Altered Emotional Interference Processing in Affective and Cognitive-Control Brain Circuitry in Major Depression

Christina L. Fales, Deanna M. Barch, Melissa M. Rundle, Mark A. Mintun, Abraham Z. Snyder, Jonathan D. Cohen, Jose Mathews, Yvette I. Sheline

Research output: Contribution to journalArticlepeer-review

410 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)377-384
Number of pages8
JournalBiological Psychiatry
Issue number4
StatePublished - Feb 15 2008

All Science Journal Classification (ASJC) codes

  • Biological Psychiatry


  • Affective control
  • amygdala
  • cognitive control
  • depression
  • dorsolateral prefrontal cortex
  • emotion
  • emotional interference


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