Gamma Oscillations and Excitation/Inhibition Imbalance: Parallel Effects of NMDA Receptor Antagonism and Psychosis.
Brian J Roach, Judith M. Ford, Spero Nicholas, Jamie M Ferri, Handan Gunduz-Bruce, John H. Krystal, Judith Jaeger, Daniel H. Mathalon
Biological psychiatry. Cognitive neuroscience and neuroimaging January 18, 2025 DOI: 10.1016/j.bpsc.2025.01.008 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Crossover, placebo-controlled drug challenge study and case-control study Peer reviewed |
|---|---|
| Population | Healthy participants and patients with schizophrenia |
| Intervention | Ketamine |
| Topics | Ketamine |
| Keywords | Electroencephalography EEG Nmda receptor nmdar Schizophrenia Mental illness research Gamma waves Assr EEG Patterns |
| Citations | 7 |
| Key findings | Ketamine-induced 40-Hz ASSR abnormalities resembled those in schizophrenia except for phase, supporting NMDA receptor hypofunction's role in gamma oscillation deficits in schizophrenia. |
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.