Causal Role of Noradrenaline in the Timing of Internally Generated Saccades in Monkeys.

We recently found that when monkeys performed an oculomotor version of the time production task, the trial-by-trial latency of self-timed saccades was negatively correlated with pupil diameter just before the delay period (Suzuki et al., 2016). Since pupil diameter has been shown to correlate with neuronal activity in the locus coeruleus, the level of noradrenaline (NA) in the brain might regulate the subjective passage of time. To examine this, we orally administered a selective noradrenaline reuptake inhibitor (reboxetine, 0.4-0.8 mg) when animals made a self-initiated memory-guided saccade >1 s following the appearance of a brief visual cue. We found that reboxetine delayed self-timed saccades, while the latency of visually triggered saccades remained unchanged. Because the changes in proportions and latencies of early impulsive saccades were comparable between conditions with and without drug administration, alteration of self-timing might not result from reduced impulsivity. We also assessed other behavioral parameters (saccade accuracy, velocity, and latency variance), but failed to find any drug effect except for the accuracy of visually triggered saccades in the high-dose condition, indicating that reboxetine specifically altered self-timing under our experimental conditions. Our results suggest that NA-related internal states may causally regulate temporal information processing in the brain.