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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.
Anesthesiology 2012; 117(4):868-77A

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.

Authors+Show Affiliations

Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22890117

Citation

Niesters, Marieke, et al. "Effect of Subanesthetic Ketamine On Intrinsic Functional Brain Connectivity: a Placebo-controlled Functional Magnetic Resonance Imaging Study in Healthy Male Volunteers." Anesthesiology, vol. 117, no. 4, 2012, pp. 868-77.
Niesters M, Khalili-Mahani N, Martini C, et al. Effect of subanesthetic ketamine on intrinsic functional brain connectivity: a placebo-controlled functional magnetic resonance imaging study in healthy male volunteers. Anesthesiology. 2012;117(4):868-77.
Niesters, M., Khalili-Mahani, N., Martini, C., Aarts, L., van Gerven, J., van Buchem, M. A., ... Rombouts, S. (2012). Effect of subanesthetic ketamine on intrinsic functional brain connectivity: a placebo-controlled functional magnetic resonance imaging study in healthy male volunteers. Anesthesiology, 117(4), pp. 868-77.
Niesters M, et al. Effect of Subanesthetic Ketamine On Intrinsic Functional Brain Connectivity: a Placebo-controlled Functional Magnetic Resonance Imaging Study in Healthy Male Volunteers. Anesthesiology. 2012;117(4):868-77. PubMed PMID: 22890117.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of subanesthetic ketamine on intrinsic functional brain connectivity: a placebo-controlled functional magnetic resonance imaging study in healthy male volunteers. AU - Niesters,Marieke, AU - Khalili-Mahani,Najmeh, AU - Martini,Christian, AU - Aarts,Leon, AU - van Gerven,Joop, AU - van Buchem,Mark A, AU - Dahan,Albert, AU - Rombouts,Serge, PY - 2012/8/15/entrez PY - 2012/8/15/pubmed PY - 2012/12/10/medline SP - 868 EP - 77 JF - Anesthesiology JO - Anesthesiology VL - 117 IS - 4 N2 - 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. SN - 1528-1175 UR - https://www.unboundmedicine.com/medline/citation/22890117/Effect_of_subanesthetic_ketamine_on_intrinsic_functional_brain_connectivity:_a_placebo_controlled_functional_magnetic_resonance_imaging_study_in_healthy_male_volunteers_ L2 - http://anesthesiology.pubs.asahq.org/article.aspx?doi=10.1097/ALN.0b013e31826a0db3 DB - PRIME DP - Unbound Medicine ER -