Ketamine alters neural processing of facial emotion recognition in healthy men: an fMRI study

Neuroreport. 2003 Mar 3;14(3):387-91. doi: 10.1097/00001756-200303030-00018.


Disruption of facial emotion perception occurs in neuropsychiatric disorders where the expression of emotion is dulled or blunted, for example depersonalization disorder and schizophrenia. It has been suggested that, in the clinical context of emotional blunting, there is a shift in the relative contribution of brain regions subserving cognitive and emotional processing. The non-competitive glutamate receptor antagonist ketamine produces such emotional blunting in healthy subjects. Therefore, we hypothesised that in healthy subjects ketamine would elicit neural responses to emotional stimuli which mimicked those reported in depersonalization disorder and schizophrenia. Thus, we predicted that ketamine would produce reduced activity in limbic and visual brain regions involved in emotion processing, and increased activity in dorsal regions of the prefrontal cortex and cingulate gyrus, both associated with cognitive processing and, putatively, with emotion regulation. Measuring BOLD signal change in fMRI, we examined the neural correlates of ketamine-induced emotional blunting in eight young right-handed healthy men receiving an infusion of ketamine or saline placebo while viewing alternating 30 s blocks of faces displaying fear versus neutral expressions. The normal pattern of neural response occurred in limbic and visual cortex to fearful faces during the placebo infusion. Ketamine abolished this: significant BOLD signal change was demonstrated only in left visual cortex. However, with ketamine, neural responses were demonstrated to neutral expressions in visual cortex, cerebellum and left posterior cingulate gyrus. Emotional blunting may be associated with reduced limbic responses to emotional stimuli and a relative increase in the visual cortical response to neutral stimuli.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain Mapping
  • Cerebrovascular Circulation
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Facial Expression*
  • Fear*
  • Humans
  • Ketamine / pharmacology*
  • Limbic System / physiology*
  • Magnetic Resonance Imaging
  • Male
  • Mental Processes / drug effects
  • Mental Processes / physiology
  • Oxygen / blood
  • Reference Values
  • Visual Cortex / drug effects
  • Visual Cortex / physiology*


  • Excitatory Amino Acid Antagonists
  • Ketamine
  • Oxygen