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.
Comparable studies
Other randomized controlled trials on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Healthy human subjects recruited from the community | 1994 | Randomized controlled trial | n = 19 |
| Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode | 2013 | Randomized controlled trial | n = 73 |
| Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine Patients undergoing major abdominal surgery | 2005 | Randomized controlled trial | n = 75 |
| Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder Patients with chronic PTSD related to a range of trauma exposures | 2014 | Randomized controlled trial | n = 41 |
| Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers Healthy volunteers | 2000 | Single-blind placebo-controlled study | n = 20 |
Citations in the library
Cited by 2
Cites 11
- Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Journal of Neuroscience April 15, 1997
- Disruption of Frontal–Parietal Communication by Ketamine, Propofol, and Sevoflurane Anesthesiology May 22, 2013
- The spectral exponent of the resting EEG indexes the presence of consciousness during unresponsiveness induced by propofol, xenon, and ketamine Neuroimage January 11, 2019
- Comparative and Interactive Human Psychopharmacologic Effects of Ketamine and Amphetamine Archives of General Psychiatry September 1, 2005
- Association of Ketamine With Psychiatric Symptoms and Implications for Its Therapeutic Use and for Understanding Schizophrenia JAMA Network Open May 1, 2020
and 6 more in the library