Setting the beat of an internal clock: Effects of dexamphetamine on different interval ranges of temporal processing in healthy volunteers

Abstract

Drug studies are powerful models to investigate the neuropharmacological mechanisms underlying temporal processing in humans. This study administered dexamphetamine to 24 healthy volunteers to investigate time perception at different time scales, along with contributions from working memory. Healthy volunteers were administered 0.45 mg/kg dexamphetamine or placebo in a double-blind, crossover, placebo-controlled design. Time perception was assessed using three experimental tasks: a time-discrimination task, which asked participants to determine whether a comparison interval (1200 ± 0, 50, 100, 150, 200 ms) was shorter or longer than a standard interval (1200 ms); a retrospective time estimation task, which required participants to verbally estimate time intervals (10, 30, 60, 90 and 120 s) retrospectively; and a prospective time-production task, where participants were required to prospectively monitor the passing of time (10, 30, 60, 90 and 120 s). Working memory was assessed with the backwards digit span. On the discrimination task, there was a change in the proportion of long-to-short responses and reaction times in the dexamphetamine condition (but no association with working memory), consistent with an increase in the speed of an internal pacemaker, and an overestimation of durations in the timing of shorter intervals. There was an interaction between dexamphetamine, working memory, and performance on the estimation and production tasks, whereby increasing digit span scores were associated with decreasing interval estimates and increased produced intervals in the placebo condition, but were associated with increased interval estimates and decreased produced intervals after dexamphetamine administration. These findings indicate that the dexamphetamine-induced increase in the speed of the internal pacemaker was modulated by the basal working memory capacity of each participant. These findings in healthy humans have important implications for the role of dopamine, and its contributions to timing deficits, in models of psychiatric disorders.