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Revisiting default mode network function in major depression: evidence for disrupted subsystem connectivity

Published online by Cambridge University Press:  31 October 2013

F. Sambataro*
Brain Center for Motor and Social Cognition, Istituto Italiano di Tecnologia@UniPR, Parma, Italy
N. D. Wolf
Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Mannheim, Germany
M. Pennuto
Dulbecco Telethon Institute Laboratory of Neurodegenerative Diseases, Centre for Integrative Biology, University of Trento, Trento, Italy
N. Vasic
Department of Psychiatry and Psychotherapy III, University of Ulm, Ulm, Germany
R. C. Wolf*
Center of Psychosocial Medicine, Department of General Psychiatry, University of Heidelberg, Germany
*Address for correspondence: F. Sambataro M.D., Ph.D., Brain Center for Motor and Social Cognition, Istituto Italiano di Tecnologia@UniPR, Via Università 12, Parma, Italy. (Email:



Major depressive disorder (MDD) is characterized by alterations in brain function that are identifiable also during the brain's ‘resting state’. One functional network that is disrupted in this disorder is the default mode network (DMN), a set of large-scale connected brain regions that oscillate with low-frequency fluctuations and are more active during rest relative to a goal-directed task. Recent studies support the idea that the DMN is not a unitary system, but rather is composed of smaller and distinct functional subsystems that interact with each other. The functional relevance of these subsystems in depression, however, is unclear.


Here, we investigated the functional connectivity of distinct DMN subsystems and their interplay in depression using resting-state functional magnetic resonance imaging.


We show that patients with MDD exhibit increased within-network connectivity in posterior, ventral and core DMN subsystems along with reduced interplay from the anterior to the ventral DMN subsystems.


These data suggest that MDD is characterized by alterations of subsystems within the DMN as well as of their interactions. Our findings highlight a critical role of DMN circuitry in the pathophysiology of MDD, thus suggesting these subsystems as potential therapeutic targets.

Original Articles
Copyright © Cambridge University Press 2013 

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