1/2 Task control circuit targets for obsessive compulsive behaviors in children

点击翻译按钮获取中文摘要

Abstract. Subclinical Obsessive-Compulsive symptoms (OCS) in early development increase risk for OC- related impairment in adulthood, but wax and wane in middle childhood, suggesting a critical period for overcoming symptoms. Clinically significant OCS (Obsessive compulsive Disorder, OCD) also emerge during school age and also follow a variable course --- some patients remit, while others continue to suffer OCS, even after gold standard, cognitive behavioral therapy (CBT). Such different OCS trajectories may derive from differential engagement of cognitive control circuits, specifically fronto-parietal (FP) and cingulo-opercular (CO) task control (TC) circuits, since the normal development of these circuits parallels the maturation of cognitive control processes that are altered in pediatric OCD. Modulation of TC circuits could help to reduce childhood OCS, but identification of the specific changes in TC circuits that coincide with OCS reductions is first required. Our preliminary data suggests that TC alterations (e.g., increased or decreased activation) and associations with OCS depend on the specific TC circuit (CO or FP) and component cognitive control process engaged (i.e., conflict resolution, error processing), as well as the age, medication status and clinical severity of the patients studied. Accordingly, we will administer two cognitive control tasks embedded within a multi-modal imaging protocol, using pulse sequences consistent with the Adolescent Brain and Cognitive Development study and Human Connectome Project. We will use these cutting-edge MRI sequences to elucidate how TC circuit changes associate with OCS reductions in unmedicated children, aged 7-12 years. Drawing from the RDoC framework, imaging, behavioral, and clinical/self-report measures of symptoms will be collected in a large sample of children with OCD, subclinical OCS or no OCS (n = 180 total), recruited across 2 sites. Leveraging the normal to abnormal range of OCS represented by the combined sample, we will test the relation of TC circuitry and cognitive control processes with OCS across the full spectrum of severity (Aim 1). In OCD- affected children, OCS will then be manipulated with a standard, 16-week course of CBT to determine how TC circuit changes associate with changes in OCS severity across the remission, partial response and no response outcomes known to occur after CBT (Aim 2). Circuit-based changes will be compared to non-specific changes in healthy children who remain OCS-free. By pinpointing which cognitive control processes and TC circuit changes associate with reductions in OCS, this work will inform the selection of processes and neural targets to direct cognitive trainings to treat and prevent childhood OCS, setting the stage for future clinical trials.