Characterization and Modulation of Functional Connectivity and Fear Extinction Abnormalities in Obsessive-Compulsive Disorder

ABSTRACT Approximately 60% of patients with obsessive-compulsive disorder (OCD) respond to the psychotherapy of choice, exposure and response prevention (ERP). Unfortunately, troubling symptoms persist for most patients, even treatment responders. ERP is believed to depend on safety learning and engagement of related brain

circuitry. OCD patients have repeatedly demonstrated deficits in safety learning and memory processes, but important gaps exist in this literature. In particular, there are limited data on neural functions related to safety learning and memory deficits in OCD. This is important as multiple studies have shown that OCD is associated

with dysconnectivity in large-scale networks that are implicated in fear signaling and to safety learning, namely, the default mode network (DMN) and salience network (SN). Preliminary research by the PI suggests that that anodal (excitatory) frontopolar (over the anterior medial prefrontal cortex [mPFC]) multifocal transcranial direct

current stimulation (tDCS) reduced resting functional connectivity between these networks and accelerates safety learning in community volunteers. Preliminary research by the PI also suggests that frontopolar tDCS accelerates safety learning during a single session of in vivo ERP with patients diagnosed with OCD. The

proposed R01 project would be the first to examine if OCD is associated with deficits in inhibitory safety learning – fear extinction learning that is acquired after original fear conditioning has been consolidated into long-term memory – and would be among the first to probe neural functions associated with extinction deficits

in OCD. The proposed R01 project would also replicate and extend the PI’s exciting preliminary findings to test if frontopolar tDCS can normalize dysconnectivity and functional activity within and between the DMN and SN and recover safety learning deficits in patients with OCD. Results from this project would pave the way for

additional experimental therapeutics target engagement research; research that examine the effects of frontopolar tDCS on neural abnormalities and safety learning deficits in other anxious psychopathology (e.g., posttraumatic stress disorder) and clinical trials examining the interactive effects of frontopolar tDCS and ERP

on brain dysconnectivity and symptoms of OCD.