Neural Mechanisms of Response Inhibition Training for Obsessive-Compulsive Disorder and Related Conditions

强迫症及相关病症反应抑制训练的神经机制

• 批准号: 10431320
• 负责人: Christine L Larson
• 金额: $ 74.39万
• 依托单位: UNIVERSITY OF WISCONSIN MILWAUKEE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10431320
• 关键词: Adult; Adverse effects; Attention deficit hyperactivity disorder; Basal Ganglia; Behavior Therapy; Behavior monitoring; Behavioral; Binge Eating; Brain; Clinical; Cognitive; Data; Development; Disease; Dose; Educational Intervention; Electrophysiology (science); Failure; Goals; Impairment; Individual; Inferior; Intervention; Knowledge; Link; Literature; Measures; Mediating; Monitor; Neurocognitive Deficit; Obsessive compulsive behavior; Obsessive-Compulsive Disorder; Outcome; Participant; Patients; Performance; Pharmacological Treatment; Phase; Placebos; Process; Provider; Public Health; Randomized; Randomized Clinical Trials; Research; Research Domain Criteria; Skin; Specific qualifier value; Specificity; Substance Use Disorder; Symptoms; System; Therapeutic; Training; Training Programs; Translating; Trichotillomania; base; behavioral impairment; behavioral response; clinical practice; cognitive control; cognitive process; cognitive training; comparison group; computerized; confirmatory trial; cost efficient; design; dosage; effectiveness evaluation; efficacious treatment; endophenotype; follow-up; frontal lobe; functional outcomes; improved; indexing; innovation; neurobehavioral; neuroimaging; neuromechanism; novel; patient subsets; personalized medicine; portability; post intervention; reduce symptoms; relating to nervous system; response; sound; stem; success; symptomatology; treatment responders

PROJECT SUMMARY The impaired ability to suppress an inappropriate but pre-potent response (response inhibition; RI) characterizes several debilitating clinical problems, including obsessive-compulsive and related disorders (OCRD) such as obsessive-compulsive disorder, trichotillomania, and skin picking disorder. There is a critical need to develop an effective and durable treatment for OCRDs with demonstrable evidence for impacting impaired RI, a transdiagnostic intervention target specified in the Research Domain Criteria (RDoC) Cognitive Control systems. The objective of our R61/R33 application is to 1) examine the impact of a novel computerized intervention, response inhibition training (RIT), on neural indices of RI, and 2) examine the mechanistic link between engagement of the neural RI targets and change in symptoms in a randomized clinical trial for individuals with OCD, trichotillomania, and/or skin picking disorders. The R61 phase aims to examine whether RIT can attain the predetermined criterion-level change in neural RI indices (i.e., activation in right inferior frontal cortex; rIFC) (Aim1). Adults with OCRD (N=48) will be randomized to RIT or placebo training (PLT), with neural indices of RI assessed at pre- and post-intervention. If the rIFC is successfully engaged as a valid target, the RIT should show a greater level of rIFC activation during a RI task at both between-groups and within- group levels. The R61 “go/no-go” decision will be made by two effect size-based criteria: 1) η2=.06 or greater in a between-groups comparison; and 2) d=.5 or greater in a within-group pre-post RIT comparison. The R33 phase aims to determine the effectiveness of RIT in improving OCRD symptoms (Aim2a), and to examine whether the reduction in OCRD symptoms is mediated by changes in neural RI indices (Aim2b). To this end, Adults with OCRD (N=70) will be randomized to RIT or PLT, with pre-to-post neural measures of RI and pre-to- follow-up measures of OCRD symptoms. In both phases the RIT dosage (number of sessions) will be individually quantified and adjusted based on the ongoing monitoring of the behavioral RI process. Resulting data are expected to guide the development of RIT as a personally-optimizable intervention with a demonstrated neurobehavioral mechanism of action for treating OCRD. This contribution is significant as it can result in a transdiagnostically-applicable intervention capable of therapeutically modifying RI deficits. Our approach is innovative because it proposes a fundamentally different therapeutic approach to OCRD using a computerized, engaging (gamified), accessible, and cost-efficient intervention that can be easily implemented and disseminated. Further, in our personalized-medicine approach, we will examine the feasibility of an individually-optimizable intervention with a precise dose-control capability by monitoring the status of behavioral RI target. These innovative features highlight the substantial public health impact afforded by our effort to translate the accumulated neurobehavioral literature for RI processes to a widely applicable intervention for RI-implicated problems.

项目摘要 抑制不适当但优势反应的能力受损（反应抑制; RI） 以几种使人衰弱的临床问题为特征，包括强迫症和相关疾病 强迫症（OCRD），如强迫症、震颤症和皮肤采摘障碍。存在一个临界 需要为OCRD开发一种有效和持久的治疗方法，并有可证实的证据表明， RI受损，是研究领域标准（RDoC）中规定的跨诊断干预目标。 控制系统。我们的R61/R33应用程序的目的是1）检查一种新型计算机化的 干预，反应抑制训练（RIT），对RI的神经指标，和2）检查机械联系 在一项随机临床试验中， 患有强迫症、震颤症和/或皮肤采摘障碍的个体。R61阶段的目的是检查是否 RIT可以达到神经RI指数的预定标准水平变化（即，右下激活 额叶皮质; rIFC）（Aim 1）。患有OCRD的成人（N=48）将被随机分配至RIT或安慰剂训练（PLT）， 在干预前后评估RI的神经指标。如果rIFC被成功地用作有效目标， 在RI任务期间，RIT应在组间和组内显示更高水平的rIFC激活- 组水平。R61“通过/不通过”决定将通过两个基于效应量的标准做出：1）η2=.06或更大， 组间比较; 2）组内RIT前后比较中d= 0.5或更大。R33 阶段的目的是确定RIT在改善OCRD症状（Aim 2a）方面的有效性，并检查 神经RI指数的变化是否介导了OCRD症状的减轻（Aim 2b）。为此目的， 患有OCRD的成年人（N=70）将被随机分配到RIT或PLT组，测量术前至术后的RI和术前至术后的 OCRD症状的随访措施。在这两个阶段，RIT剂量（疗程数）将 基于对行为RI过程的持续监测单独量化和调整。所得 数据预计将指导RIT的发展，作为一种个人优化干预， 证实了治疗OCRD的神经行为作用机制。这一贡献是重要的，因为它可以 导致能够在治疗上改变RI缺陷的跨诊断适用的干预。我们 这种方法是创新的，因为它提出了一种与OCRD完全不同的治疗方法， 易于实施的计算机化、吸引人（游戏化）、可访问且具有成本效益的干预措施 并传播。此外，在我们的个性化医疗方法中，我们将研究 具有精确剂量控制能力的个体优化干预， 行为RI目标。这些创新的特点突出了我们的公共卫生所带来的巨大影响， 努力将积累的RI过程的神经行为文献转化为广泛适用的 干预RI相关问题。