Cognitive control targets for the treatment of obsessive compulsive disorder in young children

抽象的。强迫症(OCD)通常在儿童时期发病，如果没有有效的治疗， 可能导致终生疾病和不良的功能结果。认知行为疗法(CBT) 暴露和反应预防(EXRP)是治疗儿童霍乱的黄金标准，一线治疗 然而，多达40%的儿科患者无法缓解强迫症。EXRP要求儿童故意 体验与他们的强迫症相关的痛苦，同时克制住他们通常的强迫症 旨在减轻或消除痛苦的仪式。因此，EXRP的有效性取决于患者的 灵活调整思维和行为的能力，即进行认知控制的能力。我们的初步数据 现存的文献表明，认知控制的能力和大脑功能的改变 强迫症儿童的潜在任务控制(TC)回路这项建议利用了一种对儿童友好的 参与式、计算机化的家庭认知训练(CT)干预，以增强认知控制 强迫症儿童减轻症状和改善EXRP反应的能力(目标参与)。 在R61阶段，CT将被提供给60名患有强迫症的儿童(8至12岁)，以测试在 认知控制的行为标记物；人内认知的显著改善是通过/不通过- Go Critarion进入R33阶段。R61还将探索最佳剂量，因为这是第一次 在儿童强迫症中测试这种干预措施的研究。具体地说，我们将探索认知方面的变化 在2周和4周的训练后表现良好；4周是以前用于ADHD儿童的剂量。 R33将对120名患有强迫症的儿童(8至12岁)进行双盲随机对照试验。 根据R61，儿童将被随机选择完成最佳剂量的CT，或进行假训练 在体验上与之匹配，但不针对认知控制。然后所有的孩子将完成12周的 黄金标准手册EXRP。这将使我们能够探索活跃的CT如何参与我们的行为 与假对照相比，靶向并增强了对EXRP的反应。我们将进一步探索在 任务控制将默认模式的网络连通性作为CT前后的一种可能的神经作用机制。 在新的人群中使用这种CT，并评估神经科学派生的靶点的变化是如何相关的 对儿童强迫症症状变化的直接响应NIMH呼吁实验疗法 并解决了对治疗强迫症的新干预措施的迫切需要。此外，电脑化、居家 CT代表了一种高度可扩展的干预措施，既可以增强现有的治疗方法，也可以 有可能成为严重疾病发作前的早期干预措施。

Abstract. Obsessive-Compulsive Disorder (OCD) often onsets in childhood and, if not effectively treated, can lead to lifelong illness and poor functional outcomes. Cognitive behavioral therapy (CBT) with exposure and response prevention (EXRP) is the gold-standard, first-line treatment for children with OCD, however, as many as 40% of pediatric patients fail to remit. EXRP requires children to deliberately experience distress associated with their obsessions while refraining to engage in their usual compulsive rituals aimed at reducing or neutralizing distressed. Thus, to be effective, EXRP depends on the patient's capacity to flexibly adapt thinking and behavior, i.e., to engage cognitive control. Our preliminary data and the extant literature show an altered capacity for cognitive control and altered functioning of underlying task control (TC) circuits in children with OCD. This proposal leverages a child-friendly, engaging, computerized at-home cognitive training (CT) intervention to enhance cognitive control capacity (target engagement) to reduced symptoms and improve EXRP response in children with OCD. In the R61 phase, CT will be delivered to 60 children (8 to 12 years) with OCD to test improvements in behavioral markers of cognitive control; significant within-person improvement in cognition is the Go/No- Go Criterion to progress to the R33 phase. The R61 will also probe optimal dosing as this is the first study to test this intervention in pediatric OCD. Specifically, we will probe change in cognitive performance after 2 and 4 weeks of training; 4 weeks is the dose previously used in children with ADHD. The R33 will entail a double-blind randomized control trial in 120 children (8 to 12 years) with OCD. Children will be randomized to complete the optimal dose of CT, per the R61, or a sham training matched for experience but not targeting cognitive control. All children will then complete 12 weeks of gold-standard manualized EXRP. This will allow us to probe how active CT engages our behavioral target and augments response to EXRP, compared to a sham control. We will further explore changes in task control to default mode network connectivity pre- to post-CT as a likely neural mechanism of action. Using this CT with a novel population and evaluating how changes in neuroscience-derived targets relate to changes in OCD symptoms in children directly responds to NIMH call for experimental therapeutics and addresses an urgent need for novel interventions to treat OCD. Furthermore, computerized, at-home CT represents a highly scalable intervention both to augment existing treatments as well as having potential as an early intervention before onset of severe illness.