The course of the neural correlates of reversal learning in obsessive–compulsive disorder and major depression: A naturalistic follow-up fMRI study

Reversal learning (RL) is impaired in obsessive–compulsive disorder (OCD) as well as in major depressive disorder (MDD). It is yet unknown to what extent pathophysiological mechanisms are state-dependent. Neural activation patterns during RL were measured using event-related functional magnetic resonance imaging (fMRI) reversal learning in patients with OCD (N=18) and MDD (N=15). A naturalistic follow-up design enabled investigation of the relationship between changes in clinical state, task performance and task-related neural activation over time. During follow-up, disease severity decreased significantly in both groups. Whereas task speed improved trend-significantly, task accuracy was unchanged. Task-related dorsal frontal-striatal activation decreased at follow-up in MDD, but increased in OCD. In both groups, symptom improvement was associated with reward-related changes in neural activation in the putamen and the orbitofrontal cortex. In both OCD and MDD, symptom reduction over time was associated with partial normalization of task-related activation patterns in brain regions. Whereas in OCD this normalization was characterized by increased recruitment of previously hypoactive frontal-striatal brain regions (i.e. dorsal frontal-striatal failure), in MDD previously hyperactive brain regions (frontal-striatal inefficiency), were recruited less after recovery. These results show that in both disorders frontal-striatal dysfunction is at least partly state-dependent.