Altered emotional interference processing in affective and cognitive-control brain circuitry in major depression.
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.
Fales
Christina L
CL
Department of Psychology, Washington University in St. Louis, St. Louis, Missouri 63110, USA.
Barch
Deanna M
DM
Rundle
Melissa M
MM
Mintun
Mark A
MA
Snyder
Abraham Z
AZ
Cohen
Jonathan D
JD
Mathews
Jose
J
Sheline
Yvette I
YI
D000328:Adult; D000339:Affect; D000679:Amygdala / Q000503:physiopathology; D001288:Attention; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000175:diagnosis / Q000453:epidemiology; D003865:Major Depressive Disorder / Q000453:epidemiology / Q000503:physiopathology*; D005145:Face; D005239:Fear; D005260:Female; D006179:Gyrus Cinguli / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000503:physiopathology*; D009483:Neuropsychological Tests; D011795:Surveys and Questionnaires; D014796:Visual Perception
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