 Cortex（VMPFC）信号奖励和威胁结果的价值。威胁前岛（AI）信号奖励相互作用的腹侧纹状体（VS）信号。初步数据表明个人具有高体验式回避基础选择，可以接近/避免进行明显改变的信号传导奖励威胁价值的差异和结果。这种有偏见的信号可以解释过多回避或暗示潜在的机制。我们提出了两个神经成像实验旨在确定改变的信号是否反映了焦虑中稳定的神经病理学疾病或行为治疗常见的威胁/奖励操纵是否可以标准化信号并增加进近行为。对于每个人，我们都将招募健康（25m/25f）和临床上的焦虑（25m/25f）18-35岁的成年人在年龄，性别，种族，SES和IQ上匹配（总n = 200）。我们旨在确定焦虑调节信号传导的程度和（1）降低威胁会增加进近行为，并使信号传导和连通性归一化；（2）增加奖励会增加进近行为，并使信号传导和连通性归一化；和（3）性别调节奖励威胁价值差异和结果的信号。我们的完成目标将对回避决策的神经机制产生详细的理解焦虑，对奖励威胁价值差异的反应和性别差异。