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，如果不进行有效治疗， 可能导致终身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）是金标准，一线治疗儿童 然而，多达40%的儿童强迫症患者未能缓解。EXRP要求儿童故意 体验与他们的强迫性行为相关的痛苦，同时避免参与他们通常的强迫性行为。 旨在减少或消除痛苦的仪式。因此，为了有效，EXRP取决于患者的 灵活调整思维和行为的能力，即，来进行认知控制我们的初步数据 现存的文献显示，认知控制能力的改变和大脑功能的改变， 强迫症儿童的基本任务控制回路。这项提案利用了一个对儿童友好的， 参与，计算机化的在家认知训练（CT）干预，以增强认知控制 能力（目标参与），以减少症状，并改善强迫症儿童的EXRP反应。 在R61阶段，将对60名患有强迫症的儿童（8至12岁）进行CT检查，以测试 认知控制的行为标志物;认知的显着内部改善是Go/No- 进入Criterion，进入R33阶段。R61还将探测最佳剂量，因为这是第一个 在儿童强迫症中测试这种干预的研究。具体来说，我们将探讨认知的变化， 训练2周和4周后的表现; 4周是以前用于ADHD儿童的剂量。 R33将在120名患有强迫症的儿童（8至12岁）中进行双盲随机对照试验。 根据R61，儿童将随机完成最佳剂量的CT或假训练 匹配的经验，但不针对认知控制。所有儿童将完成12周的 黄金标准手动EXRP。这将使我们能够探索活跃的CT如何参与我们的行为 与假手术对照相比，靶向和增强对EXRP的反应。我们将进一步探讨 任务控制到默认模式网络连接前到后CT作为可能的神经作用机制。 将此CT用于新人群并评价神经科学衍生靶点的变化如何与 儿童强迫症症状的变化直接响应了NIMH对实验治疗的呼吁 并解决了迫切需要新的干预措施来治疗强迫症。此外，计算机化，在家里 CT代表了一种高度可扩展的干预措施，既可以增强现有治疗， 在严重疾病发作前进行早期干预的潜力。

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.