Altered functional connectivity density in major depressive disorder at rest.

Major depressive disorder is characterized by abnormal brain connectivity at rest. Currently, most studies investigating resting-state activity rely on a priori restrictions on specific networks or seed regions, which may bias observations. We hence sought to elicit functional alterations in a hypothesis-free approach. We applied functional connectivity density (FCD) to identify abnormal connectivity for each voxel in the whole brain separately. Comparing resting-state fMRI in 21 MDD patients and 23 matched healthy controls, we identified atypical connections for regions exhibiting abnormal FCD and compared our results to those of an independent component analysis (ICA) on networks previously investigated in MDD. Patients showed reduced FCD in mid-cingulate cortex (MCC) and increased FCD in occipital cortex (OCC). These changes in global FCD were driven by abnormal local connectivity changes and reduced functional connectivity (FC) toward the left amygdala for MCC, and increased FC toward the right supplementary motor area for OCC. The altered connectivity was not reflected in ICA comparison of the salience and visual networks. Abnormal FC in MDD is present in cingulate and OCC in terms of global FCD. This converges with previous structural and metabolic findings; however, these particular changes in connectivity would not have been identified using canonical seed regions or networks. This implies the importance of FC measures in the investigation of brain pathophysiology in depression.