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 抑制不适当但预先抗衡反应的能力受损（反应抑制； RI） 表征了几个令人衰弱的临床问题，包括强迫症和相关疾病 （OCRD），例如强迫症，毛毛虫病和皮肤采摘障碍。有关键 需要为OCRD开发有效耐用的治疗 RI受损，是研究领域标准（RDOC）认知中指定的经诊断干预目标 控制系统。我们的R61/R33应用的目的是1）检查新型计算机的影响 干预，反应抑制训练（RIT），RI神经指数和2）检查机械链接 在一项随机临床试验中，神经RI靶标的参与与症状的变化之间 患有强迫症，毛毛虫和/或皮肤拾取障碍的人。 R61阶段旨在检查是否是否 RIT可以实现神经RI指数的预定标准级变化（即在右下方激活 额叶皮层； RIFC）（AIM1）。 OCRD（n = 48）的成年人将被随机分为RIT或安慰剂训练（PLT）， RI的神经指数在干预前和干预后评估。如果RIFC成功地作为有效目标参与 在组间和内部的RI任务期间，RIT应显示更高水平的RIFC激活 小组级别。 R61“ GO/NO-GO”决定将由两个基于效应尺寸的标准做出：1）η2= .06或更大 组间比较； 2）d = .5或更大的组内post RIT比较。 R33 阶段旨在确定RIT在改善OCRD症状（AIM2A）中的有效性，并检查 OCRD症状的降低是否是由神经RI指数的变化介导的（AIM2B）。为此， 具有OCRD的成年人（n = 70）将被随机分为RIT或PLT，并具有RI和PRE-OT-OF-POST神经测量 OCRD症状的后续措施。在这两个阶段中，RIT剂量（会话数）将是 基于对行为RI过程的持续监控进行单独量化和调整。结果 希望数据将指导RIT的发展作为一种个人选择干预措施 证明了治疗OCRD的神经行为机制。这种贡献很重要，因为它可以 导致能够热修改RI缺陷的经诊断性的干预措施。我们的 方法具有创新性，因为它提出了一种从根本上使用的治疗方法 计算机化，引人入胜（配套），可访问和具有成本效益的干预措施，可以轻松实施 并传播。此外，在我们的个性化医学方法中，我们将研究 通过监视状态 行为RI目标。这些创新的功能突出了我们的实质性公共卫生影响 努力将RI过程的累积神经行为文献转化为广泛的适用 干预RI填充问题。