Ketamine modulates subgenual cingulate connectivity with the memory-related neural circuit-a mechanism of relevance to resistant depression?
Jing J Wong, Owen O'Daly, Mitul A. Mehta, Allan H. Young, James Stone
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study (within-subject resting-state fMRI) Peer reviewed |
|---|---|
| Sample size | 13 |
| Population | Right-handed healthy male subjects |
| Intervention | Ketamine |
| Dose | target blood level = 150 ng/ml |
| Duration | 15 min resting-state fMRI with infusion starting at 5 min |
| Topics | Depression Ketamine Esketamine |
| Keywords | Anterior cingulate Antidepressant MRI |
| Key findings | During intravenous ketamine infusion, functional connectivity between the subgenual anterior cingulate cortex and regions including the brainstem, hippocampus, parahippocampal gyrus, retrosplenial cortex, and thalamus shifted to negative correlation, whereas before infusion the sgACC was positively coupled with the anterior cingulate and negatively coupled with the anterior cerebellum. The authors suggest this reduced connectivity may mediate ketamine's antidepressant effects, but state that further work is required to test the hypothesis. |
Abstract
Background. Ketamine has been reported to have efficacy as an antidepressant in several studies of treatment-resistant depression. In this study, we investigate whether an acute administration of ketamine leads to reductions in the functional connectivity of subgenual anterior cingulate cortex (sgACC) with other brain regions. Methods. Thirteen right-handed healthy male subjects underwent a 15 min resting state fMRI with an infusion of intravenous ketamine (target blood level = 150 ng/ml) starting at 5 min. We used a seed region centred on the sgACC and assessed functional connectivity before and during ketamine administration. Results. Before ketamine administration, positive coupling with the sgACC seed region was observed in a large cluster encompassing the anterior cingulate and negative coupling was observed with the anterior cerebellum. Following ketamine administration, sgACC activity became negatively correlated with the brainstem, hippocampus, parahippocampal gyrus, retrosplenial cortex, and thalamus. Discussion. Ketamine reduced functional connectivity of the sgACC with brain regions implicated in emotion, memory and mind wandering. It is possible the therapeutic effects of ketamine may be mediated via this mechanism, although further work is required to test this hypothesis.
Comparable studies
Other experimental studies on ketamine for depression, most cited first.
Citations in the library
Cited by 16
- Ketamine: 50 Years of Modulating the Mind Frontiers in Human Neuroscience November 29, 2016
- Molecular and cellular mechanisms underlying the antidepressant effects of ketamine enantiomers and its metabolites Translational Psychiatry November 7, 2019
- Decreased directed functional connectivity in the psychedelic state. Neuroimage December 17, 2019
- The anterior cingulate cortex as a key locus of ketamine’s antidepressant action Neuroscience & Biobehavioral Reviews May 10, 2021
- The neurophysiology of ketamine: an integrative review Reviews in the Neurosciences May 5, 2020
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Cites 6
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Glutamate and the Neural Basis of the Subjective Effects of Ketamine Archives of General Psychiatry February 1, 2008
- Ketamine Decreases Resting State Functional Network Connectivity in Healthy Subjects: Implications for Antidepressant Drug Action PLoS One September 24, 2012
- Neural correlates of rapid antidepressant response to ketamine in bipolar disorder Bipolar Disorders September 18, 2013
- Ketamine induces a robust whole-brain connectivity pattern that can be differentially modulated by drugs of different mechanism and clinical profile Psychopharmacology May 19, 2015
and 1 more in the library