Ketamine reduces temporal expectation in the rhesus monkey.

RATIONALE: Ketamine, a well-known general dissociative anesthetic agent that is a non-competitive antagonist of the N-methyl-D-aspartate receptor, perturbs the perception of elapsed time and the expectation of upcoming events. OBJECTIVE: The objective of this study was to determine the influence of ketamine on temporal expectation in the rhesus monkey. METHODS: Two rhesus monkeys were trained to make a saccade between a central warning stimulus and an eccentric visual target that served as imperative stimulus. The delay between the warning and the imperative stimulus could take one of four different values randomly with the same probability (variable foreperiod paradigm). During experimental sessions, a subanesthetic low dose of ketamine (0.25-0.35 mg/kg) was injected i.m. and the influence of the drug on movement latency was measured. RESULTS: We found that in the control conditions, saccadic latencies strongly decreased with elapsed time before the appearance of the visual target showing that temporal expectation built up during the delay period between the warning and the imperative stimulus. However, after ketamine injection, temporal expectation was significantly reduced in both subjects. In addition, ketamine also increased average movement latency but this effect could be dissociated from the reduction of temporal expectation. CONCLUSION: In conclusion, a subanesthetic dose of ketamine could have two independent effects: increasing reaction time and decreasing temporal expectation. This alteration of temporal expectation could explain cognitive deficits observed during ketamine use.