Emotionalcognitive processing and brain metabolism after pharmacological challenge with ketamine
Simone Grimm, Milan Scheidegger, A Henning, Martin Walter, Anne Weigand, Heinz Böker, Malek Bajbouj, Erich Seifritz
Pharmacopsychiatry September 1, 2011 DOI: 10.1055/s-0031-1292482 via OpenAlex
Summary
Ketamine, a glutamatergic NMDA receptor antagonist with rapid antidepressant properties, was used to investigate the neurobiology of major depressive disorder. In a multimodal imaging study of 23 healthy subjects, a single ketamine infusion increased negative BOLD responses in brain regions involved in emotional processing, particularly limbic areas linked to emotional information and higher-order mental functions. During cognitive processing, ketamine affected negative BOLD responses in anterior but not posterior regions of the default-mode network. Strong correlations were found between glutamate, glutamine, GABA, and glutamine/glutamate ratios and these brain responses after ketamine administration, suggesting a link to glutamatergic neurotransmission.
Study at a glance
| Characteristics | Multimodal imaging study Peer reviewed |
|---|---|
| Sample size | 23 |
| Population | Healthy subjects |
| Intervention | Ketamine infusion |
| Topics | Depression Ketamine |
| Keywords | Glutamatergic Glutamate receptor Neuroscience Nmda receptor |
| Key finding | Ketamine administration increased negative BOLD responses in limbic brain areas during emotional processing and in anterior default-mode network regions during cognitive processing, with strong correlations to glutamatergic metabolites. |
Abstract
Ketamine is a potent glutamatergic NMDA receptor antagonist with rapid antidepressant properties, thus providing a valuable research tool for the investigation of the neurobiology of major depressive disorder (MDD). Increasing evidence underscores the role of glutamate dependent neuroplasticity and glutamatergic neurotransmission and metabolism in the pathophysiology of MDD. This multimodal imaging study in 23 healthy subjects aimed at probing the neuropharmacological effects of a single ketamine infusion on fMRI-BOLD responses during emotional/cognitive processing and their relationship to glutamatergic metabolite concentrations assessed by proton magnetic resonance spectroscopy (1H-MRS). During emotional processing there was a brain region-specific increase in negative BOLD responses (NBRs) following ketamine administration. The most significant BOLD differences were found in predominantly limbic brain areas associated with the processing of emotional information and higher-order mental functions. During cognitive processing there was a significant ketamine effect on NBRs in anterior, but not posterior regions of the default- mode network. A strong correlation between glutamate, glutamine, GABA as well as glutamine/glutamate ratios (a putative marker for glutamatergic neurotransmission) and NBRs could be found after ketamine administration.