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, A Henning, Simone Grimm
European Archives of Psychiatry and Clinical Neuroscience January 12, 2022 DOI: 10.1007/s00406-021-01377-2 via OpenAlex
Summary
Ketamine's rapid antidepressant effects involve the glutamatergic system. A multimodal imaging study of 23 healthy volunteers used resting state fMRI and proton magnetic resonance spectroscopy to examine links between metabolic and functional brain changes during intravenous ketamine infusion. The pregenual anterior cingulate cortex (pgACC) was the focus. Functional connectivity changed 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. Stronger pgACC activation during ketamine was linked to lower glutamine concentration, and reduced connectivity between pgACC and aMCC was related to increased pgACC activation and reduced glutamine.
Study at a glance
| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 23 |
| Population | Healthy volunteers |
| Intervention | Ketamine |
| Topics | Ketamine |
| Keywords | Anterior cingulate cortex Glutamine Glutamate receptor Neuroscience |
| Citations | 13 |
| Key finding | 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.