Acute effects of ketamine on the pregenual anterior cingulate: linking spontaneous activation, functional connectivity, and glutamate metabolism
Matti Gärtner, Anne Weigand, Milan Scheidegger, Mick Lehmann, Patrik O. Wyss, Andreas Wunder, Anke Henning, Simone Grimm
European Archives of Psychiatry and Clinical Neuroscience January 12, 2022 DOI: 10.1007/s00406-021-01377-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 23 |
| Population | Healthy volunteers |
| Intervention | Ketamine |
| Topics | Ketamine Esketamine |
| Keywords | Anterior cingulate cortex Glutamine Glutamate receptor Glutamatergic Nmda receptor Cognition Biochemistry Gene |
| Citations | 13 |
| Key findings | Ketamine-induced stronger pgACC activation was linked to lower glutamine concentration in that region, and reduced functional connectivity between pgACC and aMCC was related to increased pgACC activation and reduced glutamine. |
Abstract
Abstract Ketamine exerts its rapid antidepressant effects via modulation of the glutamatergic system. While numerous imaging studies have investigated the effects of ketamine on a functional macroscopic brain level, it remains unclear how altered glutamate metabolism and changes in brain function are linked. To shed light on this topic we here conducted a multimodal imaging study in healthy volunteers ( N = 23) using resting state fMRI and proton ( 1 H) magnetic resonance spectroscopy (MRS) to investigate linkage between metabolic and functional brain changes induced by ketamine. Subjects were investigated before and during an intravenous ketamine infusion. The MRS voxel was placed in the pregenual anterior cingulate cortex (pgACC), as this region has been repeatedly shown to be involved in ketamine’s effects. Our results showed functional connectivity changes from the pgACC to the right frontal pole and anterior mid cingulate cortex (aMCC). Absolute glutamate and glutamine concentrations in the pgACC did not differ significantly from baseline. However, we found that stronger pgACC activation during ketamine was linked to lower glutamine concentration in this region. Furthermore, reduced functional connectivity between pgACC and aMCC was related to increased pgACC activation and reduced glutamine. Our results thereby demonstrate how multimodal investigations in a single brain region could help to advance our understanding of the association between metabolic and functional changes.
Comparable studies
Other observational and cohort studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Taming the Ketamine Tiger Volunteers from a prison population | 2010 | Observational study | n = 20 |
| Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin Humans | 2017 | Observational study | |
| Disruption of Frontal–Parietal Communication by Ketamine, Propofol, and Sevoflurane Surgical patients undergoing induction of anesthesia with intravenous ketamine | 2013 | Observational cohort | n = 30 |
| Do the dissociative side effects of ketamine mediate its antidepressant effects? Treatment-resistant inpatients with major depressive disorder or bipolar disorder | 2014 | Observational cohort | n = 108 |
| Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder Patients with treatment-resistant major depressive disorder | 2012 | Observational cohort | n = 30 |
Citations in the library
Cited by 8
- Association of the delayed changes in glutamate levels and functional connectivity with the immediate network effects of S-ketamine Translational Psychiatry February 16, 2023
- Ketamine and Zinc: Treatment of Anorexia Nervosa Via Dual NMDA Receptor Modulation CNS Drugs January 22, 2023
- Brain Networks, Neurotransmitters and Psychedelics: Towards a Neurochemistry of Self-Awareness. Current Neurology and Neuroscience Reports August 1, 2024
- Functional connectivity alterations of the pregenual anterior cingulate cortex by ketamine and the modulation by lamotrigine. Journal of Psychopharmacology June 19, 2025
- Multimodal predictors of response to intravenous ketamine in treatment-resistant depression: toward personalized treatment in major depressive and bipolar disorders. CNS Spectrums September 28, 2026
and 3 more in the library
Cites 21
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- The salience network is responsible for switching between the default mode network and the central executive network: Replication from DCM Neuroimage May 24, 2014
- Glutamate and the Neural Basis of the Subjective Effects of Ketamine Archives of General Psychiatry February 1, 2008
- The use of ketamine as an antidepressant: a systematic review and meta‐analysis Human Psychopharmacology: Clinical and Experimental April 7, 2015
and 16 more in the library