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Pharmacological fMRI: Effects of subanesthetic ketamine on resting-state functional connectivity in the default mode network, salience network, dorsal attention network and executive control network.
Neuroimage Clin 2018; 19:745-757NC

Abstract

Background

Subanesthetic dosages of the NMDAR antagonist, S-Ketamine, can cause changes in behavior in healthy subjects, which are similar to the state acute psychosis and are relevant in translational schizophrenia research. Functional magnetic resonance imaging (fMRI) can be used for non-hypothesis-driven analysis of brain connectivity. The correlation between clinical behavioral scores and neuroimaging can help to characterize ketamine effects on healthy brains in resting state.

Method

seventeen healthy, male subjects (mean: 27.42 years, SD: 4.42) were administered an infusion with S-Ketamine (initial bolus 1 mg/kg and continuous infusion of 0.015625 mg/kg/min with dosage reduction -10%/10 min) or saline in a randomized, double-blind, cross-over study. During infusion, resting state connectivity was measured and analyzed with a seed-to-voxel fMRI analysis approach. The seed regions were located in the posterior cingulate cortex, intraparietal sulcus, dorsolateral prefrontal cortex and fronto-insular cortex. Receiver operating characteristics (ROC) were calculated to assess the accuracy of the ketamine-induced functional connectivity changes. Bivariate Pearson correlation was used for correlation testing of functional connectivity changes with changes of clinical scores (PANSS, 5D-ASC).

Results

In the executive network (ECN), ketamine significantly increases the functional connectivity with parts of the anterior cingulum and superior frontal gyrus, but no significant correlations with clinical symptoms were found. Decreased connectivity between the salience network (SN) and the calcarine fissure was found, which is significantly correlated with negative symptoms (PANSS) (R2 > 0.4).

Conclusion

Decreased ketamine-induced functional connectivity in the salience network may qualify as accurate and highly predictive biomarkers for ketamine induced negative symptoms.

Authors+Show Affiliations

Experimental and Clinical Research Center (ECRC), Dept. of Anesthesiology and Intensive Care Medicine, Charité - University Medicine Berlin, Germany. Electronic address: felix.mueller@charite.de.Department of Psychiatry, Heinrich-Heine University, Düsseldorf, Germany.Janssen-Cilag GmbH, Early Development and Clinical Pharmacology, Neuss, Germany.Janssen Pharmaceutica, Johnson & Johnson Pharmaceutical Research and Development, Beerse, Belgium.Experimental and Clinical Research Center (ECRC), Dept. of Anesthesiology and Intensive Care Medicine, Charité - University Medicine Berlin, Germany.Experimental and Clinical Research Center (ECRC), Dept. of Anesthesiology and Intensive Care Medicine, Charité - University Medicine Berlin, Germany; Pharmaimage Biomarker Solutions GmbH, Berlin, Germany; Pharmaimage Biomarker Solutions Inc., Boston, USA.

Pub Type(s)

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

Language

eng

PubMed ID

30003027

Citation

Mueller, Felix, et al. "Pharmacological fMRI: Effects of Subanesthetic Ketamine On Resting-state Functional Connectivity in the Default Mode Network, Salience Network, Dorsal Attention Network and Executive Control Network." NeuroImage. Clinical, vol. 19, 2018, pp. 745-757.
Mueller F, Musso F, London M, et al. Pharmacological fMRI: Effects of subanesthetic ketamine on resting-state functional connectivity in the default mode network, salience network, dorsal attention network and executive control network. Neuroimage Clin. 2018;19:745-757.
Mueller, F., Musso, F., London, M., de Boer, P., Zacharias, N., & Winterer, G. (2018). Pharmacological fMRI: Effects of subanesthetic ketamine on resting-state functional connectivity in the default mode network, salience network, dorsal attention network and executive control network. NeuroImage. Clinical, 19, pp. 745-757. doi:10.1016/j.nicl.2018.05.037.
Mueller F, et al. Pharmacological fMRI: Effects of Subanesthetic Ketamine On Resting-state Functional Connectivity in the Default Mode Network, Salience Network, Dorsal Attention Network and Executive Control Network. Neuroimage Clin. 2018;19:745-757. PubMed PMID: 30003027.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacological fMRI: Effects of subanesthetic ketamine on resting-state functional connectivity in the default mode network, salience network, dorsal attention network and executive control network. AU - Mueller,Felix, AU - Musso,Francesco, AU - London,Markus, AU - de Boer,Peter, AU - Zacharias,Norman, AU - Winterer,Georg, Y1 - 2018/06/01/ PY - 2018/02/19/received PY - 2018/05/13/revised PY - 2018/05/30/accepted PY - 2018/7/14/entrez PY - 2018/7/14/pubmed PY - 2019/1/22/medline KW - Correlation testing KW - Cross-over fMRI study KW - Resting-state fMRI KW - Seed-to-voxel fMRI analysis KW - Subanesthetic ketamine effects SP - 745 EP - 757 JF - NeuroImage. Clinical JO - Neuroimage Clin VL - 19 N2 - Background: Subanesthetic dosages of the NMDAR antagonist, S-Ketamine, can cause changes in behavior in healthy subjects, which are similar to the state acute psychosis and are relevant in translational schizophrenia research. Functional magnetic resonance imaging (fMRI) can be used for non-hypothesis-driven analysis of brain connectivity. The correlation between clinical behavioral scores and neuroimaging can help to characterize ketamine effects on healthy brains in resting state. Method: seventeen healthy, male subjects (mean: 27.42 years, SD: 4.42) were administered an infusion with S-Ketamine (initial bolus 1 mg/kg and continuous infusion of 0.015625 mg/kg/min with dosage reduction -10%/10 min) or saline in a randomized, double-blind, cross-over study. During infusion, resting state connectivity was measured and analyzed with a seed-to-voxel fMRI analysis approach. The seed regions were located in the posterior cingulate cortex, intraparietal sulcus, dorsolateral prefrontal cortex and fronto-insular cortex. Receiver operating characteristics (ROC) were calculated to assess the accuracy of the ketamine-induced functional connectivity changes. Bivariate Pearson correlation was used for correlation testing of functional connectivity changes with changes of clinical scores (PANSS, 5D-ASC). Results: In the executive network (ECN), ketamine significantly increases the functional connectivity with parts of the anterior cingulum and superior frontal gyrus, but no significant correlations with clinical symptoms were found. Decreased connectivity between the salience network (SN) and the calcarine fissure was found, which is significantly correlated with negative symptoms (PANSS) (R2 > 0.4). Conclusion: Decreased ketamine-induced functional connectivity in the salience network may qualify as accurate and highly predictive biomarkers for ketamine induced negative symptoms. SN - 2213-1582 UR - https://www.unboundmedicine.com/medline/citation/30003027/Pharmacological_fMRI:_Effects_of_subanesthetic_ketamine_on_resting_state_functional_connectivity_in_the_default_mode_network_salience_network_dorsal_attention_network_and_executive_control_network_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2213-1582(18)30183-9 DB - PRIME DP - Unbound Medicine ER -