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Effect of Subanesthetic Ketamine on Intrinsic Functional Brain Connectivity: A Placebo-controlled Functional Magnetic Resonance Imaging Study in Healthy Male Volunteers
Open accessAbstract
Background: The influence of psychoactive drugs on the central nervous system has been investigated with positron emission tomography and task-related functional magnetic resonance imaging. However, it is not known how these drugs affect the intrinsic large-scale interactions of the brain (resting-state functional magnetic resonance imaging connectivity). In this study, the effect of low-dose S(+)-ketamine on intrinsic brain connectivity was investigated. Methods: Twelve healthy, male volunteers received a 2-h intravenous S(+)-ketamine infusion (first hour 20 mg/70 kg, second hour 40 mg/70 kg). Before, during, and after S(+)-ketamine administration, resting-state brain connectivity was measured. In addition, heat pain tests were performed between imaging sessions to determine ketamine-induced analgesia. A mixed-effects general linear model was used to determine drug and pain effects on resting-state brain connectivity. Results: Ketamine increased the connectivity most importantly in the cerebellum and visual cortex in relation to the medial visual network. A decrease in connectivity was observed in the auditory and somatosensory network in relation to regions responsible for pain sensing and the affective processing of pain, which included the amygdala, insula, and anterior cingulate cortex. Connectivity variations related to fluctuations in pain scores were observed in the anterior cingulate cortex, insula, orbitofrontal cortex, and the brainstem, regions involved in descending inhibition of pain. Conclusions: Changes in connectivity were observed in the areas that explain ketamine's pharmacodynamic profile with respect to analgesia and psychedelic and other side effects. In addition, pain and ketamine changed brain connectivity in areas involved in endogenous pain modulation.
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“ketamine counters the hyper-excitatory state present in ascending pain circuitry through NMDAR inhibition while also enhancing the activity of brain regions involved in top-down inhibition of pain centers such as the PFC and brainstem (Niesters et al., 2012).”
From Mechanisms of ketamine and its metabolites as antidepressants (2022) · cites this paper as Niesters et al., 2012
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Advances in functional and structural MR image analysis and implementation as FSL
Smith, S. M., Jenkinson, M., Woolrich, M. W., Beckmann, C. F., Behrens, T. E. J., Johansen-Berg, H., Bannister, P. R., De Luca, M., Drobnjak, I., Flitney, D. E., et al. (2004) · NeuroImage · doi:10.1016/j.neuroimage.2004.07.051 · Cited by 13,630
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Correspondence of the brain's functional architecture during activation and rest
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Consistent resting-state networks across healthy subjects
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Self-citationInvestigations into resting-state connectivity using independent component analysis
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Toward discovery science of human brain function
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Self-citationOssipov, M. H., Dussor, G. O., & Porreca, F. (2010) · Journal of Clinical Investigation · doi:10.1172/jci43766 · Cited by 1,234
Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin
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Activation of the Opioidergic Descending Pain Control System Underlies Placebo Analgesia
Eippert, F., Bingel, U., Schoell, E. D., Yacubian, J., Klinger, R., Lorenz, J., & Büchel, C. (2009) · Neuron · doi:10.1016/j.neuron.2009.07.014 · Cited by 839
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Schwenk, E. S., Viscusi, E. R., Buvanendran, A., Hurley, R. W., Wasan, A. D., Narouze, S., Bhatia, A., Davis, F. N., Hooten, W. M., & Cohen, S. P. (2018) · Regional Anesthesia & Pain Medicine · doi:10.1097/aap.0000000000000806 · Cited by 628
Ketamine for chronic pain: risks and benefits
Niesters, M., Martini, C., & Dahan, A. (2013) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12094 · Cited by 526
Self-citationResting-State Functional MR Imaging: A New Window to the Brain
Barkhof, F., Haller, S., & Rombouts, S. A. R. B. (2014) · Radiology · doi:10.1148/radiol.14132388 · Cited by 397
Self-citationReviewing the ketamine model for schizophrenia
Frohlich, J., & Van Horn, J. D. (2014) · Journal of Psychopharmacology · doi:10.1177/0269881113512909 · Cited by 303
Ketamine use in current clinical practice
Gao, M., Rejaei, D., & Liu, H. (2016) · Acta Pharmacologica Sinica · doi:10.1038/aps.2016.5 · Cited by 286
Metadata
- Authors
- Niesters, M., Khalili-Mahani, N., Martini, C., Aarts, L., van Gerven, J., van Buchem, M. A., Dahan, A., & Rombouts, S.
- Affiliations
- PhD Student.
- Senior Research Associate.
- PhD Student, Resident.
- Leiden University Medical Center (NL)
- Professor, Department of Neurology, Leiden University Medical Center, and Center for Human Drug Research, Leiden, The Netherlands.
- Professor, Leiden Institute for Brain and Cognition (LIBC) and Department of Radiology, Leiden University Medical Center.
- Leiden University (NL)
- Venue
- Anesthesiology
- Published
- 2012-10-01
- Volume
- 117
- Issue
- 4
- Pages
- 868-877
- ISSN
- 0003-3022 (ISSN-L)
- OpenAlex
- W2056836466
- Cited by
- 147
- References
- 50
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 6 · 2023: 9 · 2022: 4 · 2021: 12 · 2020: 17 · 2019: 14 · 2018: 12 · 2017: 11 · 2016: 13 · 2015: 18 · 2014: 10 · 2013: 10
- FWCI
- 6.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Anesthesiology (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
- Keywords
- subanesthetic ketamine, resting-state functional connectivity, intrinsic brain connectivity, ketamine analgesia, pain modulation, cerebellum, visual cortex, anterior cingulate cortex, insula, amygdala, descending pain inhibition, psychedelic effects, ketamine side effects
- MeSH terms
- Adult, Anesthetics, Dissociative, Brain, Data Interpretation, Statistical, Hallucinogens, Hot Temperature, Humans, Image Processing, Computer-Assisted, Injections, Intravenous, Ketamine, Magnetic Resonance Imaging, Male, Nerve Net, Pain, Pain Measurement, Linear Models, Single-Blind Method, Young Adult
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