Neural basis of impaired safety signaling in Obsessive Compulsive Disorder

Significance Assigning safety to stimuli and situations forms an important part of everyday functioning. Obsessive Compulsive Disorder (OCD) is a prototypical disorder of inflexible behavior influenced by anxiety. Here we show, using neuroimaging of fear reversal learning, which involves a previously threatening stimulus becoming safe while a previously safe stimulus becomes threatening, that OCD patients fail to differentiate a safe from a threatening stimulus only after such a reversal, as measured by skin conductance responses. This OCD impairment in safety signaling, a likely prominent component of successful exposure therapy, is predicted and mediated by altered activity in a neural salience network including the ventromedial prefrontal cortex.