Effects of pharmacologically induced changes in NMDA receptor activity on human timing and sensorimotor performance

Unlike processing of time intervals in the range of seconds or more, processing of brief durations in the subsecond range appears to be beyond cognitive control and based on subcortical mechanisms located in the basal ganglia. The present study was designed to evaluate the effects of NMDA receptor activity on temporal processing in the second and subsecond range. In a double-blind crossover design, either 30 mg of the noncompetitive NMDA receptor antagonist memantine or placebo was administered to 32 healthy male volunteers. While memantine induced a marked impairment in temporal processing of intervals in the range of seconds, temporal processing of intervals in the range of milliseconds was not affected. Furthermore, no effect of memantine on speed of information processing could be observed. Speed of motor response execution, however, was significantly enhanced by memantine compared to placebo. The overall pattern of results provides converging evidence for the notion that temporal processing of longer intervals involves higher order working memory functions such as working memory capacity. The absence of an effect on temporal processing of very brief intervals in combination with the beneficial effect on movement time suggests that NMDA receptor activity in the basal ganglia is not directly related to the timing of intervals in the subsecond range.