Reduced early auditory evoked gamma-band response in ketamine model of schizophrenia

Ketamine, an antagonist of the glutamatergic N-methyl-D-aspartate (NMDA) receptor, has been used to elicit behavioral effects and altered neurophysiological measures similar to those seen in schizophrenia. Gamma-oscillations have been linked to the glutamatergic neurotransmission, mediated by a feedback loop between fast-spiking, parvalbumin-expressing interneurons and glutamatergic pyramidal cells. Moreover gamma-oscillations are known to be altered in patients with schizophrenia. The purpose of this study is to get a deeper insight in the underlying pathomechanisms of schizophrenia by investigating the effects of ketamine on the early auditory evoked gamma-band response (EAGBR), that has been reported to be reduced in patients with schizophrenia. In the present study we investigated the early EAGBR, its sources as well as behavioral changes in 25 right handed male healthy volunteers, during pharmacological electroencephalography. We are using a single-blind, randomized, placebo-controlled crossover design. We observed a reduction at the power of the EAGBR and the amplitude of N100. Response time and error rates were increased in the ketamine group. PANSS and 5D-ASC scores were increased in the ketamine group. In this study we showed that pharmacologically reduced glutamatergic neurotransmission leads to an impaired EAGBR and schizophrenia-like cortical dysfunction, emphasizing the important role of glutamatergic neurotransmission in the development of schizophrenia. This study was supported by This study was part of the Collaborative Research Center 936, funded by the German Research Foundation