Send to

Choose Destination
Hum Brain Mapp. 2019 Mar 12. doi: 10.1002/hbm.24559. [Epub ahead of print]

Altered ability to access a clinically relevant control network in patients remitted from major depressive disorder.

Figueroa CA1,2,3, Cabral J4,5,6, Mocking RJT1,2, Rapuano KM7, van Hartevelt TJ4, Deco G8,9,10,11, Expert P12,13, Schene AH1,14,15, Kringelbach ML4,5,6, Ruhé HG1,4,14,15.

Author information

Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Brain Imaging Center, Academic Medical Center, Amsterdam, The Netherlands.
School of Social Welfare, University of California Berkeley, Berkeley, California.
Department of Psychiatry, University of Oxford, Oxford, United Kingdom.
Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
Center for Music in the Brain, Aarhus University, Aarhus, Denmark.
Department of Psychological and Brain Sciences, Dartmouth College, Hanover, New Hampshire.
Center for Brain and Cognition, Computational Neuroscience Group, Department of Information and Communication Technologies, Universitat Pompeu Fabra, Barcelona, Spain.
Institució Catalana de la Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
Department of Neuropsychology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
School of Psychological Sciences, Monash University, Melbourne, Australia.
Centre for Mathematics of Precision Healthcare, Imperial College London, London, United Kingdom.
Department of Mathematics, Imperial College London, London, United Kingdom.
Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands.
Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands.


Neurobiological models to explain vulnerability of major depressive disorder (MDD) are scarce and previous functional magnetic resonance imaging studies mostly examined "static" functional connectivity (FC). Knowing that FC constantly evolves over time, it becomes important to assess how FC dynamically differs in remitted-MDD patients vulnerable for new depressive episodes. Using a recently developed method to examine dynamic FC, we characterized re-emerging FC states during rest in 51 antidepressant-free MDD patients at high risk of recurrence (≥2 previous episodes), and 35 healthy controls. We examined differences in occurrence, duration, and switching profiles of FC states after neutral and sad mood induction. Remitted MDD patients showed a decreased probability of an FC state (p < 0.005) consisting of an extensive network connecting frontal areas-important for cognitive control-with default mode network, striatum, and salience areas, involved in emotional and self-referential processing. Even when this FC state was observed in patients, it lasted shorter (p < 0.005) and was less likely to switch to a smaller prefrontal-striatum network (p < 0.005). Differences between patients and controls decreased after sad mood induction. Further, the duration of this FC state increased in remitted patients after sad mood induction but not in controls (p < 0.05). Our findings suggest reduced ability of remitted-MDD patients, in neutral mood, to access a clinically relevant control network involved in the interplay between externally and internally oriented attention. When recovering from sad mood, remitted recurrent MDD appears to employ a compensatory mechanism to access this FC state. This study provides a novel neurobiological profile of MDD vulnerability.


cognitive control; dynamic FC; functional networks; major depressive disorder; resting-state fMRI


Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center