Background: Compulsive behaviors in Obsessive-Compulsive Disorder (OCD) areposited to be negatively reinforced via short-term negation of distress-inducingtriggers, but neural activity during negative reinforcement in the context ofOCD remains poorly understood.Methods: In 18 people with OCD and 16 healthy matched comparison subjectscompleting functional MRI, we tested the effect of a novel negativereinforcement behavioral paradigm. Three visual stimulus types(Compulsion-Related, Negative, Neutral) were displayed in the scanner andremoved by participants pressing a button, yielding two analysis epochs: imagepresentation and image removal.Results: OCD patients showed a larger increase in medial orbitofrontal cortex(mOFC; BA11) activation after image removal that was specific tocompulsion-related images. People with OCD also showed altered patterns ofdeactivation following compulsion-related and negative image removal in theright and left amygdala, respectively. People with OCD also showed largerdeactivations in the ventral tegmental area (VTA) after removal of all imagetypes, and increased overall activation to negative images in the right nucleusaccumbens (NAcc).Conclusion: We provide initial data demonstrating altered neural activity duringnegative reinforcement in OCD patients, providing empirical support for dominantbehavioral models emphasizing the role of negative reinforcement in etiology andmaintenance of pathological compulsive behaviors.