Instability of default mode network connectivity in major depression: a two-sample confirmation study

A H Young,L Marwood,T Wise,W-M Luh,A J Cleare,S C R Williams,D J Lythgoe,A M Perkins,A Herane-Vives,R Joules,D Arnone

doi:10.1038/tp.2017.40

Abstract

Major depression is associated with altered static functional connectivity in various brain networks, particularly the default mode network (DMN). Dynamic functional connectivity is a novel tool with little application in affective disorders to date, and holds the potential to unravel fluctuations in connectivity strength over time in major depression. We assessed stability of connectivity in major depression between the medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC), key nodes in the DMN that are implicated in ruminative cognitions. Functional connectivity stability between the mPFC and PCC over the course of a resting-state functional magnetic resonance imaging (fMRI) scan was compared between medication-free patients with major depression and healthy controls matched for age, sex and handedness. We tested replicability of the results in an independent sample using multi-echo resting-state fMRI. The primary sample included 20 patients and 19 controls, while the validation sample included 19 patients and 19 controls. Greater connectivity variability was detected in major depression between mPFC and PCC. This was demonstrated in both samples indicating that the results were reliable and were not influenced by the fMRI acquisition approach used. Our results demonstrate that alterations within the DMN in major depression go beyond changes in connectivity strength and extend to reduced connectivity stability within key DMN regions. Findings were robustly replicated across two independent samples. Further research is necessary to better understand the nature of these fluctuations in connectivity and their relationship to the aetiology of major depression.

Highlights

Depression is a common illness with substantial negative consequences for sufferers and society.[1,2] A better insight into neurobiological changes contributing to symptom generation is a research priority to improve diagnosis and treatment.[3]Neuroimaging has enhanced our understanding of the neurobiological mechanisms underlying depressive symptoms[3,4,5,6] by identifying potential alterations in the structural and functional brain networks.[4,7] The default mode network (DMN) is one system that has attracted great research interest in major depression
Heightened static functional connectivity has been shown in major depression within this subsystem in association with a ruminative cognitive style,[4,10] there is uncertainty about its functional temporal stability
This study showed increased variability in connectivity within the DMN between the medial prefrontal cortex (mPFC) and the insula, which correlated with a ruminative thinking style and coexisted with decreased variability between the mPFC and the parahippocampal gyrus.[13]

Summary

INTRODUCTION

Depression is a common illness with substantial negative consequences for sufferers and society.[1,2] A better insight into neurobiological changes contributing to symptom generation is a research priority to improve diagnosis and treatment.[3]. We evaluated temporal connectivity variability between the mPFC and the PCC, a subsystem within the DMN, given its relevance to ruminative cognitions associated with depression.[8,9] Kaiser et al.[13] observed increased connectivity variability between the mPFC and insula, part of the ‘salience network’ that is known to influence synergistically this DMN subsystem when processing internally generated salient information,[14] correlating with levels of rumination. Multi-echo data were preprocessed using the multi-echo independent component analysis tool in AFNI15 to isolate components in the signal representing true blood oxygen level dependent (BOLD) signal This was used in place of RETROICOR as it has been shown to be a more effective method of de-noising.[15] The remaining processing steps were identical for both samples for consistency.

Participants

DISCUSSION

CONFLICT OF INTEREST