The effects of glutamatergic modulation on human auditory perception and behavioural changes in a Mismatch Negativity (MMN) paradigm

Abstract

Subanasthetic doses of ketamine, a N-methyl-D-aspartate (NMDA)-receptor antagonist, have been used to model behavioural and neurophysiological effects reminiscent of schizophrenia in order to investigate the role of the glutamatergic system in the development of the disease. Significant alterations in event related potentials (ERPs) have been documented in schizophrenic patients and in healthy controls receiving ketamine. The Mismatch Negativity (MMN), a response to tone duration or frequency deviant, has been shown to be reduced. In the current study we examine the impact of ketamine on auditory perception with 64-channel EEG and a MMN paradigm. Twenty-five male, healthy volunteers were measured with pharmacological electroencephalography (EEG) using a single-blind, randomized, placebo-controlled crossover design. After placebo and ketamine intervention, psychopathological status was assessed using the Altered State of Consciousness (5D-ASC) Rating Scale and the Positive and Negative Syndrome Scale (PANSS). We found that MMN is diminished in the ketamine condition accompanied by significant changes of behavioural and cognitive scales in the 5D-ASC and the PANSS. Scores of the questionnaires describing alterations in auditory perception have increased indicating an impact of the NMDA-receptor in this domain. Our results suggest that a glutamatergic modulation mimics specific impairments as described for schizophrenia both in the EEG and at the behavioural level.