Working-memory functional MRI in euthymic major depression

• ¹ Interdisciplinary Center for Clinical Research (IZKF FG4), University of Muenster, Germany
• ² Department of Psychiatry, University of Muenster, Germany
• ³ Department of Psychology, University of Muenster, Germany, Germany
• ⁴ Department of Psychiatry, Weill Medical College, Cornell University, United States
• ⁵ Department of Clinical Radiology, University of Muenster, Germany
• ⁶ Department of Psychiatry, School of Medicine, James Cook University, Australia
• ⁷ LWL-Klinik Muenster, Germany

Background: Cognitive impairments are well documented for the acute episode of Major Depressive Disorder (MDD). Much less is known about cognitive function in the euthymic state. In the acute episode of MDD dysfunctional activation of lateral prefrontal and cingulate cortex has been observed during working memory performance. The present study investigates working-memory function and its neurobiological correlate in euthymic MDD patients. We hypothesized that dysfunctional activation might persist when depressive symptoms improve.

Methods: We investigated 56 subjects functional magnetic resonance imaging (fMRI) at 3 Tesla. A classical verbal n-back task (0-, 1-, and 2-back) was used to challenge working-memory function in 28 well–characterized, euthymic, unipolar MDD patients and 28 healthy control subjects matched according to age, sex and education level. Data were analyzed using SPM5.

Results: We observed comparable overall patterns of brain activation in both groups in the absence of significant behavioral differences. Both groups showed stronger activation of the typical working-memory network with increasing memory load. Interestingly, significant hyperactivation of the cingulate cortex was observed in euthymic patients, while lateral prefrontal activation was comparable between patients and controls.

Conclusions: Functional MRI investigation of working-memory revealed a dissociation of lateral prefrontal and cingulate brain function in the euthymic state of MDD. Cingulate function, which is important for both emotional and cognitive processing and their integration, is abnormal when mood is restored. Our findings could reflect a different speed of normalization in prefrontal and limbic cortices, persistent systematic changes in neuronal networks after an episode of MDD, or alternatively a compensatory mechanism to maintain working-memory performance.