Functional connectivity alterations of the pregenual anterior cingulate cortex by ketamine and the modulation by lamotrigine.
David Weigner, Marvin Sören Meiering, Anne Weigand, Luisa Carstens, Christian Keicher, Rita Hertrampf, Christian Beckmann, Maarten Mennes, Andreas Wunder, Matti Gärtner, Simone Grimm
Journal of Psychopharmacology June 19, 2025 DOI: 10.1177/02698811251346705 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, placebo-controlled, randomized, single-dose, parallel-group study Peer reviewed |
|---|---|
| Sample size | 75 |
| Population | Healthy participants |
| Interventions | Ketamine Lamotrigine |
| Duration | Single dose, 24 h follow-up |
| Topics | Ketamine Esketamine |
| Keywords | Resting state Working memory Ketamine ketamine Mental health benefits Positive changes Effects Altered brain communication Enhance functional connectivity Brain areas Lamotrigine pretreatment |
| Key points | Ketamine infusion enhanced functional connectivity in key neural networks, and these effects were blocked by lamotrigine pretreatment, indicating a role for glutamate release. |
Abstract
Neuroimaging studies have linked the beneficial effects of subanaesthetic ketamine doses in psychiatric conditions characterized by chronic stress pathology (CSP) to altered functional connectivity (FC) within the pregenual anterior cingulate cortex (pgACC). Previous research indicates a potential role of glutamate concentration in FC changes; however, the precise relationship between glutamate release and increased FC remains unclear. Lamotrigine, a glutamate-release inhibitor, allows deeper exploration of this relationship. Additionally, CSP and treatment efficacy are closely associated with alterations in working memory (WM), necessitating the examination of FC during resting state and WM tasks. This study aimed to investigate the acute and sustained effects of altered glutamate transmission induced by ketamine and lamotrigine on pgACC FC during rest and WM. In this double-blind, placebo-controlled, randomized, single-dose, parallel-group study, resting-state and task-related functional Magnetic Resonance Imaging (fMRI) data were collected at baseline, during and 24 h after ketamine administration in 75 healthy participants. Participants were randomized to receive ketamine, ketamine with lamotrigine pretreatment or placebo. FC analyses utilized pgACC masks derived from the Julich Brain Atlas. Ketamine infusion significantly enhanced FC between the pgACC and dorsomedial prefrontal cortex during the WM task, and increased resting-state FC between the pgACC and left insula. These effects were absent following lamotrigine pretreatment. The findings support the hypothesis that ketamine's favourable effects, reflected by enhanced FC within key neural networks, may be attributable to glutamate release.
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
Cites 25
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- 20 years of the default mode network: A review and synthesis Neuron May 10, 2023
- The Standardized Psychometric Assessment of Altered States of Consciousness (ASCs) in Humans Pharmacopsychiatry July 1, 1998
- Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis Journal of Affective Disorders September 23, 2020
- Glutamate and the Neural Basis of the Subjective Effects of Ketamine Archives of General Psychiatry February 1, 2008
and 20 more in the library