Ketamine disrupts consciousness in healthy participants in relation with psychotic-like symptoms.

Low doses of ketamine, an NMDA-receptor antagonist, disrupt the ability to consciously perceive visual information in healthy people. In a double-blind, placebo-controlled experiment with 21 volunteers, ketamine increased visual masking and reduced conscious perception of a digit. The N1 component of brain activity, an early marker of visual processing, was significantly reduced under ketamine and correlated with conscious access. Ketamine also induced psychotic-like and manic-like symptoms, but only the psychotic-like dimension was linked to impairments in conscious access. These findings suggest ketamine attenuates early visual brain responses, impairing conscious access, and that this mechanism differs in some ways from that seen in schizophrenia.

Study at a glance

Abstract

Ketamine is an NMDA-receptor antagonist, which alters the state of wakeful consciousness at high doses. At lower doses, it induces reversible psychotic-like symptoms and has been used as a pharmacological model of psychosis. In this study, we explore whether low doses of ketamine disrupt conscious access in relation with its psychotomimetic effects, and investigate the neural correlates of its action. We administered ketamine and placebo to 21 healthy volunteers following a double-blind within-subject randomized design and recorded brain activity with high-density electroencephalography during a perceptual task. Participants had to categorize a sound and a masked digit, and to report the digit visibility. To manipulate visibility, the delays between the sound, the digit, and the mask were varied. Principal component analysis was used to decompose ketamine-induced psychiatric symptoms and to examine their relationships with conscious access measures. Under ketamine, participants had an increased visual masking effect, more interference between the sound and the digit, and a reduced ability to consciously perceive the digit. The N1 component, a EEG marker of visual processing, correlated with conscious access and was significantly reduced under ketamine. Ketamine induced manic-like and psychotic-like symptoms but only the psychotic-like dimension correlated with conscious access impairments. Overall, our results suggest that ketamine disrupts conscious access in healthy subjects through an attenuation of early visual responses, and in relation with its psychotomimetic effects. Interestingly, these changes differed in part from those observed in patients with schizophrenia, opening new perspectives on the mechanisms of psychotic symptoms.