Altered Effective Connectivity within the Fronto-Limbic Circuitry in Response to Negative Emotional Task in Female Patients with Major Depressive Disorder

Abstract

Background: Major depressive disorder (MDD) is a mood disorder associated with disruptions in emotional control. Previous studies have investigated abnormal regional activity and connectivity within the fronto-limbic circuit. However, condition-specific connectivity changes and their association with the pathophysiology of MDD remain unexplored. This study investigated effective connectivity in the fronto-limbic circuit induced by negative emotional processing from patients with MDD. Methods: Thirty-four unmedicated female patients with MDD and 28 healthy participants underwent event-related functional magnetic resonance imaging at 7T while viewing emotionally negative and neutral images. Brain regions whose dynamics are driven by experimental conditions were identified by using statistical parametric mapping. Effective connectivity among regions of interest was then estimated by using dynamic causal modeling. Results: Patients with MDD had lower activation of the orbitofrontal cortex (OFC) and higher activation of the parahippocampal gyrus (PHG) than healthy controls (HC). In association with these regional changes, we found that patients with MDD did not have significant modulatory connections from the primary visual cortex (V1) to OFC, whereas those connections of HC were significantly positively modulated during negative emotional processing. Regarding the PHG activity, patients with MDD had greater modulatory connection from the V1, but reduced negative modulatory connection from the OFC, compared with healthy participants. Conclusions: These results imply that disrupted effective connectivity among regions of the OFC, PHG, and V1 may be closely associated with the impaired regulation of negative emotional processing in the female patients with MDD.

Effective connectivity during faces processing in major depression – distinguishing markers of pathology, risk, and resilience

“…MDD patients with higher negative affect also exerted less inhibitory influence from left dorsolateral prefrontal cortex to right fusiform gyrus. These results are compatible with previous studies reporting decreased functional connectivity between frontal and visual regions in MDD patients during an emotional task (65)(66) and at resting-state (67)(68)(69). The lateral prefrontal cortex plays an important role in the integration of cognitive and emotional information (70)(71) and inhibition of task-irrelevant stimuli (72)(73)(74).…”

Networks underpinning emotion: A systematic review and synthesis of functional and effective connectivity

“…Additionally, only one study provided a justification for their sample size ( Payer et al., 2012 ). Eleven studies did not apply statistical corrections for multiple comparisons ( Banks et al., 2007 ; Das et al., 2005 ; de Marco et al., 2006 ; Goulden et al., 2012 ; Hakamata et al., 2016 ; Jabbi and Keysers, 2008 ; Payer et al., 2012 ; Tak et al., 2021 ; Torrisi et al., 2013 ; Tschacher et al., 2010 ; Vai et al., 2015 ), with three of these not providing a justification ( de Marco et al., 2006 ; Jabbi and Keysers, 2008 ; Payer et al., 2012 ). The effect sizes calculated for the present review were typically very large across studies.…”

“…Task included behavioural valence check. Tak et al. (2021) DCM analysis ( n = 28) – SPM12 Event-related.…”

“…A further 7 studies eligible for inclusion were identified through this search ( Breakspear et al., 2015 ; Dima et al., 2015 ; Goulden et al., 2012 ; Sladky et al., 2015 ; Tak et al., 2021 ; Torrisi et al., 2013 ; Vai et al., 2015 ), and are reported in the results below.…”

Social support mediates the influence of cerebellum functional connectivity strength on postpartum depression and postpartum depression with anxiety

“…The findings of the present study show that PPD and PPD-A patients have disorder specific alterations in the FI of the brain network. This is supported by reports that ParaHipp was found with higher activation in female depressive patients than healthy controls [ 31 ], and is involved in processing negative emotional stimuli, including those related to trauma [ 32 ]. Furthermore, lesions in temporal cortex and ParaHipp, which are part of the temporal-limbic network, typically disrupt episodic memory which is common in patients with depression and cognitive impairment [ 33 ].…”