Ketamine-induced deficits in auditory and visual context-dependent processing in healthy volunteers: implications for models of cognitive deficits in schizophrenia

Arch Gen Psychiatry. 2000 Dec;57(12):1139-47. doi: 10.1001/archpsyc.57.12.1139.


Background: In patients with schizophrenia, deficient generation of mismatch negativity (MMN)-an event-related potential (ERP) indexing auditory sensory ("echoic") memory-and a selective increase of "context dependent" ("BX") errors in the "A-X" version of the Continuous Performance Test (AX-CPT) indicate an impaired ability to form and use transient memory traces. Animal and human studies implicate deficient N-methyl-D-aspartate receptor (NMDAR) functioning in such abnormalities. In this study, effects of the NMDAR antagonists ketamine on MMN generation and AX-CPT performance were investigated in healthy volunteers to test the hypothesis that NMDARs are critically involved in human MMN generation, and to assess the nature of ketamine-induced deficits in AX-CPT performance.

Methods: In a single-blind placebo-controlled study, 20 healthy volunteers underwent an infusion with subanesthetic doses of ketamine. The MMN-to-pitch and MMN-to-duration deviants were obtained while subjects performed an AX-CPT.

Results: Ketamine significantly decreased the peak amplitudes of the MMN-to-pitch and MMN-to-duration deviants by 27% and 21%, respectively. It induced performance deficits in the AX-CPT characterized by decreased hit rates and specific increases of errors (BX errors), reflecting a failure to form and use transient memory traces of task relevant information.

Conclusions: The NMDARs are critically involved in human MMN generation. Deficient MMN in schizophrenia thus suggests deficits in NMDAR-related neurotransmission. N-methyl-D-aspartate receptor dysfunction may also contribute to the impairment of patients with schizophrenia in forming and using transient memory traces in more complex tasks, such as the AX-CPT. Thus, NMDAR-related dysfunction may underlie deficits in transient memory at different levels of information processing in schizophrenia. Arch Gen Psychiatry. 2000;57:1139-1147.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Auditory Perception / drug effects*
  • Cognition / drug effects*
  • Cognition Disorders / chemically induced
  • Evoked Potentials / drug effects
  • Female
  • Humans
  • Ketamine / pharmacology*
  • Male
  • Memory / drug effects
  • Memory Disorders / chemically induced
  • Models, Psychological
  • Neuropsychological Tests*
  • Psychomotor Performance / drug effects
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Schizophrenia / diagnosis
  • Schizophrenia / physiopathology
  • Schizophrenic Psychology
  • Visual Perception / drug effects*


  • Receptors, N-Methyl-D-Aspartate
  • Ketamine