Inflexibly sustained negative affect and rumination independently link default mode network efficiency to subclinical depressive symptoms.

Aberrant DMN connectivity and activity have been robustly linked to Major Depressive Disorder (MDD) and risk for depression. This link has mostly been explained in terms of rumination, a form of negative, repetitive cognitive processing. Yet, accumulating findings are indicating altered DMN dynamics during emotional processing in MDD, pointing at a potential emotion-related DMN pathology in depression linked to inflexibly sustained emotional responses. Such a link might be especially important in understanding risk of depression. However, whether inflexible emotional processing (i.e. emotional inertia) is connecting aberrant DMN organization to risk of depression as well as how this might relate to rumination remains unclear. Addressing this gap, 34 participants underwent a resting-state fMRI and a 7-day Experience Sampling phase. Using regression and multiple mediation analysis we investigated the relations between negative emotional inertia, rumination, DMN organization and risk of depression as indicated by high subclinical depressive symptoms. The findings indicated that DMN efficiency at rest was positively associated with depressive symptoms and risk of depression. Both negative emotional inertia in daily life and rumination were independently mediating this relationship. While negative emotional inertia was connected to a broad increase in the coupling of DMN regions, rumination was only related to an increase in node strength of the dorsomedial Prefrontal Cortex. These findings are pointing towards an emotional-related DMN pathology contributing to risk of depression. Furthermore the findings are indicating that this relationship is independent from the rumination-related link between the DMN and depression - representing different aspects of DMN organization.

Mood congruency effects are mediated by shifts in salience and central executive network efficiency.

Emotions are not confined to short momentary states but carry on over time, facilitating the perception and interpretation of the environment in mood-congruent ways. Yet, the (neural) mechanism linking affective stimulation at a certain time-point to such altered, mood-congruent processing of stimuli presented at a subsequent time-point remains unknown. Recent research suggests that such a link could be explained by transient effects of affective stimulation on the organization of intrinsic macro-scale neural networks. It remains, however, unclear whether these changes in network organization are influencing subsequent perception in a mood-congruent way. Addressing this gap the current study investigated whether changes in network organization, measured in terms of network efficiency, mediate the relation between mood induction and mood-congruent processing as measured by reaction times during an emotional Stroop task. The results demonstrated that negative mood induction increased the efficiency of the salience network and decreased the efficiency of the central executive network. This modulation of network efficiency fully mediated the effects of mood induction on reaction times to negative words. These findings indicate that transient shifts in the organization of macro-scale neural networks are an essential part of the emotional response and can help to explain how affect shapes our interaction with the environment.

Prefrontal networks dynamically related to recovery from major depressive disorder: a longitudinal pharmacological fMRI study.

Due to lacking predictors of depression recovery, successful treatment of major depressive disorder (MDD) is frequently only achieved after therapeutic optimization leading to a prolonged suffering of patients. This study aimed to determine neural prognostic predictors identifying non-remitters prior or early after treatment initiation. Moreover, it intended to detect time-sensitive neural mediators indicating depression recovery. This longitudinal, interventional, single-arm, open-label, phase IV, pharmacological functional magnetic resonance imaging (fMRI) study comprised four scans at important stages prior (day 0) and after escitalopram treatment initiation (day 1, 28, and 56). Totally, 22 treatment-free MDD patients (age mean ± SD: 31.5 ± 7.7; females: 50%) suffering from a concurrent major depressive episode without any comorbid DSM-IV axis I diagnosis completed the study protocol. Primary outcome were neural prognostic predictors of depression recovery. Enhanced de-activation of anterior medial prefrontal cortex (amPFC, single neural mediator) indicated depression recovery correlating with MADRS score and working memory improvements. Strong dorsolateral PFC (dlPFC) activation and weak dlPFC-amPFC, dlPFC-posterior cingulate cortex (PCC), dlPFC-parietal lobe (PL) coupling (three prognostic predictors) hinted at depression recovery at day 0 and 1. Preresponse prediction of continuous (dlPFC-PL: R2day1 = 55.9%, 95% CI: 22.6-79%, P < 0.005) and dichotomous (specificity/sensitivity: SP/SNday1 = 0.91/0.82) recovery definitions remained significant after leave-one-out cross-validation. Identified prefrontal neural predictors might propel the future development of fMRI markers for clinical decision making, which could lead to increased response rates and adherence during acute phase treatment periods. Moreover, this study underscores the importance of the amPFC in depression recovery.

Different Aspects of the Neural Response to Socio-Emotional Events Are Related to Instability and Inertia of Emotional Experience in Daily Life: An fMRI-ESM Study.

Emotions are fundamentally temporal processes that dynamically change over time. This temporal nature is inherently involved in making emotions adaptive by guiding interactions with our environment. Both the size of emotional changes across time (i.e., emotional instability) and the tendency of emotions to persist across time (i.e., autocorrelation of emotional experience, emotional inertia) are key features of a person's emotion dynamics, and have been found central to maladaptive functioning and psychopathology as well as linked to social functioning. However, whether different (neural) mechanisms are underlying these dynamics as well as how they are related to the processing of (socio-) emotional information is to date widely unknown. Using a combination of Experience Sampling methods (ESMs) and fMRI (involving a social feedback paradigm), we examine how emotional instability and inertia in everyday life are associated with different aspects of the neural response to socio-emotional events. The findings indicate that while emotional instability is connected to the response of the core salience network (SN), emotional inertia is associated to responses in the parahippocampal gyrus (PHG) and lateral orbitofrontal cortex (lOFC). This is the first study showing that different aspects of the neural response to socio-emotional events are associated with different aspects of the temporal dynamics of emotion in real life.