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

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.