Ketamine perturbs perception of the flow of time in healthy volunteers

Abstract

Rationale: Disturbances in the subjective experience of time have been observed both in schizophrenia and following acute administration of ketamine. However, effects of ketamine on more objective timing tasks have not yet been measured in humans, nor has it been established that timing effects are not merely secondary to a more general dysfunction in working memory (WM).

Objective and methods: In a double-blind placebo-controlled crossover study, we characterised the effects of ketamine (100 ng/ml blood plasma level) on performance of perceptual timing and colour discrimination tasks, which were matched for WM and attentional demands. To test the ubiquity of ketamine's effects on timing, we also examined two distinct measures of temporal predictability.

Results: Ketamine significantly distorted the subjective experience of time as measured by the Clinician-Administered Dissociative States Scales. Critically, ketamine also impaired accuracy on the perceptual timing task while having no effect on performance of the colour perception task. Although ketamine did not impair the ability to use prelearned temporal (or spatial) cues to predict target onset (or location), it did slow reaction times at long delays following non-informative neutral cues, suggesting an impaired ability to use the unidirectional flow of time itself to make temporal predictions.

Conclusions: Ketamine induced selective impairments in timing, which could not be explained by more fundamental effects on the ability to hold information in WM. Rather our collected findings suggest that ketamine may disturb timing by selectively impairing the way in which information is temporally manipulated within WM.

Fig. 1

Temporal and colour discrimination task. Participants estimated either the duration or colour of two consecutive stimuli. The first (sample) and second (probe) stimuli were presented for one of three durations (540, 1,080, 1,620 ms) and had an overall percept of one of three shades of purple (maroon, violet or indigo). Stimuli were not of a uniform colour but instead comprised rapidly flickering (90 ms) presentations of three of five different shades of purple (see inset) to give the overall colour percept. Participants indicated whether the probe was shorter (S), longer (L) or the same (=) duration as the sample (‘time’ condition) or redder (R), bluer (B) or the same (=) shade of purple as the sample (‘colour’ condition) using a three-choice button press at the onset of the response screen

Fig. 2

Temporal and spatial-orienting task. Participants detected a target appearing at one of two peripheral locations (left/right) after one of two cue-target intervals (short/long) as quickly as possible. In the spatial or temporal condition, the visual cue predicted where or when (respectively) the target was likely to appear, with 80% validity. In the neutral condition, the visual cue carried neither spatial nor temporal information

Fig. 3

Ketamine impairs perceptual timing. a Ketamine selectively impaired accuracy (% correct) of time discrimination, while having no effect on accuracy of colour discrimination. b During the temporal discrimination task, ketamine significantly increased the likelihood (% trials) that the probe stimulus would be overestimated when the probe was shorter than (<) the sample. Error bars represent the standard error of the mean

Fig. 4

Ketamine attenuates the beneficial effect of the hazard function. The neutral cue condition of the orienting task produces faster RTs for targets appearing after long rather than short intervals due to the “hazard function”. Ketamine slowed RTs selectively at the long, not short, intervals, thus significantly attenuating the benefit that is normally afforded by long delays. Error bars represent the standard error of the mean