Examining the Pharmacology of Mismatch Negativity: An Electrophysiological Investigation in Healthy Subjects

Schizophrenia is associated with impairments in pre-attentive change detection, as represented by reduced mismatch negativity (MMN) amplitudes. While most researchers believe that this reduced MMN is primarily due to the impaired glutamate (GLU) system, mediated by N-methyl-D-aspartate (NMDA) receptors, it is yet to clarify whether imbalances in other neurotransmitter systems contribute to this diminished MMN. Among the various neurotransmitter systems, whether dopamine (DA) imbalance in schizophrenia contributes to the attenuated MMN is of particular interest, because the two main neurochemical hypotheses of this disorder are the GLU and the DA hypotheses. In addition, given that the serotonin (5HT) system is also involved in the disorder, and glycine (an NMDA receptor co-agonist) has been trialled as an adjunct therapy in schizophrenia, the role of the 5HT system and the effect of glycine in MMN generation also warrant investigation. However, it is difficult to examine these issues from the clinical MMN studies due to