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Ketamine Modulates Hippocampal Neurochemistry and Functional Connectivity – A Combined Magnetic Resonance Spectroscopy and Resting State fMRI Study in Healthy Volunteers
A growing body of evidence suggests glutamate excess in schizophrenia and that N-methyl-d-aspartate receptor (NMDAR) hypofunction on γ-aminobutyric acid (GABA) interneurons disinhibiting pyramidal cells may be relevant to this hyperglutamatergic state. To better understand how NMDAR hypofunction aff...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562151/ https://www.ncbi.nlm.nih.gov/pubmed/27480494 http://dx.doi.org/10.1038/mp.2016.122 |
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author | Kraguljac, Nina V. Frölich, Michael A. Tran, Steve White, David M. Nichols, Nona Barton-McArdle, Alexander Reid, Meredith A. Bolding, Mark S. Lahti, Adrienne C. |
author_facet | Kraguljac, Nina V. Frölich, Michael A. Tran, Steve White, David M. Nichols, Nona Barton-McArdle, Alexander Reid, Meredith A. Bolding, Mark S. Lahti, Adrienne C. |
author_sort | Kraguljac, Nina V. |
collection | PubMed |
description | A growing body of evidence suggests glutamate excess in schizophrenia and that N-methyl-d-aspartate receptor (NMDAR) hypofunction on γ-aminobutyric acid (GABA) interneurons disinhibiting pyramidal cells may be relevant to this hyperglutamatergic state. To better understand how NMDAR hypofunction affects the brain, we used Magnetic Resonance Spectroscopy and resting state functional MRI to study the effects of ketamine on hippocampal neurometabolite levels and functional connectivity in 15 healthy human subjects. We observed a ketamine induced increase of hippocampal Glx (glutamate+glutamine; F= 3.76; p= 0.04), a decrease in fronto-temporal (t=4.92, p(FDR)< .05, k(E)= 2198, x= -30, y= 52, z= 14) and temporo-parietal functional connectivity (t=5.07, p(FDR)< .05, k(E)= 6094, x= -28, y= -36, z= -2), and a possible link between connectivity changes and elevated Glx. Our data empirically support that hippocampal glutamatergic elevation and resting state network alterations may arise from NMDAR hypofunction and establish a proof of principle whereby experimental modelling of a disorder can help mechanistically integrate distinct neuroimaging abnormalities in schizophrenia. |
format | Online Article Text |
id | pubmed-5562151 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
record_format | MEDLINE/PubMed |
spelling | pubmed-55621512017-08-21 Ketamine Modulates Hippocampal Neurochemistry and Functional Connectivity – A Combined Magnetic Resonance Spectroscopy and Resting State fMRI Study in Healthy Volunteers Kraguljac, Nina V. Frölich, Michael A. Tran, Steve White, David M. Nichols, Nona Barton-McArdle, Alexander Reid, Meredith A. Bolding, Mark S. Lahti, Adrienne C. Mol Psychiatry Article A growing body of evidence suggests glutamate excess in schizophrenia and that N-methyl-d-aspartate receptor (NMDAR) hypofunction on γ-aminobutyric acid (GABA) interneurons disinhibiting pyramidal cells may be relevant to this hyperglutamatergic state. To better understand how NMDAR hypofunction affects the brain, we used Magnetic Resonance Spectroscopy and resting state functional MRI to study the effects of ketamine on hippocampal neurometabolite levels and functional connectivity in 15 healthy human subjects. We observed a ketamine induced increase of hippocampal Glx (glutamate+glutamine; F= 3.76; p= 0.04), a decrease in fronto-temporal (t=4.92, p(FDR)< .05, k(E)= 2198, x= -30, y= 52, z= 14) and temporo-parietal functional connectivity (t=5.07, p(FDR)< .05, k(E)= 6094, x= -28, y= -36, z= -2), and a possible link between connectivity changes and elevated Glx. Our data empirically support that hippocampal glutamatergic elevation and resting state network alterations may arise from NMDAR hypofunction and establish a proof of principle whereby experimental modelling of a disorder can help mechanistically integrate distinct neuroimaging abnormalities in schizophrenia. 2016-08-02 2017-04 /pmc/articles/PMC5562151/ /pubmed/27480494 http://dx.doi.org/10.1038/mp.2016.122 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Kraguljac, Nina V. Frölich, Michael A. Tran, Steve White, David M. Nichols, Nona Barton-McArdle, Alexander Reid, Meredith A. Bolding, Mark S. Lahti, Adrienne C. Ketamine Modulates Hippocampal Neurochemistry and Functional Connectivity – A Combined Magnetic Resonance Spectroscopy and Resting State fMRI Study in Healthy Volunteers |
title | Ketamine Modulates Hippocampal Neurochemistry and Functional Connectivity – A Combined Magnetic Resonance Spectroscopy and Resting State fMRI Study in Healthy Volunteers |
title_full | Ketamine Modulates Hippocampal Neurochemistry and Functional Connectivity – A Combined Magnetic Resonance Spectroscopy and Resting State fMRI Study in Healthy Volunteers |
title_fullStr | Ketamine Modulates Hippocampal Neurochemistry and Functional Connectivity – A Combined Magnetic Resonance Spectroscopy and Resting State fMRI Study in Healthy Volunteers |
title_full_unstemmed | Ketamine Modulates Hippocampal Neurochemistry and Functional Connectivity – A Combined Magnetic Resonance Spectroscopy and Resting State fMRI Study in Healthy Volunteers |
title_short | Ketamine Modulates Hippocampal Neurochemistry and Functional Connectivity – A Combined Magnetic Resonance Spectroscopy and Resting State fMRI Study in Healthy Volunteers |
title_sort | ketamine modulates hippocampal neurochemistry and functional connectivity – a combined magnetic resonance spectroscopy and resting state fmri study in healthy volunteers |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562151/ https://www.ncbi.nlm.nih.gov/pubmed/27480494 http://dx.doi.org/10.1038/mp.2016.122 |
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