Neural Mechanisms of Response Inhibition Training for Obsessive-Compulsive Disorder and Related Conditions - 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.
