Cargando…
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()
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-hypothes...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6040604/ https://www.ncbi.nlm.nih.gov/pubmed/30003027 http://dx.doi.org/10.1016/j.nicl.2018.05.037 |
_version_ | 1783338869378252800 |
---|---|
author | Mueller, Felix Musso, Francesco London, Markus de Boer, Peter Zacharias, Norman Winterer, Georg |
author_facet | Mueller, Felix Musso, Francesco London, Markus de Boer, Peter Zacharias, Norman Winterer, Georg |
author_sort | Mueller, Felix |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6040604 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-60406042018-07-12 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() Mueller, Felix Musso, Francesco London, Markus de Boer, Peter Zacharias, Norman Winterer, Georg Neuroimage Clin Regular Article 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. Elsevier 2018-06-01 /pmc/articles/PMC6040604/ /pubmed/30003027 http://dx.doi.org/10.1016/j.nicl.2018.05.037 Text en © 2018 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Regular Article Mueller, Felix Musso, Francesco London, Markus de Boer, Peter Zacharias, Norman Winterer, Georg 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() |
title | 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() |
title_full | 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() |
title_fullStr | 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() |
title_full_unstemmed | 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() |
title_short | 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() |
title_sort | 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() |
topic | Regular Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6040604/ https://www.ncbi.nlm.nih.gov/pubmed/30003027 http://dx.doi.org/10.1016/j.nicl.2018.05.037 |
work_keys_str_mv | AT muellerfelix pharmacologicalfmrieffectsofsubanestheticketamineonrestingstatefunctionalconnectivityinthedefaultmodenetworksaliencenetworkdorsalattentionnetworkandexecutivecontrolnetwork AT mussofrancesco pharmacologicalfmrieffectsofsubanestheticketamineonrestingstatefunctionalconnectivityinthedefaultmodenetworksaliencenetworkdorsalattentionnetworkandexecutivecontrolnetwork AT londonmarkus pharmacologicalfmrieffectsofsubanestheticketamineonrestingstatefunctionalconnectivityinthedefaultmodenetworksaliencenetworkdorsalattentionnetworkandexecutivecontrolnetwork AT deboerpeter pharmacologicalfmrieffectsofsubanestheticketamineonrestingstatefunctionalconnectivityinthedefaultmodenetworksaliencenetworkdorsalattentionnetworkandexecutivecontrolnetwork AT zachariasnorman pharmacologicalfmrieffectsofsubanestheticketamineonrestingstatefunctionalconnectivityinthedefaultmodenetworksaliencenetworkdorsalattentionnetworkandexecutivecontrolnetwork AT winterergeorg pharmacologicalfmrieffectsofsubanestheticketamineonrestingstatefunctionalconnectivityinthedefaultmodenetworksaliencenetworkdorsalattentionnetworkandexecutivecontrolnetwork |