Cited by 147Functional Brain Connectivity StudiesAnesthesia and Sedative AgentsPain Management and Placebo Effect

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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

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Niesters, Marieke, Khalili-Mahani, Najmeh, Martini, Christian, Aarts, Leon, van Gerven, Joop, van Buchem, Mark A., Dahan, Albert, Rombouts, Serge·2012·Anesthesiology

DOI 10.1097/aln.0b013e31826a0db3

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Abstract

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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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)
ORCID: Niesters, Marieke
Dahan, Albert
Rombouts, Serge
Venue: Anesthesiology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2012-10-01
Volume: 117
Issue: 4
Pages: 868-877
ISSN: 0003-3022 (ISSN-L)
DOI: 10.1097/aln.0b013e31826a0db3
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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Effect of Subanesthetic Ketamine on Intrinsic Functional Brain Connectivity: A Placebo-controlled Functional Magnetic Resonance Imaging Study in Healthy Male Volunteers

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