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Modeling a negative response bias in the human amygdala by noradrenergic-glucocorticoid interactions.

An emerging theme in the neuroscience of emotion is the question of how acute stress shapes, and distorts, social-emotional behavior. The prevailing neurocircuitry models of social-emotional behavior emphasize the central role of the amygdala. Acute stress leads to increased central levels of norepinephrine (NE) and cortisol (CORT), and evidence suggests that these endogenous neuromodulators synergistically influence amygdala responses to social-emotional stimuli. We therefore hypothesized that amygdala responses to emotional facial expressions would be susceptible to pharmacologically induced increases in central NE and CORT levels. To specifically test this hypothesis, we measured amygdala activation to emotional faces using functional magnetic resonance imaging in 62 healthy subjects under four pharmacological conditions: (1) single oral dose of placebo, (2) 4 mg of the selective NE-reuptake inhibitor reboxetine (RBX), (3) 30 mg of hydrocortisone, or (4) both drugs in combination. We found that a decrease in amygdala activation to positive facial emotion was coupled with an increase in amygdala activation to negative facial emotion in the RBX-CORT combined challenge condition. In conclusion, a pharmacologically induced elevation of central NE and CORT levels in healthy subjects created a negative response bias in the amygdala that did not exist at baseline. Our results implicate a causative role of NE-CORT interactions in the emergence of a negative bias of cognitive and emotional functions which is germane in stress-related affective spectrum disorders.

Pubmed ID: 19036981


  • Kukolja J
  • Schläpfer TE
  • Keysers C
  • Klingmüller D
  • Maier W
  • Fink GR
  • Hurlemann R


The Journal of neuroscience : the official journal of the Society for Neuroscience

Publication Data

November 26, 2008

Associated Grants


Mesh Terms

  • Adrenergic Uptake Inhibitors
  • Adult
  • Amygdala
  • Bias (Epidemiology)
  • Brain Mapping
  • Emotions
  • Facial Expression
  • Female
  • Glucocorticoids
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mood Disorders
  • Morpholines
  • Neuropsychological Tests
  • Norepinephrine
  • Photic Stimulation
  • Recognition (Psychology)
  • Stress, Psychological
  • Synaptic Transmission
  • Young Adult