Ketamine induced changes in regional cerebral blood flow, interregional connectivity patterns, and glutamate metabolism.
Adult
Cerebrovascular Circulation
/ drug effects
Excitatory Amino Acid Antagonists
/ pharmacology
Female
Glutamic Acid
/ drug effects
Gyrus Cinguli
/ diagnostic imaging
Hippocampus
/ diagnostic imaging
Humans
Ketamine
/ pharmacology
Magnetic Resonance Spectroscopy
Male
Nerve Net
/ diagnostic imaging
Putamen
/ diagnostic imaging
Young Adult
Journal
Journal of psychiatric research
ISSN: 1879-1379
Titre abrégé: J Psychiatr Res
Pays: England
ID NLM: 0376331
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
17
04
2019
revised:
19
06
2019
accepted:
26
07
2019
pubmed:
4
8
2019
medline:
15
9
2020
entrez:
4
8
2019
Statut:
ppublish
Résumé
Several imaging studies have attempted to characterize the contribution of glutamatergic dysfunction to functional dysconnectivity of large-scale brain networks using ketamine models. However, findings from BOLD imaging studies are conflicting, in part because the signal stems from a complex interaction between blood flow, blood volume, and oxygen consumption. We used arterial spin labelling imaging to measure regional cerebral blood flow (rCBF) in a group of healthy volunteers during a saline and during a ketamine infusion. We examined changes in rCBF and interregional connectivity patterns, as well as their associations with clinical symptom severity and Glx (glutamate + glutamine) assessed with magnetic resonance spectroscopy. We report a regionally selective pattern of rCBF changes following ketamine administration and complex changes in interregional connectivity patterns. We also found that the increase in rCBF in the bilateral putamen and left hippocampus was positively correlated with ketamine induced clinical symptom severity while anterior cingulate rCBF during the ketamine challenge was negatively correlated with change in hippocampal Glx. Our study adds to the efforts to empirically confirm putative links between an NMDA receptor blockage and dysconnectivity of large-scale brain networks, specifically the salience, executive control and default mode networks, suggesting that a glutamatergic imbalance may contribute to dysconnectivity. Development of glutamatergic compounds that alleviate disease burden, possibly through normalizing glutamate excess related increased rCBF, is direly needed.
Identifiants
pubmed: 31376621
pii: S0022-3956(19)30481-9
doi: 10.1016/j.jpsychires.2019.07.008
pmc: PMC7291620
mid: NIHMS1536675
pii:
doi:
Substances chimiques
Excitatory Amino Acid Antagonists
0
Glutamic Acid
3KX376GY7L
Ketamine
690G0D6V8H
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108-115Subventions
Organisme : NIMH NIH HHS
ID : K23 MH106683
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.
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