Gamma Oscillations and Excitation/Inhibition Imbalance: Parallel Effects of NMDA Receptor Antagonism and Psychosis.
Biological psychiatry. Cognitive neuroscience and neuroimaging – January 18, 2025
Source: PubMed
Summary
Brain wave patterns in schizophrenia mirror those caused by ketamine, revealing a crucial link. Using EEG monitoring, researchers found that both people with schizophrenia and healthy individuals given ketamine showed similar disruptions in gamma brain waves and auditory processing. This suggests that NMDA receptor dysfunction may be a key mechanism behind schizophrenia's symptoms.
Abstract
Auditory steady-state response (ASSR) abnormalities in the 40-Hz (gamma band) frequency have been observed in schizophrenia and in rodent studies of NMDA 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. To address this knowledge gap, we conducted parallel electroencephalography studies: a crossover, placebo-controlled ketamine drug challenge study with healthy participants (study 1) and a comparison of patients with schizophrenia and healthy control participants (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. Relative to healthy control participants, patients with schizophrenia exhibited increases in prestimulus broadband gamma power and reductions in 40-Hz ASSR evoked power, total power, and phase-locking factor, replicating previous studies. However, we failed to replicate previous findings of 40-Hz ASSR phase delay in schizophrenia. Relative to placebo, ketamine increased prestimulus broadband gamma power; reduced 40-Hz ASSR evoked power, total power, and phase-locking factor; and advanced the phase of the 40-Hz ASSR. 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.