Edited by Marcus E. Raichle, Washington University, St. Louis, MO, and approved April 28, 2010 (received for review January 12, 2010)
To better understand intrinsic brain connections in major depression, we used a neuroimaging technique that measures resting state functional connectivity using functional MRI (fMRI). Three different brain networks—the cognitive control network, default mode network, and affective network—were investigated. Compared with controls, in depressed subjects each of these three networks had increased connectivity to the same bilateral dorsal medial prefrontal cortex region, an area that we term the dorsal nexus. The dorsal nexus demonstrated dramatically increased depression-associated fMRI connectivity with large portions of each of the three networks. The discovery that these regions are linked together through the dorsal nexus provides a potential mechanism to explain how symptoms of major depression thought to arise in distinct networks—decreased ability to focus on cognitive tasks, rumination, excessive self-focus, increased vigilance, and emotional, visceral, and autonomic dysregulation—could occur concurrently and behave synergistically. It suggests that the newly identified dorsal nexus plays a critical role in depressive symptomatology, in effect “hot wiring” networks together; it further suggests that reducing increased connectivity of the dorsal nexus presents a potential therapeutic target.
Author contributions: Y.I.S. and M.A.M. designed research; Y.I.S. and Z.Y. performed research; Y.I.S. and Z.Y. analyzed data; and Y.I.S., J.L.P., and M.A.M. wrote the paper.
Conflict of interest statement: Y.I.S. has served on the advisory board and speakers’ bureau of Eli Lilly, Inc. M.A.M. serves as a consultant for Avid Radiopharmaceuticals. Y.I.S. is independent of any commercial provider, had full access to all of the data in this study, and takes responsibility for the integrity of the data and the accuracy of the data analysis. No author named on the title page of this study has any financial interest in the results of the study or any other conflict of interest relevant to the subject matter of this manuscript.
This article is a PNAS Direct Submission.
Freely available online through the PNAS open access option.
