Alterations in interhemispheric gamma-band connectivity are related to the emergence of auditory verbal hallucinations in healthy subjects during NMDA-receptor blockade.
Stephanie Thiebes, Saskia Steinmann, Stjepan Curic, Nenad Polomac, Christina Andreou, Iris-Carola Eichler, Lars Eichler, Christian Zöllner, Jürgen Gallinat, Gregor Leicht, Christoph Mulert
Neuropsychopharmacology February 5, 2018 DOI: 10.1038/s41386-018-0014-z (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Single-blind, pseudo-randomized, placebo-controlled crossover study Peer reviewed |
|---|---|
| Sample size | 19 |
| Population | Healthy male, right-handed volunteers |
| Intervention | Ketamine |
| Measures | PANSS, 5D-ASC questionnaire including AUA-AVD/AVH subscale, eLORETA source estimation, lagged phase synchronization (LPS) in gamma-band (30-100 Hz) |
| Topics | Ketamine |
| Keywords | Humans Hallucinations Receptors, n-methyl-d-aspartate Electroencephalography Dichotic listening tests Cross-over studies Single-blind method Auditory perception Adolescent Male Young adult Healthy volunteers Gamma rhythm |
| Key points | Ketamine altered interhemispheric gamma-band connectivity between bilateral auditory cortices and induced hallucinations and auditory verbal distortions in a subgroup of healthy volunteers; those reporting auditory alterations had significantly higher interhemispheric gamma connectivity than those who did not. The authors argue this supports the interhemispheric miscommunication hypothesis of auditory verbal hallucinations and a possible role of glutamate in schizophrenia. |
Abstract
Auditory verbal hallucinations (AVH) are a common positive symptom of schizophrenia. Excitatory-to-inhibitory (E/I) imbalance related to disturbed N-methyl-D-aspartate receptor (NMDAR) functioning has been suggested as a possible mechanism underlying altered connectivity and AVH in schizophrenia. The current study examined the effects of ketamine, a NMDAR antagonist, on glutamate-related mechanisms underlying interhemispheric gamma-band connectivity, conscious auditory perception during dichotic listening (DL), and the emergence of auditory verbal distortions and hallucinations (AVD/AVH) in healthy volunteers. In a single-blind, pseudo-randomized, placebo-controlled crossover design, nineteen male, right-handed volunteers were measured using 64 channel electroencephalography (EEG). Psychopathology was assessed with the PANSS interview and the 5D-ASC questionnaire, including a subscale to detect auditory alterations with regard to AVD/AVH (AUA-AVD/AVH). Interhemispheric connectivity analysis was performed using eLORETA source estimation and lagged phase synchronization (LPS) in the gamma-band range (30-100 Hz). Ketamine induced positive symptoms such as hallucinations in a subgroup of healthy subjects. In addition, interhemispheric gamma-band connectivity was found to be altered under ketamine compared to placebo, and subjects with AUA-AVD/AVH under ketamine showed significantly higher interhemispheric gamma-band connectivity than subjects without AUA-AVD/AVH. These findings demonstrate a relationship between NMDAR functioning, interhemispheric connectivity in the gamma-band frequency range between bilateral auditory cortices and the emergence of AVD/AVH in healthy subjects. The result is in accordance with the interhemispheric miscommunication hypothesis of AVH and argues for a possible role of glutamate in AVH 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 12
- Glutamatergic Deficits in Schizophrenia – Biomarkers and Pharmacological Interventions within the Ketamine Model Current Pharmaceutical Biotechnology June 21, 2018
- The Altered States Database: Psychometric data from a systematic literature review. Scientific Data November 23, 2022
- High-order brain interactions in ketamine during rest and task: a double-blinded cross-over design using portable EEG on male participants. Translational Psychiatry July 27, 2024
- Opposite Modulation of the NMDA Receptor by Glycine and S-Ketamine and the Effects on Resting State EEG Gamma Activity: New Insights into the Glutamate Hypothesis of Schizophrenia International Journal of Molecular Sciences January 18, 2023
- Effects of N-Methyl-d-Aspartate Receptor Antagonists on Gamma-Band Activity During Auditory Stimulation Compared With Electro/Magneto-encephalographic Data in Schizophrenia and Early-Stage Psychosis: A Systematic Review and Perspective. Schizophrenia Bulletin August 27, 2024
and 7 more in the library
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and 1 more in the library