Altered emotional interference processing in affective and cognitive-control brain circuitry in major depression

Abstract

Background: Major depression is characterized by a negativity bias: an enhanced responsiveness to, and memory for, affectively negative stimuli. However, it is not yet clear whether this bias represents 1) impaired top-down cognitive control over affective responses, potentially linked to deficits in dorsolateral prefrontal cortex function; or 2) enhanced bottom-up responses to affectively laden stimuli that dysregulate cognitive control mechanisms, potentially linked to deficits in amygdala and anterior cingulate function.

Methods: We used an attentional interference task using emotional distracters to test for top-down versus bottom-up dysfunction in the interaction of cognitive-control circuitry and emotion-processing circuitry. A total of 27 patients with major depression and 24 control participants was tested. Event-related functional magnetic resonance imaging was carried out as participants directly attended to, or attempted to ignore, fear-related stimuli.

Results: Compared with control subjects, patients with depression showed an enhanced amygdala response to unattended fear-related stimuli (relative to unattended neutral). By contrast, control participants showed increased activity in right dorsolateral prefrontal cortex (Brodmann areas 46/9) when ignoring fear stimuli (relative to neutral), which the patients with depression did not show. In addition, the depressed participants failed to show evidence of error-related cognitive adjustments (increased activity in bilateral dorsolateral prefrontal cortex on posterror trials), but the control group did show them.

Conclusions: These results suggest multiple sources of dysregulation in emotional and cognitive control circuitry in depression, implicating both top-down and bottom-up dysfunction.

Figures

Figure 1

Example of a stimulus screen used in the emotional conflict task.

Figure 2

Areas in the left amygdala (a) and right dorsolateral prefrontal cortex (b) showing a significant three-way interaction of attention × emotion × group. Graphs show percent change in signal magnitude for the fear-minus-neutral contrast in each region. Error bars show standard errors of the mean.

Figure 3

Areas in left (a) and right (b) dorsolateral prefrontal cortex showing significant group differences in the post-error effect: interaction of trial-type (post-correct versus post-error) × group. Graphs show percent change in signal magnitude for each region. Error bars show standard errors of the mean.

Figure 4

Areas in the subgenual anterior cingulate (a) and superior-rostral anterior cingulate (c) show significant group differences across all conditions. Areas in pregenual cingulate (b) show significant differences in a group × attention interaction, where controls had less deactivation in the attend-to-faces conditions (left side of graph) while depressed had less deactivation in the ignore-faces conditions (right side of graph). Graphs show percent change in signal magnitude for each region. Error bars show standard errors of the mean.