Neural Dimensions of Attention Bias Modification for Transdiagnostic Anxiety

描述（由申请人提供）：目前临床焦虑的一线治疗表现出50-70%的反应平台，复发率高，缓解率低，几乎没有证据表明哪些患者可以从哪种治疗方案中受益。朝着更高效和有效的精神病学治疗方法发展的障碍可能包括：对治疗结果的理论驱动的、机制预测因素的关注不足；使用异质性治疗方案，需要专家管理，并有多种可能的机制；而目前的精神病学诊断分类学，可能会模糊生物行为功能的关键、跨诊断维度。候选人的长期目标是通过增加对神经认知的跨诊断维度的关注来改善临床焦虑治疗的结果。这些工作具有以下潜力：1)指导改进和发展新的机制，“神经行为”治疗方法，或通过行为方法靶向大脑机制的治疗方法；2)微调特定方法的临床适应症，例如，通过描述特定神经行为治疗针对（或不针对）焦虑病理生理学的特定方面。候选人的当前重点是研究过度关注威胁的神经机制，并利用基于计算机的训练干预，注意偏差修正（ABM）直接针对这些机制。从理论上讲，对威胁的过度关注是慢性焦虑症状和相关负面健康后果的关键因素。ABM直接针对这一机制，是一种高成本效益的干预措施，其对临床焦虑人群的疗效得到了迅速增长的实证支持。候选人通过研究焦虑中威胁处理的神经机制，并将这些神经维度与ABM结果联系起来，寻求桥梁基础和应用研究领域。目前的指导病人导向的职业发展奖将独特地定位候选人，以推进她的长期研究议程。除了临床心理学、统计学、研究方法和认知情感神经科学方面的广泛培训外，她的背景还包括对焦虑威胁的注意神经机制的专门培训、基本的功能磁共振成像方法、对神经行为治疗研究的初步接触。她试图加深、扩展和整合她之前的训练，接受额外的训练：1)威胁处理的神经回路；2)先进的功能磁共振成像方法；3)临床试验研究——包括疗效测试的基本方法、神经机制测试和预后预测的先进方法。匹兹堡大学是一个优秀的环境，从事跨学科的培训需要实现这些培训目标。候选人的导师greg Siegle（匹兹堡大学）、David Brent（匹兹堡大学）和Nader Amir（圣地亚哥州立大学）在先进的功能磁共振成像方法、焦虑和威胁处理的神经和注意力机制、临床试验研究、神经行为治疗以及神经预测和治疗结果机制方面拥有专业知识。团队的个人生产力的集体记录，强大的指导历史，以及跨学科的合作使他们非常适合指导候选人的轨迹。的

DESCRIPTION (provided by applicant): Current first-line treatments for clinical anxiety exhibit a 50-70% response plateau, with high rates of relapse, low rates of remission, and little evidence to suggest which patients may benefit from which treatment options. Barriers to progress towards a more efficient and effective approach to psychiatric care may include inadequate focus on theory-driven, mechanistic predictors of treatment outcome; the use of heterogeneous treatment protocols that require expert administration and have multiple likely mechanisms; and the current diagnostic nosology of psychiatry, which may obscure critical, transdiagnostic dimensions of biobehavioral functioning. The candidate's long-term ambition is to improve outcomes in clinical anxiety treatment through an increased focus on transdiagnostic dimensions of neurocognition. Such work has the potential to 1) guide refinement and development of novel mechanistic, "neurobehavioral" treatment approaches, or treatments that target brain mechanisms through behavioral methods, and 2) fine-tune the clinical indications of specific approaches, e.g., by characterizing the specific aspects of anxiety pathophysiology that are (and are not) targeted by specific neurobehavioral treatments. The candidate's immediate focus is to study neural mechanisms of excessive attention to threat and target these mechanisms directly using a computer-based training intervention, attention bias modification (ABM). Excessive attention to threat is theorized to be a critical contributor to chronic anxiety symptoms and related negative health consequences. ABM, which directly targets this mechanism, is a highly cost-effective intervention with rapidly growing empirical support for its efficacy in clinically anxious populations. The candidate seeks to bridge basic and applied research domains by investigating neural mechanisms of threat processing in anxiety and relating these neural dimensions to ABM outcome. The current Mentored Patient Oriented Career Development Award will uniquely position the candidate to advance her long-term research agenda. Her background includes specialized training in neural mechanisms of attention to threat in anxiety, basic fMRI methods, and preliminary exposure to neurobehavioral treatment research, in addition to broad training in clinical psychology, statistics, research methods, and cognitive- affective neuroscience. She seeks to deepen, extend, and integrate across her previous training, receiving additional training in 1) neural circuitry of threat processing; 2) advanced fMRI methods; and 3) clinical trials research-including basic methods for testing efficacy and advanced methods for testing neural mechanisms and predictors of outcome. The University of Pittsburgh is an outstanding environment in which to engage in the interdisciplinary training required to achieve these training goals. The candidate's mentors-Greg Siegle (University of Pittsburgh), David Brent (University of Pittsburgh), and Nader Amir (San Diego State University)-have combined expertise in advanced fMRI methods, neural and attentional mechanisms of anxiety and threat processing, clinical trials research, neurobehavioral treatments, and neural predictors and mechanisms of treatment outcome. The team's collective record of individual productivity, strong mentorship histories, and interdisciplinary collaboration makes them ideally suited to guide the candidate's trajectory. The proposed project draws on this training and expertise to examine two dimensions of attention to threat: initial vigilance and sustained bias towards threat. The proposed study will examine the neural correlates of each form of threat processing using an individual differences, transdiagnostic approach. 65 individuals with clinically disabling trait anxiety will complete fMRI tasks designed to capture these dissociable dimensions, as well as behavioral, self-report, and diagnostic measures. Participants will be randomly allocated to receive ABM (n=45), which is specifically designed to ameliorate initial vigilance to threat, or a sham intervention (n=20). A subset of ABM completers (n=20) will repeat fMRI assessments post-intervention. Data will be used to test a neural mechanistic model of ABM efficacy which posits that initial, but not sustained, neural processing of threat will be specifically targeted by ABM. Accordingly, the candidate will examine 1) neural mechanisms correlated with behavioral manifestations of initial and sustained attention to threat at baseline; 2) ABM effects on symptom-level, behavioral, and neural dimensions of initial and sustained threat processing; and 3) associations between baseline neural dimensions and ABM outcomes. These analyses will give the applicant valuable experience using an individual differences approach to understand anxiety pathophysiology and outcomes following a mechanistic treatment. They will also provide pilot data for future work in programmatic neurobehavioral treatment research. Future large-scale R01 studies will be designed to, e.g., further validate identified neural dimensions of threat processing as moderators and mediators of treatment outcome, translate fMRI predictors into clinically available forms, and develop new neurobehavioral approaches designed to target predictors of ABM non-response. Consistent with NIMH's Strategic Plan Strategy 1.4 and proposed Research Domain Criteria, the ultimate goal of this work is to promote a neurocognitive process-based framework for more effective patient classification and treatment.