Brain Structure and Function

, Volume 222, Issue 3, pp 1533–1542 | Cite as

Ketamine-dependent neuronal activation in healthy volunteers

  • Anna Höflich
  • Andreas Hahn
  • Martin Küblböck
  • Georg S. Kranz
  • Thomas Vanicek
  • Sebastian Ganger
  • Marie Spies
  • Christian Windischberger
  • Siegfried Kasper
  • Dietmar Winkler
  • Rupert Lanzenberger
Original Article


Over the last years, a number of studies have been conducted to clarify the neurobiological correlates of ketamine application. However, comprehensive information regarding the influence of ketamine on cortical activity is still lacking. Using resting-state functional MRI and integrating pharmacokinetic information, a double-blind, randomized, placebo-controlled, crossover study was performed to determine the effects of ketamine on neuronal activation. During a 55 min resting-state fMRI scan, esketamine (Ketanest S®) was administered intravenously to 35 healthy volunteers. Neural activation as indicated by the BOLD signal using the pharmacokinetic curve of ketamine plasma levels as a regressor was computed. Compared with placebo, ketamine-dependent increases of neural activation were observed in the midcingulate cortex, the dorsal part of the anterior cingulate cortex, the insula bilaterally, and the thalamus (t values ranging between 5.95–9.78, p < 0.05; FWE-corrected). A significant decrease of neural activation in the ketamine condition compared to placebo was found in a cluster within the subgenual/subcallosal part of the anterior cingulate cortex, the orbitofrontal cortex and the gyrus rectus (t = 7.81, p < 0.05, FWE-corrected). Using an approach combining pharmacological and fMRI data, important information about the neurobiological correlates of the clinical antidepressant effects of ketamine could be revealed.


Ketamine fMRI Anterior cingulate gyrus Insula Thalamus 



This work was supported by the Austrian National Bank (Grant Number P 14193). The authors thank the staff of the Department of Psychiatry and Psychotherapy and the MRI center for their technical and medical support; to Pia Baldinger for support in the management of the study and Natalia Lipskaia for her contribution in the clinical performance.

Compliance with ethical standards

Conflict of interest

Dr. Kasper has received grant/research support from Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Lundbeck, Pfizer, and Servier; he has served as a consultant or on advisory boards for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Lundbeck, Novartis, Pfizer, Schwabe, and Servier; and he has served on speakers’ bureaus for Angelini, AOP Orphan Pharmaceuticals AG, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Lundbeck, Neuraxpharm, Pfizer, Pierre Fabre, Schwabe, and Servier. R. Lanzenberger received travel grants and/or conference speaker honoraria from AstraZeneca, Lundbeck A/S, Dr. Willmar Schwabe GmbH, Orphan Pharmaceuticals AG, Janssen-Cilag Pharma GmbH, and Roche Austria GmbH. D. Winkler has received lecture fees from Bristol-Myers Squibb, CSC Pharmaceuticals, Novartis, Pfizer, and Servier.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Anna Höflich
    • 1
  • Andreas Hahn
    • 1
  • Martin Küblböck
    • 2
  • Georg S. Kranz
    • 1
  • Thomas Vanicek
    • 1
  • Sebastian Ganger
    • 1
  • Marie Spies
    • 1
  • Christian Windischberger
    • 2
  • Siegfried Kasper
    • 1
  • Dietmar Winkler
    • 1
  • Rupert Lanzenberger
    • 1
  1. 1.Department of Psychiatry and PsychotherapyMedical University of ViennaViennaAustria
  2. 2.MR Center of Excellence, Center for Medical Physics and Biomedical EngineeringMedical University of ViennaViennaAustria

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