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 (Oxford, England) June 19, 2025 DOI: 10.1177/02698811251346705 via PubMed
Summary
AI-generated from the abstractKetamine infusion significantly increased functional connectivity between the pregenual anterior cingulate cortex and the dorsomedial prefrontal cortex during a working memory task, and between the pregenual anterior cingulate cortex and the left insula during rest. These effects were absent when participants were pretreated with lamotrigine, a glutamate-release inhibitor. The findings suggest that ketamine's beneficial effects on brain communication, observed in psychiatric conditions linked to chronic stress, may depend on glutamate release.
Study at a glance
| 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 |
| Keywords | Resting state Working memory Ketamine ketamine Mental health benefits Positive changes |
| Key finding | 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.