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.

项目概要 抑制不适当但预强反应的能力受损（反应抑制；RI） 描述了一些使人衰弱的临床问题，包括强迫症和相关疾病 （OCRD）如强迫症、拔毛癖、抓皮肤症等。 需要为 OCRD 开发一种有效且持久的治疗方法，并提供可证明的影响证据 RI 受损，研究领域标准 (RDoC) 认知中指定的跨诊断干预目标 我们的 R61/R33 应用程序的目标是 1) 检查新型计算机化的影响。 干预、反应抑制训练 (RIT)、RI 神经指数，以及 2) 检查机制联系 在一项随机临床试验中，神经 RI 目标的参与与症状变化之间的关系 R61 阶段旨在检查是否患有强迫症、拔毛癖和/或皮肤采摘障碍。 RIT 可以实现神经 RI 指数的预定标准水平变化（即右下肢激活） 患有 OCRD 的成人 (N=48) 将随机接受 RIT 或安慰剂训练 (PLT)。 干预前和干预后评估的 RI 神经指数 如果 rIFC 成功作为有效目标， 在 RI 任务期间，RIT 应在组间和组内显示更高水平的 rIFC 激活 R61“通过/不通过”决定将根据两个基于效应大小的标准做出：1) η2=.06 或更大。 组间比较；以及 2) 组内 RIT 前后比较中 d=0.5 或更大。 该阶段旨在确定 RIT 在改善 OCRD 症状方面的有效性（Aim2a），并检查 OCRD 症状的减轻是否是由神经 RI 指数的变化介导的（Aim2b）。 患有 OCRD 的成年人 (N=70) 将被随机分配至 RIT 或 PLT，并进行 RI 前后神经测量和 RI 前后神经测量 OCRD 症状的后续措施 在两个阶段中，RIT 剂量（疗程次数）均为 根据对行为 RI 结果的持续监控进行单独量化和调整。 预计数据将指导 RIT 的发展，作为一种个人优化的干预措施， 治疗 OCRD 的神经行为作用机制这一贡献非常重要。 产生跨诊断适用的干预措施，能够在治疗上改变 RI 缺陷。 该方法具有创新性，因为它提出了一种根本不同的 OCRD 治疗方法，使用 可以轻松实施的计算机化、参与性（游戏化）、可访问且具有成本效益的干预措施 此外，在我们的个性化医疗方法中，我们将研究这种方法的可行性。 通过监测个体的状态，具有精确剂量控制能力的个体优化干预 这些创新特征凸显了我们的行为对公共卫生的重大影响。 努力将积累的 RI 过程的神经行为文献转化为广泛适用的 RI 相关问题的干预。