Time, action and psychosis: using subjective time to investigate the effects of ketamine on sense of agency

Abstract

Sense of agency refers to the experience of initiating and controlling actions in order to influence events in the outside world. A disturbed sense of agency is found in certain psychiatric and neurological disorders, most notably schizophrenia. Sense of agency is associated with a subjective compression of time: actions and their outcomes are perceived as bound together in time. This is known as 'intentional binding' and, in healthy adults, depends partly on advance prediction of action outcomes. Notably, this predictive contribution is disrupted in patients with schizophrenia. In the present study we aimed to characterise the psychotomimetic effect of ketamine, a drug model for psychosis, on the predictive contribution to intentional binding. It was shown that ketamine produced a disruption that closely resembled previous data from patients in the early, prodromal, stage of schizophrenic illness. These results are discussed in terms of established models of delusion formation in schizophrenia. The link between time and agency, more generally, is also considered.

Fig. 1

(A) The intentional binding effect. Voluntary actions and outcomes are temporally bound together in experience, whereas involuntary movements and outcomes are separated in experience (see Haggard et al., 2002). (B) Operational definition of prediction in our study. A predictive contribution to action binding was derived from subtracting the shifts in the temporal experience of action on ‘action only’ trials in 50% effect probability condition, from shifts on action ‘only trials’ in the 75% effect probability condition.

Fig. 2

Data from previous studies on patients with schizophrenia and patients in the psychotic prodrome. These data represent the predictive contribution to action binding (i.e., the difference in binding on ‘action only’ trials in the 75% vs. 50% condition. The greater this difference the stronger the predictive contribution). Both studies replicated the predictive contribution to binding in healthy volunteers found by Moore and Haggard (2008). However, the two groups of patients showed different deficits on this task. Patients with schizophrenia showed no significant predictive contribution (from Voss et al. (2010)), whereas prodromal patients showed an excessive predictive contribution (from Hauser et al. (2011)).

Fig. 3

Trial structure in the agency condition (following Moore and Haggard (2008), Voss et al. (2010); Hauser et al., 2011). Participants pressed the key at a time of their choosing. In one condition the key pressed cause the tone on 50% of trials. In another condition, the key press caused the tone on 75% of trials. If the tone was played it was done after a delay of 250 ms from key press. Participants judged where the clock hand was when they pressed the key.

Fig. 4

Prediction-dependent shifts in action binding (ms) on placebo and ketamine. These shifts are calculated by subtracting binding on ‘action only’ trials in the 50% condition from binding on the same trials in the 75% condition. The more positive this difference the stronger the predictive effect. Error bars represent standard error of the mean.