Aberrant default-mode network-hippocampus connectivity after sad memory-recall in remitted-depression.

Rumination and cognitive reactivity (dysfunctional cognitions after sad mood-induction) remain high in remitted Major Depressive Disorder (MDD) and can contribute to new episodes. These factors have been linked to increased fMRI resting-state functional-connectivity within the Default-Mode Network (DMN). It remains unclear whether (I) increased DMN-connectivity persists during MDD-remission, and (II) whether sad mood-induction differentially affects DMN-connectivity in remitted-MDD vs controls. Moreover, DMN-connectivity studies in remitted-MDD were previously confounded by antidepressant-use. Sixty-two MDD-patients remitted from ≥2 episodes, psychotropic-medication free, and 41 controls, participated in two 5-min neutral and sad mood-inductions by autobiographical-recall and neutral/sad music, each followed by 8-min resting-state fMRI-scanning. We identified DMN-components using Independent Component Analysis and entered subject- and sessions-specific components into a repeated measures analysis of variance. Connectivity-differences were extracted and correlated with baseline cognitive reactivity and rumination as measures of vulnerability for recurrence. After sad vs neutral mood-induction, controls, but not remitted-MDD, showed an increase in connectivity between the posterior-DMN and a cluster consisting mostly of the hippocampus (P = 0.006). Less posterior-DMN-hippocampal connectivity was associated with higher cognitive reactivity (r = -0.21, P = 0.046) and rumination (r = -0.27, P = 0.017). After recalling sad autobiographical-memories, aberrant posterior-DMN-hippocampal connectivity, associated with cognitive reactivity and rumination, remains a neural vulnerability in MDD-remission.

Figueroa CA ，Mocking RJT ，van Wingen G ，Martens S ，Ruhé HG ，Schene AH ... -  《-》

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

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.

Figueroa CA ，Cabral J ，Mocking RJT ，Rapuano KM ，van Hartevelt TJ ，Deco G ，Expert P ，Schene AH ，Kringelbach ML ，Ruhé HG ... -  《-》

Negative Autobiographical Memory in Depression Reflects Elevated Amygdala-Hippocampal Reactivity and Hippocampally Associated Emotion Regulation.

Dysregulated autobiographical recall is observed in major depressive disorder (MDD). However, it is unknown whether people with MDD show abnormalities in memory-, emotion-, and control-related brain systems during reactivity to and regulation of negative autobiographical memories. We used functional magnetic resonance imaging to identify neural mechanisms underlying MDD-related emotional responses to negative autobiographical memories and the ability to downregulate these responses using a cognitive regulatory strategy known as reappraisal. We compared currently depressed, medication-free patients with MDD (n = 29) with control participants with no history of depression (n = 23). Relative to healthy control participants, medication-free MDD patients reported greater negative emotion during recall but relatively intact downregulation success. They also showed elevated amygdala activity and greater amygdala-hippocampal connectivity. This connectivity mediated the effect of MDD on negative emotional experience. When reappraising memories (vs. recalling from an immersed perspective), the MDD and control groups showed comparable recruitment of the prefrontal, parietal, and temporal cortices, and comparable downregulation of the amygdala and anterior hippocampus. However, MDD patients showed greater downregulation of the posterior hippocampus, and the extent of this downregulation predicted successful reduction of negative affect in MDD patients only. These data suggest amygdala-hippocampal connectivity and posterior hippocampal downregulation as brain mechanisms related to elevated emotional reactivity and atypical emotion regulation in MDD.

Doré BP ，Rodrik O ，Boccagno C ，Hubbard A ，Weber J ，Stanley B ，Oquendo MA ，Miller JM ，Sublette ME ，Mann JJ ，Ochsner KN ... -  《-》

The alteration of cognitive function networks in remitted patients with major depressive disorder: an independent component analysis.

Dysfunctional connectivity of resting-state functional networks has been observed in patients with major depressive disorder (MDD), particularly in cognitive function networks including the central executive network (CEN), default mode network (DMN) and salience network (SN). Findings from studies examining how aberrant functional connectivity (FC) changed after antidepressant treatment, however, have been inconsistent. Thus, the purpose of the present study was to explore potential mechanisms of altered cognitive function networks during resting-state between remitted major depressive disorder (rMDD) patients and healthy controls (HCs) and furthermore, the relationship between dysfunctional connectivity patterns in rMDD and clinical symptoms. In this study, 19 HCs and 19 rMDD patients were recruited for resting-state functional magnetic resonance imaging (fMRI) scanning. FC was evaluated with independent component analysis for CEN, DMN and SN. Two sample t tests were conducted to compare differences between rMDD and HCs. A Pearson correlation analysis was also performed to examine the relationship between connectivity of networks and cognitive function scores and clinical symptoms. Compared to healthy controls, remitted patients showed lower connectivity in CEN, mostly in the superior frontal gyrus (SFG), middle frontal gyrus (MFG), inferior parietal lobule (IPL) and part of the supramarginal gyrus (SMG). Conversely, the bilateral insula, part of the SMG (a key node of the CEN) and dorsal anterior cingulate cortex (dACC) of the DMN showed higher connectivity in rMDD patients. Pearson correlation results demonstrated that connectivity of the right IPL in CEN was positively correlated with cognitive function scores, and connectivity of the left insula was negatively correlated with BDI scores. Though rMDD patients reached the standard of clinal remission, unique impairments of FC in cognitive function networks remained. Aberrant FC between cognitive function networks responsible for executive control was observed in rMDD and may be associated with residual clinical symptoms.

Liu G ，Jiao K ，Zhong Y ，Hao Z ，Wang C ，Xu H ，Teng C ，Song X ，Xiao C ，Fox PT ，Zhang N ，Wang C ... -  《-》

Recalling happy memories in remitted depression: a neuroimaging investigation of the repair of sad mood.

Foland-Ross LC ，Cooney RE ，Joormann J ，Henry ML ，Gotlib IH ... -  《-》