Effects of ketamine on brain function during response inhibition
The uncompetitive N-methyl-D-aspartate (NMDA) receptor (NMDAR) antagonist ketamine has been proposed to model symptoms of psychosis. Inhibitory deficits in the schizophrenia spectrum have been reliably reported using the antisaccade task. Interestingly, although similar antisaccade deficits have been reported following ketamine in non-human primates, ketamine-induced deficits have not been observed in healthy human volunteers.
To investigate the effects of ketamine on brain function during an antisaccade task, we conducted a double-blind, placebo-controlled, within-subjects study on n = 15 healthy males. We measured the blood oxygen level dependent (BOLD) response and eye movements during a mixed antisaccade/prosaccade task while participants received a subanesthetic dose of intravenous ketamine (target plasma level 100 ng/ml) on one occasion and placebo on the other occasion.
While ketamine significantly increased self-ratings of psychosis-like experiences, it did not induce antisaccade or prosaccade performance deficits. At the level of BOLD, we observed an interaction between treatment and task condition in somatosensory cortex, suggesting recruitment of additional neural resources in the antisaccade condition under NMDAR blockage.
Given the robust evidence of antisaccade deficits in schizophrenia spectrum populations, the current findings suggest that ketamine may not mimic all features of psychosis at the dose used in this study. Our findings underline the importance of a more detailed research to further understand and define effects of NMDAR hypofunction on human brain function and behavior, with a view to applying ketamine administration as a model system of psychosis. Future studies with varying doses will be of importance in this context.
KeywordsInhibitory control Antisaccades Ketamine Schizophrenia Psychosis Eye movements Experimental model system
The authors thank Sam Hutton, Marcel Bartling, and Peter Trautner for their excellent technical support. The authors would like to thank Helen Röhrig and Inken Salhofen for their assistance in data collection and all volunteers who participated in the study.
The study was funded by the German Research Foundation (Deutsche Forschungsgemeinschaft; Et 31/2-1). The funding body had no role in the design of the study, data analysis, data interpretation, or publication.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
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