Ketamine normalizes brain activity during emotionally valenced attentional processing in depression

Neuroimage Clin. 2018 Jul 5;20:92-101. doi: 10.1016/j.nicl.2018.07.006. eCollection 2018.


Background: An urgent need exists for faster-acting pharmacological treatments in major depressive disorder (MDD). The glutamatergic modulator ketamine has been shown to have rapid antidepressant effects, but much remains unknown about its mechanism of action. Functional MRI (fMRI) can be used to investigate how ketamine impacts brain activity during cognitive and emotional processing.

Methods: This double-blind, placebo-controlled, crossover study of 33 unmedicated participants with MDD and 26 healthy controls (HCs) examined how ketamine affected fMRI activation during an attentional bias dot probe task with emotional face stimuli across multiple time points. A whole brain analysis was conducted to find regions with differential activation associated with group, drug session, or dot probe task-specific factors (emotional valence and congruency of stimuli).

Results: A drug session by group interaction was observed in several brain regions, such that ketamine had opposite effects on brain activation in MDD versus HC participants. Additionally, there was a similar finding related to emotional valence (a drug session by group by emotion interaction) in a large cluster in the anterior cingulate and medial frontal cortex.

Conclusions: The findings show a pattern of brain activity in MDD participants following ketamine infusion that is similar to activity observed in HCs after placebo. This suggests that ketamine may act as an antidepressant by normalizing brain function during emotionally valenced attentional processing.

Clinical trial: NCT#00088699:

Keywords: Attentional processing; Depression; Dot probe; Emotion; Functional magnetic resonance imaging (fMRI); Ketamine.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use
  • Attention / drug effects*
  • Attention / physiology
  • Brain / diagnostic imaging*
  • Brain / drug effects*
  • Brain / physiology
  • Cross-Over Studies
  • Depressive Disorder, Major / diagnostic imaging*
  • Depressive Disorder, Major / drug therapy
  • Double-Blind Method
  • Emotions / drug effects*
  • Emotions / physiology
  • Female
  • Humans
  • Ketamine / pharmacology*
  • Ketamine / therapeutic use
  • Longitudinal Studies
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Photic Stimulation
  • Young Adult


  • Antidepressive Agents
  • Ketamine

Associated data