Ketamine-dependent neuronal activation in healthy volunteers.
Anna S. Höflich, Andreas Hahn, Martin Küblböck, Georg S. Kranz, Thomas Vanicek, Sebastian Ganger, Marie Spies, Christian Windischberger, Siegfried Kasper, Dietmar Winkler, Rupert Lanzenberger
Brain Structure and Function April 2017 DOI: 10.1007/s00429-016-1291-0 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, randomized, placebo-controlled, crossover study Peer reviewed |
|---|---|
| Sample size | 35 |
| Population | Healthy volunteers |
| Intervention | Esketamine (Ketanest S®) |
| Duration | 55-minute resting-state fMRI scan |
| Measures | BOLD signal |
| Topics | Ketamine Esketamine |
| Keywords | Anterior cingulate gyrus Insula Thalamus FMRI |
| Key points | Compared with placebo, esketamine increased neural activation in the midcingulate cortex, dorsal anterior cingulate cortex, bilateral insula, and thalamus, and decreased activation in the subgenual/subcallosal anterior cingulate cortex, orbitofrontal cortex, and gyrus rectus. The authors propose these findings help clarify the neurobiological correlates of ketamine's antidepressant effects. |
Abstract
Over the last years, a number of studies have been conducted to clarify the neurobiological correlates of ketamine application. However, comprehensive information regarding the influence of ketamine on cortical activity is still lacking. Using resting-state functional MRI and integrating pharmacokinetic information, a double-blind, randomized, placebo-controlled, crossover study was performed to determine the effects of ketamine on neuronal activation. During a 55 min resting-state fMRI scan, esketamine (Ketanest S®) was administered intravenously to 35 healthy volunteers. Neural activation as indicated by the BOLD signal using the pharmacokinetic curve of ketamine plasma levels as a regressor was computed. Compared with placebo, ketamine-dependent increases of neural activation were observed in the midcingulate cortex, the dorsal part of the anterior cingulate cortex, the insula bilaterally, and the thalamus (t values ranging between 5.95-9.78, p < 0.05; FWE-corrected). A significant decrease of neural activation in the ketamine condition compared to placebo was found in a cluster within the subgenual/subcallosal part of the anterior cingulate cortex, the orbitofrontal cortex and the gyrus rectus (t = 7.81, p < 0.05, FWE-corrected). Using an approach combining pharmacological and fMRI data, important information about the neurobiological correlates of the clinical antidepressant effects of ketamine could be revealed.
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 22
- Subanaesthetic ketamine and altered states of consciousness in humans British Journal of Anaesthesia April 13, 2018
- The anterior cingulate cortex as a key locus of ketamine’s antidepressant action Neuroscience & Biobehavioral Reviews May 10, 2021
- The Psychedelic Future of Post-Traumatic Stress Disorder Treatment Current Neuropharmacology January 5, 2024
- The neurophysiology of ketamine: an integrative review Reviews in the Neurosciences May 5, 2020
- Glutamatergic Deficits in Schizophrenia – Biomarkers and Pharmacological Interventions within the Ketamine Model Current Pharmaceutical Biotechnology June 21, 2018
and 17 more in the library
Cites 18
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- Glutamate and the Neural Basis of the Subjective Effects of Ketamine Archives of General Psychiatry February 1, 2008
- Ketamine Decreases Resting State Functional Network Connectivity in Healthy Subjects: Implications for Antidepressant Drug Action PLoS One September 24, 2012
and 13 more in the library