Improving the Control of Fear: Healthy Adults to Pathological Anxiety

 描述(由申请人提供)：建议的R00研究将在德克萨斯大学奥斯汀分校进行，是K99独立之路奖指导研究的延伸。这项研究的目的是探索新的实验技术，以提高焦虑病理中直接控制恐惧的能力。焦虑症是最常见的精神疾病，据估计，12个月的患病率约为4000万美国成年人。恐惧条件作用的理论和技术方面继续为描述和理解恐惧和焦虑的病因、维持和治疗提供了一个有价值的模型。治疗领域的一个例子是暴露疗法，它是基于消退原则的。然而，著名的学习理论模型早就认识到灭绝作为一种治疗工具的缺点；灭绝是一种脆弱的学习形式，无法概括，恐惧行为往往会随着时间的推移而回归。过去20年的临床研究表明，在各种焦虑症类别消失后，控制恐惧表达的能力存在严重缺陷，包括创伤后应激障碍、恐慌症和恐惧症。对灭绝极限的实验室研究可以解释为什么许多严重的恐惧和焦虑在临床治疗后会复发。因此，有强烈的动机开发创新的行为技术来改善对恐惧的控制，以便适应不良的恐惧和焦虑对治疗更敏感，更不容易复发。然而，关于改善人类恐惧控制的新技术的系统神经行为研究受到的关注有限。在纽约大学进行的这个奖项的指导阶段，候选人结合了关于恐惧消退的理论、技术和经验方面的新培训，以测试新的行为技术，以使用功能磁共振成像和心理生理学方法相结合的方法来改善健康成年人的恐惧控制。目标1希望通过向参与者引入令人惊讶的、新颖的、无威胁的关联来超越不适应的威胁关联。目标2旨在通过在多种不同的虚拟现实环境下进行灭绝来促进灭绝学习的概括性。R00项目将发扬这一知识，在临床焦虑人群中研究这两项新的实验任务，这些人群的特征是无法控制标准消退程序后的恐惧表达。在临床人群中的研究是通过在指导阶段开发的临床研究中的新的监督培训来促进的。这里提出的研究有可能推进精神病理学的生物学模型，建立恐惧和焦虑障碍的神经行为风险/弹性因素，并最终为病理性焦虑的创新和更有效的治疗干预做出贡献。

 DESCRIPTION (provided by applicant): The proposed R00 research will be conducted at the University of Texas at Austin, and is an extension of a mentored K99 research on a Pathway to Independence Award. The objective of this research is to investigate new experimental techniques to improve the control of fear directly in anxiety pathologies. Anxiety pathologies are the most common mental illness, with a 12-month prevalence estimate of about 40 million American adults. Theoretical and technical aspects of fear conditioning continue to provide a valuable model to characterize and understand the etiology, maintenance, and treatment for pathologies of fear and anxiety. An example in the treatment domain is exposure therapy, which is based on the principles of extinction. However, prominent learning theory models have long recognized the shortcomings of extinction as a therapeutic tool; extinction is a fragile form of learning that fails to generalize, and fear behaviors tend to return over time. Clinical research in the past two decades has revealed serious deficits in the ability to control fear expression following extinction across anxiety disorder categories, including posttraumatic stress disorder, panic disorder, and phobias. Laboratory research on the limits to extinction can describe why many severe fears and anxieties relapse following clinical treatment. Accordingly, there is strong motivation to develop innovative behavioral techniques to improve the control of fear so that maladaptive fears and anxieties are more responsive to treatment and less prone to relapse. Yet, systematic neurobehavioral research on novel techniques to improve the control of fear in humans has received limited attention. During the mentored phase of this award conducted at New York University, the candidate incorporated new training on theoretical, technical, and empirical aspects of fear extinction to test new behavioral techniques to improve the control of fear in healthy adults using combination functional magnetic resonance imaging and psychophysiology methods. Aim 1 looked to override maladaptive threat associations by introducing surprising, novel, non-threat associations to the participant. Aim 2 looked to promote the generalizability of extinction learning by conducting extinction under multiple different virtual reality contexts. The R00 project will carry forward this knowledge to investigate these two new experimental tasks in clinical anxiety populations characterized by the inability to control fear expression following standard extinction procedures. Research in clinical populations was fostered by new supervised training in clinical research developed during the mentored phase. The research proposed here has the potential to advance biological models of psychopathology, establish neurobehavioral risk/resilience factors for disorders of fear and anxiety, and ultimately contribute to innovative and more effective therapeutic interventions for pathological anxiety.