Neural Substrates of Anticipation and Interoception in Anxiety Disorders

描述(由申请人提供)：这项提案是我们正在进行的工作进入焦虑的神经基础的竞争性更新。在这项工作的自然进展中，我们现在建议测试焦虑症神经回路模型的关键方面。我们将结合情绪处理任务使用BOLD功能磁共振成像来比较健康对照受试者(HC)和惊恐障碍(PD)和广泛性焦虑症(GAD)患者，这些患者将在认知行为治疗(CBT)前后进行研究。这项建议汇集了行为和认知神经科学、功能神经成像和心理临床治疗学的方法和途径，概述了一系列研究，其长期目标是描绘焦虑症的神经基础。这一竞争性更新的主要目标是在申请者先前在有焦虑倾向的非临床个体上完成的工作的基础上，将其应用于焦虑症患者，具体目标如下：(1)开发焦虑症的基本系统神经科学内表型。基于我们之前的工作，我们假设，与健康对照组(HC)相比，GAD或PD患者在涉及内感系统的各种情绪处理过程中，前岛的激活会增加。此外，我们假设在焦虑症患者中，岛叶皮质与杏仁核和内侧前额叶皮质(MPFC)之间的功能耦合较少。(2)评价CBT对焦虑症患者假想神经系统功能障碍的影响。我们预计，成功的治疗将分别与岛叶皮质活动的减弱和岛叶与杏仁核和mPFC之间的耦合增加有关。在GAD的情况下，我们也预计会看到任务相关的背外侧前额叶皮质(DLPFC)活动减少。焦虑症是一种起病早、流行、严重的疾病，对个人和社会功能产生不利影响。对焦虑症神经回路的更好理解将为诊断概念化提供信息，并使基于对病理生理学更彻底了解的新疗法的开发和测试更具针对性，从而向许多现有治疗不足的焦虑症患者传达新的治疗选择。

DESCRIPTION (provided by applicant): This proposal is the competing renewal of our ongoing work into the neural substrates of anxiety. In a natural progression of this work, we now propose to test key aspects of a neural circuit model for anxiety disorders. We will use BOLD fMRI in conjunction with emotion processing tasks to compare healthy controls subjects (HC) to patients with panic disorder (PD) and generalized anxiety disorder (GAD), who will be studied before and after cognitive behavioral treatment (CBT). This proposal brings together methods and approaches from behavioral and cognitive neuroscience, functional neuroimaging imaging, and psychological clinical therapeutics to outline a series of studies with the long-term objective of delineating the neural substrates of anxiety disorders. The principal objective of this competitive renewal is to build on the applicants' previously accomplished work in non-clinical individuals with anxiety proneness and apply this to patients with anxiety disorders with the following specific aims: (1) To develop a basic systems neuroscience endophenotype for anxiety disorders. Based on our prior work, we hypothesize that, compared to healthy controls (HC), patients with GAD or PD will show increased activation of the anterior insula during various types of emotion processing that engage interoceptive systems. Moreover, we hypothesize that there is less functional coupling between the insular cortex and both the amygdala and the medial prefrontal cortex (mPFC) in patients with anxiety disorders. (2) To evaluate effects of CBT on the neural systems hypothesized to be dysfunctional in patients with anxiety disorders. We expect that successful treatment will be associated with attenuation of insular cortex activity and increased coupling between insula and both amygdala and mPFC, respectively. In the case of GAD, we also expect to see a reduction in task-related dorsolateral prefrontal cortex (DLPFC) activity. Anxiety disorders are early onset, prevalent, serious conditions that impact adversely on individual and societal functioning. Improved understanding of the neural circuitry of anxiety disorders will inform diagnostic conceptualizations and enable the more directed development and testing of novel therapies that are based on a more thorough understanding of pathophysiology, thereby conveying new therapeutic options to the many patients with anxiety disorders for whom existing treatments are inadequate.