Ketamine-Induced Modulation of the Thalamo-Cortical Network in Healthy Volunteers As a Model for Schizophrenia
Anna S. Höflich, Andreas Hahn, Martin Küblböck, Georg S. Kranz, Thomas Vanicek, Christian Windischberger, Alois Saria, Siegfried Kasper, Dietmar Winkler, Rupert Lanzenberger
The International Journal of Neuropsychopharmacology April 19, 2015 DOI: 10.1093/ijnp/pyv040 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, randomized, placebo-controlled, crossover pharmacological functional MRI study Peer reviewed |
|---|---|
| Sample size | 30 |
| Population | Healthy volunteers |
| Intervention | Ketamine |
| Duration | 55-minute resting-state scan |
| Topics | Esketamine Ketamine |
| Citations | 130 |
| Key points | Ketamine challenge increased cortico-thalamic functional connectivity within the thalamus hub network, specifically involving the somatosensory and temporal cortex. The authors argue that this indicates NMDA-receptor blockade can partly mimic the thalamic changes described in schizophrenia, adding knowledge about mechanisms underlying altered perception and behavior with NMDA-receptor antagonists. |
Abstract
Background: Schizophrenia has been associated with disturbances of thalamic functioning. In light of recent evidence suggesting a significant impact of the glutamatergic system on key symptoms of schizophrenia, we assessed whether modulation of the glutamatergic system via blockage of the N-methyl-D-aspartate (NMDA)-receptor might lead to changes of thalamic functional connectivity.
Methods: Based on the ketamine model of psychosis, we investigated changes in cortico-thalamic functional connectivity by intravenous ketamine challenge during a 55-minute resting-state scan. Thirty healthy volunteers were measured with pharmacological functional magnetic resonance imaging using a double-blind, randomized, placebo-controlled, crossover design.
Results: Functional connectivity analysis revealed significant ketamine-specific changes within the thalamus hub network, more precisely, an increase of cortico-thalamic connectivity of the somatosensory and temporal cortex.
Conclusions: Our results indicate that changes of thalamic functioning as described for schizophrenia can be partly mimicked by NMDA-receptor blockage. This adds substantial knowledge about the neurobiological mechanisms underlying the profound changes of perception and behavior during the application of NMDA-receptor antagonists.
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 45
- Ketamine Has Distinct Electrophysiological and Behavioral Effects in Depressed and Healthy Subjects Molecular Psychiatry February 27, 2018
- Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms Pharmacological Reviews December 16, 2020
- Resting-state Network-specific Breakdown of Functional Connectivity during Ketamine Alteration of Consciousness in Volunteers Anesthesiology August 9, 2016
- Association of Ketamine With Psychiatric Symptoms and Implications for Its Therapeutic Use and for Understanding Schizophrenia JAMA Network Open May 1, 2020
- Substance-Induced Psychoses: An Updated Literature Review Frontiers in Psychiatry December 23, 2021
and 40 more in the library
Cites 12
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Default Mode Network Activity and Connectivity in Psychopathology Annual Review of Clinical Psychology March 29, 2012
- The Standardized Psychometric Assessment of Altered States of Consciousness (ASCs) in Humans Pharmacopsychiatry July 1, 1998
- Ketamine Decreases Resting State Functional Network Connectivity in Healthy Subjects: Implications for Antidepressant Drug Action PLoS One September 24, 2012
- NMDA receptor function in large-scale anticorrelated neural systems with implications for cognition and schizophrenia Proceedings of the National Academy of Sciences September 25, 2012
and 7 more in the library