Neural Dimensions of Attention Bias Modification for Transdiagnostic Anxiety

跨诊断焦虑的注意偏差修正的神经维度

• 批准号: 8485272
• 负责人: Rebecca Price
• 金额: $ 15.5万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8485272
• 关键词: Address; Adult; Adverse effects; Anxiety; Anxiety Disorders; Applied Research; Attention; Basic Science; Behavioral; Brain; Chronic; Classification; Clinical; Clinical Psychology; Clinical Trials; Cognition; Cognitive; Computers; Data; Development; Diagnostic; Dimensions; Disease remission; Educational Intervention; Environment; Exhibits; Exposure to; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Health; Heterogeneity; Hyperactive behavior; Individual; Individual Differences; Internet; Intervention; K-Series Research Career Programs; Lead; Link; Literature; Masks; Measures; Mediator of activation protein; Medical; Mentors; Mentorship; Methods; Modeling; Modification; Morbidity - disease rate; Neurocognition; Neurocognitive; Outcome; Participant; Patient Self-Report; Patients; Pattern; Population; Positioning Attribute; Prefrontal Cortex; Process; Productivity; Psychiatric therapeutic procedure; Psychiatry; Public Health; Recording of previous events; Relapse; Relative (related person); Research; Research Methodology; Sampling; Severities; Staging; Stimulus; Strategic Planning; Symptoms; Testing; Time; Training; Translating; Treatment Protocols; Treatment outcome; Universities; Work; affective neuroscience; base; biobehavior; brain behavior; clinical anxiety; clinically relevant; computerized; cost effective; design; disability; disease classification; effective intervention; effective therapy; efficacy testing; emotional experience; experience; improved; indexing; interdisciplinary collaboration; neural circuit; neurobehavioral; neuromechanism; novel; patient oriented; post intervention; preconditioning; public health relevance; relating to nervous system; response; statistics; theories; therapy design; trait; vigilance

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.

描述（由申请人提供）：目前临床焦虑症的一线治疗表现出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能从哪些治疗方案中获益。障碍进展到一个更有效和更有效的方法，精神科护理可能包括不充分的重点理论驱动，治疗结果的机械预测;使用异质性的治疗方案，需要专家管理，并有多种可能的机制;和目前的诊断疾病分类学的精神病学，这可能会模糊的关键，transdiagnosis尺寸的生物行为功能。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。这些工作有可能1）指导改进和开发新的机制，“神经行为”治疗方法，或通过行为方法靶向大脑机制的治疗，以及2）微调特定方法的临床适应症，例如，通过表征焦虑病理生理学的特定方面，这些方面是（或不是）特定神经行为治疗的目标。 候选人的直接重点是研究过度关注威胁的神经机制，并直接使用基于计算机的训练干预，注意力偏差修正（ABM）来瞄准这些机制。对威胁的过度关注被认为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，是一种具有高度成本效益的干预措施，其在临床焦虑人群中的疗效得到了迅速增长的经验支持。候选人寻求通过调查焦虑中威胁处理的神经机制以及将这些神经维度与ABM结果联系起来，来弥合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的定位候选人，以推进她的长期研究议程。她的背景包括关注焦虑威胁的神经机制的专门培训，基本的功能磁共振成像方法，以及初步接触神经行为治疗研究，此外还有临床心理学，统计学，研究方法和认知情感神经科学的广泛培训。她寻求深化，扩展和整合她以前的培训，在1）威胁处理的神经回路中接受额外的培训; 2）先进的功能磁共振成像方法;和3）临床试验研究-包括测试功效的基本方法和测试神经机制和结果预测的先进方法。匹兹堡大学是从事实现这些培训目标所需的跨学科培训的优秀环境。候选人的导师格雷格·西格尔（匹兹堡大学）、大卫布伦特（匹兹堡大学）和纳德·阿米尔（圣地亚哥州立大学）结合了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、神经预测因子和治疗结果机制的专业知识。团队的个人生产力的集体记录，强大的导师历史，和跨学科的合作，使他们非常适合指导候选人的轨迹。 的 拟议项目利用这种培训和专门知识，审查对威胁的关注的两个方面：最初的警惕和对威胁的持续偏见。拟议的研究将使用个体差异，transdiagnosis方法检查每种形式的威胁处理的神经相关性。65名患有临床致残性特质焦虑的个体将完成功能磁共振成像 任务旨在捕捉这些可分离的维度，以及行为，自我报告和诊断措施。参与者将被随机分配接受ABM（n=45），该药物专门用于提高对威胁的初始警惕性，或假干预（n=20）。ABM完成者的一个子集（n=20）将在干预后重复fMRI评估。数据将用于测试ABM功效的神经机制模型，该模型假定ABM将专门针对威胁的初始但非持续神经处理。因此，候选人将检查1）与基线时对威胁的初始和持续关注的行为表现相关的神经机制; 2）ABM对初始和持续威胁处理的行为水平，行为和神经维度的影响;以及3）基线神经维度和ABM结果之间的关联。这些分析将为申请人提供宝贵的经验，使用个体差异方法来了解焦虑的病理生理学和机械治疗后的结果。他们还将为未来的程序化神经行为治疗研究提供试点数据。未来的大规模R 01研究将设计为，例如，进一步验证已确定的威胁处理的神经维度作为治疗结果的调节者和介导者，将fMRI预测因子转化为临床可用的形式，并开发新的神经行为方法，旨在针对ABM无反应的预测因子。与NIMH的战略计划策略1.4和拟议的研究领域标准相一致，这项工作的最终目标是促进基于神经认知过程的框架，以实现更有效的患者分类和治疗。