Aberrant functional connectivity of dorsolateral prefrontal and cingulate networks in patients with major depression during working memory processing

Background: In patients with major depressive disorder (MDD), functional neuroimaging studies have reported an increased activation of the dorsolateral prefrontal cortex (DLPFC) during executive performance and working memory (WM) processing, and also an increased activation of the anterior cingulate cortex (ACC) during baseline conditions. However, the functional coupling of these cortical networks during WM processing is less clear. Method: In this study, we used a verbal WM paradigm, event-related functional magnetic resonance imaging (fMRI) and multivariate statistical techniques to explore patterns of functional coupling of temporally dissociable dorsolateral prefrontal and cingulate networks. By means of independent component analyses (ICAs), two components of interest were identified that showed either a positive or a negative temporal correlation with the delay period of the cognitive activation task in both healthy controls and MDD patients. Results: In a prefronto-parietal network, a decreased functional connectivity pattern was identified in depressed patients comprising inferior parietal, superior prefrontal and frontopolar regions. Within this cortical network, MDD patients additionally revealed a pattern of increased functional connectivity in the left DLPFC and the cerebellum compared to healthy controls. In a second, temporally anti-correlated network, healthy controls exhibited higher connectivity in the ACC, the ventrolateral and the superior prefrontal cortex compared to MDD patients. Conclusions: These results complement and expand previous functional neuroimaging findings by demonstrating a dysconnectivity of dissociable prefrontal and cingulate regions in MDD patients. A disturbance of these dynamic networks is characterized by a simultaneously increased connectivity of the DLPFC during task-induced activation and increased connectivity of the ACC during task-induced deactivatio