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

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.

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

“…We found that the entropy associated with the FN-DMN-Str-SN state was significantly decreased in patients in neutral mood. This indicates a higher predictability of occurrence (Wang, 2008) of this FC state in rrMDD patients, supporting the idea that this brain state occurs in a less flexible manner.…”

“…Interestingly, previous studies in MDD have also found increased dynamic FC in areas overlapping with the FN‐DMN‐Str‐SN state: between the frontoparietal network and DMN (Kaiser et al, ) within the DMN (Wise et al, ) and between DMN (MPFC) and the insula (Kaiser et al, ); related to levels of self‐report rumination (Kaiser et al, ). This suggests that dynamic changes in FC in these areas might be particularly important for depression and a ruminative thinking style.…”

“…dFC changes during tasks (Sakoglu et al, ) and resting‐state (Damaraju et al, ; Jin et al, ; Kaiser et al, ) have been associated with psychiatric disorders and with reduced behavioral/cognitive performance in healthy subjects (Cabral, Vidaurre, et al, ; Jia, Hu, & Deshpande, ; Madhyastha, Askren, Boord, & Grabowski, ). For MDD specifically, findings from recent studies suggest aberrations in dFC involving DMN, (Wise et al, ) frontal, and SN areas (Demirtaş et al, ; Kaiser et al, ). However, it remains unclear whether this persists during MDD remission.…”

Reduced Default Mode Network Functional Connectivity in Patients with Recurrent Major Depressive Disorder

“…comparisons. An early MDD study (7) found that DMN FC was positively correlated with current episode duration but this was not confirmed subsequently (9,25). We conclude that illness duration is likely unrelated to DMN FC.…”

Conservative and disruptive modes of adolescent change in brain functional connectivity

“…We have found that trajectories of intra-cortical myelination in fronto-striatal systems are related to individual differences in compulsivity and impulsivity (Ziegler et al, 2018). It is also noteworthy that both the default mode network (Wise et al, 2017) and cortico-subcortical connectivity (Heller, 2016) have been previously implicated in the pathophysiology of major depressive disorder.…”