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Beneficial Effects of the NMDA Antagonist Ketamine on Decision Processes in Visual Search

The ability of sensory-motor circuits to integrate sensory evidence over time is thought to underlie the process of decision-making in perceptual discrimination. Recent work has suggested that the NMDA receptor contributes to mediating neural activity integration. To test this hypothesis, we trained three female rhesus monkeys (Macaca mulatta) to perform a visual search task, in which they had to make a saccadic eye movement to the location of a target stimulus presented among distracter stimuli of lower luminance. We manipulated NMDA-receptor function by administering an intramuscular injection of the noncompetitive NMDA antagonist ketamine and assessed visual search performance before and after manipulation. Ketamine was found to lengthen response latency in a dose-dependent fashion. Surprisingly, it was also observed that response accuracy was significantly improved when lower doses were administered. These findings suggest that NMDA receptors play a crucial role in the process of decision-making in perceptual discrimination. They also further support the idea that multiple neural representations compete with one another through mutual inhibition, which may explain the speed–accuracy trade-off rule that shapes discrimination behavior: lengthening integration time helps resolve small differences between choice alternatives, thereby improving accuracy.