Region- and time- specific effects of ketamine on cerebral blood flow: a randomized controlled trial.
Matti Gärtner, Anne Weigand, Marvin Sören Meiering, David Weigner, Luisa Carstens, Christian Keicher, Rita Hertrampf, Christian Beckmann, Maarten Mennes, Andreas Wunder, Simone Grimm
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology May 25, 2023 DOI: 10.1038/s41386-023-01605-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, placebo-controlled, randomized, parallel-group study Peer reviewed |
|---|---|
| Sample size | 75 |
| Population | Healthy participants |
| Interventions | Ketamine Lamotrigine |
| Duration | Two scanning sessions (acute/post 24 h.) |
| Measures | arterial spin labeling, blood oxygen level dependent (BOLD) imaging |
| Topics | Ketamine Esketamine |
| Keywords | Brain Humans Glutamates Anticonvulsants Cerebrovascular circulation Lamotrigine |
| Key points | Acute ketamine increased perfusion in the inferior frontal gyrus and dorsolateral prefrontal cortex, but no other investigated region; lamotrigine pretreatment abolished this effect. At 24 hours, lamotrigine pretreatment was associated with lower inferior frontal gyrus perfusion. The authors argue these regionally selective cerebral blood flow changes reflect proximate effects of glutamate release on neuronal activity, with sustained effects indicating rapid restoration of disturbed homeostasis in the dorsolateral prefrontal cortex and changes beyond immediate glutamate signaling in the inferior frontal gyrus. |
Abstract
There is intriguing evidence suggesting that ketamine might have distinct acute and delayed neurofunctional effects, as its acute administration transiently induces schizophrenia-like symptoms, while antidepressant effects slowly emerge and are most pronounced 24 h after administration. Studies attempting to characterize ketamine's mechanism of action by using blood oxygen level dependent (BOLD) imaging have yielded inconsistent results regarding implicated brain regions and direction of effects. This may be due to intrinsic properties of the BOLD contrast, while cerebral blood flow (CBF), as measured with arterial spin labeling, is a single physiological marker more directly related to neural activity. As effects of acute ketamine challenge are sensitive to modulation by pretreatment with lamotrigine, which inhibits glutamate release, a combination of these approaches should be particularly suited to offer novel insights. In total, 75 healthy participants were investigated in a double blind, placebo-controlled, randomized, parallel-group study and underwent two scanning sessions (acute/post 24 h.). Acute ketamine administration was associated with higher perfusion in interior frontal gyrus (IFG) and dorsolateral prefrontal cortex (DLPFC), but no other investigated brain region. Inhibition of glutamate release by pretreatment with lamotrigine abolished ketamine's effect on perfusion. At the delayed time point, pretreatment with lamotrigine was associated with lower perfusion in IFG. These findings underscore the idea that regionally selective patterns of CBF changes reflect proximate effects of modulated glutamate release on neuronal activity. Furthermore, region- specific sustained effects indicate both a swift restoration of disturbed homeostasis in DLPFC as well changes occurring beyond the immediate effects on glutamate signaling in IFG.
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 |