Ketamine effects on brain function--simultaneous fMRI/EEG during a visual oddball task

Neuroimage. 2011 Sep 15;58(2):508-25. doi: 10.1016/j.neuroimage.2011.06.045. Epub 2011 Jun 29.


Background: Behavioral and electrophysiological human ketamine models of schizophrenia are used for testing compounds that target the glutamatergic system. However, corresponding functional neuroimaging models are difficult to reconcile with functional imaging and electrophysiological findings in schizophrenia. Resolving the discrepancies between different observational levels is critical to understand the complex pharmacological ketamine action and its usefulness for modeling schizophrenia pathophysiology.

Methods: We conducted a within-subject, randomized, placebo-controlled pharmacoimaging study in twenty-four male volunteers. Subjects were given low-dose S-ketamine (bolus prior to functional imaging: 0.1mg/kg during 5min, thereafter continuous infusion: 0.015625mg/kg/min reduced by 10% every ten minutes) or placebo while performing a visual oddball task during simultaneous functional magnetic resonance imaging (fMRI) with continuous recording of event-related potentials (P300) and electrodermal activity (EDA). Before and after intervention, psychopathological status was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Altered State of Consciousness (5D-ASC) Rating Scale.

Results: P300 amplitude and corresponding BOLD responses were diminished in the ketamine condition in cortical regions being involved in sensory processing/selective attention. In both measurement modalities separation of drug conditions was achieved with area under the curve (AUC) values of up to 0.8-0.9. Ketamine effects were also observed in the clinical, behavioral and peripheral physiological domains (Positive and Negative Syndrome Scale, reaction hit and false alarm rate, electrodermal activity and heart rate) which were in part related to the P300/fMRI measures.

Conclusion: The findings from our ketamine experiment are consistent across modalities and directly related to observations in schizophrenia supporting the validity of the model. Our investigation provides the first prototypic example of a pharmacoimaging study using simultaneously acquired fMRI/EEG.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation
  • Adult
  • Analysis of Variance
  • Brain / drug effects*
  • Cross-Over Studies
  • Data Interpretation, Statistical
  • Double-Blind Method
  • Electroencephalography
  • Event-Related Potentials, P300 / drug effects
  • Evoked Potentials, Auditory / physiology
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Female
  • Functional Laterality / drug effects
  • Functional Laterality / physiology
  • Galvanic Skin Response / drug effects
  • Humans
  • Image Processing, Computer-Assisted
  • Ketamine / pharmacology*
  • Magnetic Resonance Imaging
  • Male
  • Oxygen / blood
  • Psychomotor Performance / drug effects*
  • Visual Perception / drug effects*
  • Young Adult


  • Excitatory Amino Acid Antagonists
  • Ketamine
  • Oxygen