Psychological Medicine

Original Articles

Differential frontal–striatal and paralimbic activity during reversal learning in major depressive disorder and obsessive–compulsive disorder

P. L. Remijnsea1a2 c1, M. M. A. Nielena1, A. J. L. M. van Balkoma1a3, G.-J. Hendriksa4a5, W. J. Hoogendijka1a3, H. B. M. Uylingsa2a6a7 and D. J. Veltmana1a2a3

a1 Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands

a2 Amsterdam, The Netherlands

a3 Out-patient Academic Clinic for Anxiety and Mood Disorders, GGZ Buitenamstel, Amsterdam, The Netherlands

a4 Out-patient Clinic for Anxiety Disorders, GGZ Nijmegen, The Netherlands

a5 Department of Psychiatry, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

a6 Department of Anatomy and Neuroscience, VU University Medical Center, Amsterdam, The Netherlands

a7 School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, University of Maastricht, The Netherlands


Background Several lines of research suggest a disturbance of reversal learning (reward and punishment processing, and affective switching) in patients with major depressive disorder (MDD). Obsessive–compulsive disorder (OCD) is also characterized by abnormal reversal learning, and is often co-morbid with MDD. However, neurobiological distinctions between the disorders are unclear. Functional neuroimaging (activation) studies comparing MDD and OCD directly are lacking.

Method Twenty non-medicated OCD-free patients with MDD, 20 non-medicated MDD-free patients with OCD, and 27 healthy controls performed a self-paced reversal learning task in an event-related design during functional magnetic resonance imaging (fMRI).

Results Compared with healthy controls, both MDD and OCD patients displayed prolonged mean reaction times (RTs) but normal accuracy. In MDD subjects, mean RTs were correlated with disease severity. Imaging results showed MDD-specific hyperactivity in the anterior insula during punishment processing and in the putamen during reward processing. Moreover, blood oxygen level-dependent (BOLD) responses in the dorsolateral prefrontal cortex (DLPFC) and the anterior PFC during affective switching showed a linear decrease across controls, MDD and OCD. Finally, the OCD group showed blunted responsiveness of the orbitofrontal (OFC)–striatal loop during reward, and in the OFC and anterior insula during affective switching.

Conclusions This study shows frontal–striatal and (para)limbic functional abnormalities during reversal learning in MDD, in the context of generic psychomotor slowing. These data converge with currently influential models on the neuropathophysiology of MDD. Moreover, this study reports differential neural patterns in frontal–striatal and paralimbic structures on this task between MDD and OCD, confirming previous findings regarding the neural correlates of deficient reversal learning in OCD.

(Received February 01 2008)

(Revised September 15 2008)

(Accepted December 04 2008)

(Online publication January 27 2009)


c1 Address for correspondence: P. L. Remijnse, M.D., VU University Medical Center, Department of Anatomy and Neurosciences, room G102B, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. (Email: