Reduced global functional connectivity of the medial prefrontal cortex in major depressive disorder

Abstract

Background: Major depressive disorder is a disabling neuropsychiatric condition that is associated with disrupted functional connectivity across brain networks. The precise nature of altered connectivity, however, remains incompletely understood. The current study was designed to examine the coherence of large-scale connectivity in depression using a recently developed technique termed global brain connectivity.

Methods: A total of 82 subjects, including medication-free patients with major depression (n = 57) and healthy volunteers (n = 25) underwent functional magnetic resonance imaging with resting data acquisition for functional connectivity analysis. Global brain connectivity was computed as the mean of each voxel's time series correlation with every other voxel and compared between study groups. Relationships between global connectivity and depressive symptom severity measured using the Montgomery-Åsberg Depression Rating Scale were examined by means of linear correlation.

Results: Relative to the healthy group, patients with depression evidenced reduced global connectivity bilaterally within multiple regions of medial and lateral prefrontal cortex. The largest between-group difference was observed within the right subgenual anterior cingulate cortex, extending into ventromedial prefrontal cortex bilaterally (Hedges' g = -1.48, P < 0.000001). Within the depressed group, patients with the lowest connectivity evidenced the highest symptom severity within ventromedial prefrontal cortex (r = -0.47, P = 0.0005).

Conclusions: Patients with major depressive evidenced abnormal large-scale functional coherence in the brain that was centered within the subgenual cingulate cortex, and medial prefrontal cortex more broadly. These data extend prior studies of connectivity in depression and demonstrate that functional disconnection of the medial prefrontal cortex is a key pathological feature of the disorder. Hum Brain Mapp 37:3214-3223, 2016. © 2016 Wiley Periodicals, Inc.

Keywords: depression; functional connectivity; neuroimaging; prefrontal cortex; resting state; subgenual anterior cingulate cortex.

Figure 1

Reduced global brain connectivity in major depressive disorder. (A) Clusters where MDD patients showed significantly less GBC compared to healthy volunteers. (B) Histogram of GBC reduction in major depressive disorder relative to healthy volunteers across all voxels showing significant group differences. (C) Zoomed in view of clusters of significant dysconnectivity in major depressive disorder relative to healthy volunteers within the medial prefrontal cortex and subgenual anterior cingulate. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 2

Increased global brain connectivity in major depressive disorder. (A) Significantly increased GBC in major depressive disorder compared to healthy volunteers within the posterior cerebellum. (B) Significantly increased GBC in major depressive disorder compared to healthy volunteers within the left extrastriate visual cortex. (C) Histogram of GBC increases in major depressive disorder relative to healthy volunteers across all voxels showing significant group differences. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 3

Global brain connectivity within the ventromedial prefrontal cortex in major depressive disorder and association with symptom severity. (A) Cluster depicts significantly reduced GBC in major depressive disorder patients relative to healthy volunteers within an anatomically defined bilateral VMPFC. (B) Inverse linear correlation between GBC within the VMPFC and depressive severity as measured by Montgomery‐Åsberg Depression Rating Scale score. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]