Species-conserved reconfigurations of brain network topology induced by ketamine.
Species-conserved (intermediate) phenotypes that can be quantified and compared across species offer important advantages for translational research and drug discovery. Here, we investigate the utility of network science methods to assess the pharmacological alterations of the large-scale architecture of brain networks in rats and humans. In a double-blind, placebo-controlled, cross-over study in humans and a placebo-controlled two-group study in rats, we demonstrate that the application of ketamine leads to a topological reconfiguration of large-scale brain networks towards less-integrated and more-segregated information processing in both the species. As these alterations are opposed to those commonly observed in patients suffering from depression, they might indicate systems-level correlates of the antidepressant effect of ketamine.
Research Group Translational Imaging, Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
R
R
Becker
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
U
U
Braun
Tailored Therapeutics Neuroscience, Eli Lilly and Company, Indianapolis, IN, USA.|Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA.|Department of Radiology and Imaging Sciences, Indiana University, Indianapolis, IN, USA.
A J
AJ
Schwarz
Research Group Translational Imaging, Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
N
N
Gass
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
J I
JI
Schweiger
Research Group Translational Imaging, Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
W
W
Weber-Fahr
Neuropsychiatry Pole of Therapeutic Innovation, Institut de Recherches Servier, Croissy-sur-Seine, France.
E
E
Schenker
Spedding Research Solutions, Paris, France.
M
M
Spedding
Research Group Translational Imaging, Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.|Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
C
C
Clemm von Hohenberg
CNS Biomarker, Pharmaceuticals Division, F. Hoffmann-La Roche, Basel, Switzerland.
C
C
Risterucci
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Z
Z
Zang
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
O
O
Grimm
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
H
H
Tost
Research Group Translational Imaging, Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.|Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
A
A
Sartorius
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
A
A
Meyer-Lindenberg
D000328:Adult; D000818:Animals; D001921:Brain / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine