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

Objectives 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. Methods 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. Results 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. Conclusions 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