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

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.