Gamma oscillations and excitation/inhibition imbalance: parallel effects of N-methyl D-aspartate receptor antagonism and psychosis.

Abstract

Background: Auditory steady-state response (ASSR) abnormalities in the 40-Hz (gamma band) frequency have been observed in schizophrenia and rodent studies of N-methyl D-aspartate glutamate receptor (NMDAR) hypofunction. However, the extent to which 40-Hz ASSR abnormalities in schizophrenia resemble deficits in 40-Hz ASSR induced by acute administration of ketamine, an NMDAR antagonist, is not yet known.

Methods: To address this knowledge gap, we conducted parallel EEG studies: a crossover, placebo-controlled ketamine drug challenge study in healthy subjects (Study 1) and a comparison of patients with schizophrenia and healthy controls subjects (Study 2). Time-frequency analysis of the ASSR was used to calculate baseline, broadband gamma power, evoked power, total power, phase-locking factor, and phase-locking angle.

Results: Relative to healthy controls, schizophrenia patients exhibited increases in pre-stimulus broadband gamma power and reductions in 40-Hz ASSR evoked power, total power, and phase-locking factor, replicating prior studies. However, we failed to replicate previous findings of 40-Hz ASSR phase delay in schizophrenia. Relative to placebo, ketamine: increased pre-stimulus broadband gamma power, reduced 40-Hz ASSR evoked power, total power, and phase-locking factor, and advanced the phase of the 40-Hz ASSR.

Conclusion: Normalized by their respective control groups/conditions, direct comparison of these measures between schizophrenia and ketamine data only revealed significant differences in phase, supporting the role of NMDAR hypofunction in mediating gamma oscillation abnormalities in schizophrenia.