Ketamine administration in healthy volunteers reproduces aberrant agency experiences associated with schizophrenia

Abstract

Introduction. Aberrant experience of agency is characteristic of schizophrenia. An understanding of the neurobiological basis of such experience is therefore of considerable importance for developing successful models of the disease. We aimed to characterise the effects of ketamine, a drug model for psychosis, on sense of agency (SoA). SoA is associated with a subjective compression of the temporal interval between an action and its effects: This is known as “intentional binding”. This action–effect binding provides an indirect measure of SoA. Previous research has found that the magnitude of binding is exaggerated in patients with schizophrenia. We therefore investigated whether ketamine administration to otherwise healthy adults induced a similar pattern of binding.Methods. 14 right-handed healthy participants (8 female; mean age 22.4 years) were given low-dose ketamine (100 ng/mL plasma) and completed the binding task. They also underwent structured clinical interviews.Results. Ketamine mimicked the performance of schizophrenia patients on the intentional binding task, significantly increasing binding relative to placebo. The size of this effect also correlated with aberrant bodily experiences engendered by the drug.Conclusions. These data suggest that ketamine may be able to mimic certain aberrant agency experiences that characterise schizophrenia. The link to individual changes in bodily experience suggests that the fundamental change produced by the drug has wider consequences in terms of individuals’ experiences of their bodies and movements.

Intentional binding and the sense of agency: A review

“…Although unexpected, this finding has been replicated in subsequent patient studies (Voss et al, 2010). This hyper-binding effect has also been induced in healthy controls following infusion of the drug ketamine (Moore, Turner, Corlett, et al, 2011). Ketamine is an anaesthetic agent which acts as an NDMA-receptor antagonist.…”

“…Moore, Turner, Corlett, et al (2011) showed that intentional binding was significantly stronger in participants on ketamine compared with their own performance on a placebo. This replicates the hyper-binding found in patients with schizophrenia.…”

Prediction error, ketamine and psychosis: An updated model

“…Taken together, these data confirm that PE-driven inferences are central to a range of experiences. Ketamine and psychosis similarly perturb these PEs, and those perturbations relate to the severity of endogenous and ketamine induced psychotic symptoms (Moore et al, 2011b). …”

Neurobiology of Schizophrenia: Search for the Elusive Correlation with Symptoms

“…This strategy is exemplified by the use of the NMDA-receptor antagonist, ketamine, in challenge studies with patients (Lahti et al, 1995) and healthy volunteers (Krystal et al, 1994, 2003; Adler et al, 1999; Umbricht et al, 2000; Moore et al, 2011; Neill et al, 2011), to test the hypothesis that NMDA-receptor hypofunction contributes to both clinical symptoms and neurocognitive deficits in schizophrenia.…”