title: N-methyl-d-aspartate receptor antagonist ketamine impairs action-monitoring activity in the prefrontal cortex.
abstract: Failures in monitoring of self-generated actions are thought to underlie the positive symptoms in schizophrenia. It has been hypothesized that these deficits may be caused by a dysfunction of N-methyl-d-aspartate receptors (NMDARs). Here we recorded the activity of prefrontal neurons in monkeys performing an antisaccade task, while we administered a subanesthetic dose of the noncompetitive NMDAR antagonist ketamine. Many neurons discriminated between correct antisaccades and response errors in their postresponse activity. Ketamine increased the activity for the neurons' nonpreferred response, thereby decreasing the neurons' performance selectivity. Ketamine also affected the monkeys' behavior after an error, consistent with a deficit in error detection. The results show that NMDARs play an important role in action monitoring in primates. The decrease in performance selectivity of prefrontal neurons after ketamine can help to explain the deficits in action monitoring found in humans after ketamine administration and provides support for the hypothesis that an NMDAR dysfunction underlies self-monitoring deficits and psychotic symptoms in schizophrenia.
authors.affiliation: University of Western Ontario.
authors.forename: Kevin
authors.initials: K
authors.lastname: Skoblenick
authors.forename: Stefan
authors.initials: S
authors.lastname: Everling
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004192:Discrimination, Psychological / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D056344:Executive Function / Q000187:drug effects / Q000502:physiology; D007649:Ketamine / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D011597:Psychomotor Performance / Q000187:drug effects* / Q000502:physiology; D012372:ROC Curve; D011930:Reaction Time / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012438:Saccades / Q000187:drug effects / Q000502:physiology; D013647:Task Performance and Analysis; D013997:Time Factors
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine