Neuropharmacological evidence for different timing mechanisms in humans

Temporal processing of intervals in the range of seconds or more is cogniti vely mediated, whereas processing of brief durations below 500 msec appears to be based on brain mechanisms outside cognitive control. To elucidate th e critical role of various neurotransmitters in timing processes in humans, the effects of 3 mg of haloperidol, a dopamine receptor antagonist, 11 mg of the benzodiazepine midazolam, and 1 mg of scopolamine, a cholinergic rec eptor antagonist, were compared in a placebo-controlled double-blind experi ment. In addition, changes in cortical arousal, semantic memory, and cognit ive and motor skill acquisition were assessed. Temporal processing of long durations was significantly impaired by haloperiodol and midazolam, whereas processing of extremely brief intervals was only affected by haloperidol. The overall pattern of results supports the notion that temporal processing of longer intervals is mediated by working-memory functions and, therefore , any pharmacological treatment, irrespective of the neurotransmitter syste m involved, that produces a deterioration of working memory, may interfere with temporal processing of longer intervals. Temporal processing of interv als in the range of milliseconds appears to depend on the effective level o f dopaminergic activity in the basal ganglia.