These abnormalities in GABAergic transmission appear to be associated with NMDAR dysfunction and dysfunctional NMDAR, in turn, causes abnormal neuronal plasticity, which is thought to be a crucial pathophysiological process in schizophrenia patients [38]. A theory about abnormal synaptic plasticity from Stephan, Friston and Frith discussed the relationship between dysfunctional NMDAR and disconnectivity in schizophrenia patients [38]. In their theory, the underlying biological and pathophysiological agent of schizophrenia is a dysfunction of NMDAR with a consecutive reduced synaptic and cellular plasticity. This would affect long-range connections in the developing brain, induce abnormalities in different neurotransmitter systems (dopamine, serotonine, acetylcholine, GABA), lead to aberrant corollary discharge and to impaired perceptual interference. This theory and other theories, discussing the glutamate-hypothesis of schizophrenia, are supported by several lines of evidence. A reduced LTP-like focal, spike-timing-dependent-like synaptic plasticity and a reduced LTP-like non-focal, cortical plasticity are recent neurophysiological findings in schizophrenia patients [14, 20]. Taken together, this may indicate dysfunctional NMDARs and a reduced signal-to-noise ratio with consecutive dysfunctional information processing [20]. Additionally, numerous studies display a link between NMDAR dysfunction and affected cortical oscillations and mismatched negativity deficits [40].
