Skip to main content
SpringerLink
Log in

Ketamine-dependent neuronal activation in healthy volunteers

  • Original Article
  • Published:
Brain Structure and Function Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • aan het Rot M, Collins KA, Murrough JW, Perez AM, Reich DL, Charney DS, Mathew SJ (2010) Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression. Biol Psychiatry 67(2):139–145

    Article  CAS  PubMed  Google Scholar 

  • Abdallah CG, Averill LA, Krystal JH (2015) Ketamine as a promising prototype for a new generation of rapid-acting antidepressants. Ann N Y Acad Sci 1344:66–77

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Anticevic A, Corlett PR, Cole MW, Savic A, Gancsos M, Tang Y, Repovs G, Murray JD, Driesen NR, Morgan PT, Xu K, Wang F, Krystal JH (2015) N-methyl-d-aspartate receptor antagonist effects on prefrontal cortical connectivity better model early than chronic schizophrenia. Biol Psychiatry 77(6):569–580

    Article  CAS  PubMed  Google Scholar 

  • Aroni F, Iacovidou N, Dontas I, Pourzitaki C, Xanthos T (2009) Pharmacological aspects and potential new clinical applications of ketamine: reevaluation of an old drug. J Clin Pharmacol 49(8):957–964

    Article  CAS  PubMed  Google Scholar 

  • Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH (2000) Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 47(4):351–354

    Article  CAS  PubMed  Google Scholar 

  • Borsook D, Becerra L, Hargreaves R (2006) A role for fMRI in optimizing CNS drug development. Nat Rev Drug Discov 5(5):411–424

    Article  CAS  PubMed  Google Scholar 

  • Bustillo JR, Rowland LM, Mullins P, Jung R, Chen H, Qualls C, Hammond R, Brooks WM, Lauriello J (2010) 1H-MRS at 4 tesla in minimally treated early schizophrenia. Mol Psychiatry 15(6):629–636

    Article  CAS  PubMed  Google Scholar 

  • Dandash O, Harrison BJ, Adapa R, Gaillard R, Giorlando F, Wood SJ, Fletcher PC, Fornito A (2015) Selective augmentation of striatal functional connectivity following NMDA receptor antagonism: implications for psychosis. Neuropsychopharmacology 40(3):622–631

    Article  CAS  PubMed  Google Scholar 

  • De Simoni S, Schwarz AJ, O’Daly OG, Marquand AF, Brittain C, Gonzales C, Stephenson S, Williams SC, Mehta MA (2013) Test–retest reliability of the BOLD pharmacological MRI response to ketamine in healthy volunteers. Neuroimage 64:75–90

    Article  PubMed  Google Scholar 

  • Deakin JF, Lees J, McKie S, Hallak JE, Williams SR, Dursun SM (2008) Glutamate and the neural basis of the subjective effects of ketamine: a pharmaco-magnetic resonance imaging study. Arch Gen Psychiatry 65(2):154–164

    Article  PubMed  Google Scholar 

  • Doyle OM, De Simoni S, Schwarz AJ, Brittain C, O’Daly OG, Williams SC, Mehta MA (2013) Quantifying the attenuation of the ketamine pharmacological magnetic resonance imaging response in humans: a validation using antipsychotic and glutamatergic agents. J Pharmacol Exp Ther 345(1):151–160

    Article  CAS  PubMed  Google Scholar 

  • Drevets WC, Price JL, Simpson JR Jr, Todd RD, Reich T, Vannier M, Raichle ME (1997) Subgenual prefrontal cortex abnormalities in mood disorders. Nature 386(6627):824–827

    Article  CAS  PubMed  Google Scholar 

  • Driesen NR, McCarthy G, Bhagwagar Z, Bloch M, Calhoun V, D’Souza DC, Gueorguieva R, He G, Ramachandran R, Suckow RF, Anticevic A, Morgan PT, Krystal JH (2013) Relationship of resting brain hyperconnectivity and schizophrenia-like symptoms produced by the NMDA receptor antagonist ketamine in humans. Mol Psychiatry 18:1199–1204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • du Jardin KG, Liebenberg N, Muller HK, Elfving B, Sanchez C, Wegener G (2016) Differential interaction with the serotonin system by S-ketamine, vortioxetine, and fluoxetine in a genetic rat model of depression. Psychopharmacology 233(14):2813–2825

    Article  PubMed  Google Scholar 

  • Duman RS, Li N, Liu RJ, Duric V, Aghajanian G (2012) Signaling pathways underlying the rapid antidepressant actions of ketamine. Neuropharmacology 62(1):35–41

    Article  CAS  PubMed  Google Scholar 

  • Franceschini MA, Radhakrishnan H, Thakur K, Wu W, Ruvinskaya S, Carp S, Boas DA (2010) The effect of different anesthetics on neurovascular coupling. Neuroimage 51(4):1367–1377

    Article  PubMed  PubMed Central  Google Scholar 

  • Francois J, Grimm O, Schwarz AJ, Schweiger J, Haller L, Risterucci C, Bohringer A, Zang Z, Tost H, Gilmour G, Meyer-Lindenberg A (2016) Ketamine suppresses the ventral striatal response to reward anticipation: a cross-species translational neuroimaging study. Neuropsychopharmacology 41:1386–1394

    Article  CAS  PubMed  Google Scholar 

  • Geisslinger G, Hering W, Thomann P, Knoll R, Kamp HD, Brune K (1993) Pharmacokinetics and pharmacodynamics of ketamine enantiomers in surgical patients using a stereoselective analytical method. Br J Anaesth 70(6):666–671

    Article  CAS  PubMed  Google Scholar 

  • Gluck MR, Thomas RG, Davis KL, Haroutunian V (2002) Implications for altered glutamate and GABA metabolism in the dorsolateral prefrontal cortex of aged schizophrenic patients. Am J Psychiatry 159(7):1165–1173

    Article  PubMed  Google Scholar 

  • Habas C (2010) Functional connectivity of the human rostral and caudal cingulate motor areas in the brain resting state at 3T. Neuroradiology 52(1):47–59

    Article  PubMed  Google Scholar 

  • Hahn A, Stein P, Windischberger C, Weissenbacher A, Spindelegger C, Moser E, Kasper S, Lanzenberger R (2011) Reduced resting-state functional connectivity between amygdala and orbitofrontal cortex in social anxiety disorder. Neuroimage 56(3):881–889

    Article  PubMed  Google Scholar 

  • Hamani C, Mayberg H, Stone S, Laxton A, Haber S, Lozano AM (2011) The subcallosal cingulate gyrus in the context of major depression. Biol Psychiatry 69(4):301–308

    Article  PubMed  Google Scholar 

  • Hashimoto K, Kakiuchi T, Ohba H, Nishiyama S, Tsukada H (2016) Reduction of dopamine D2/3 receptor binding in the striatum after a single administration of esketamine, but not R-ketamine: a PET study in conscious monkeys. Eur Arch Psychiatry Clin Neurosci. doi:10.1007/s00406-016-0692-7

    PubMed Central  Google Scholar 

  • Hayton SM, Kriss A, Muller DP (1999) Comparison of the effects of four anaesthetic agents on somatosensory evoked potentials in the rat. Lab Anim 33(3):243–251

    Article  CAS  PubMed  Google Scholar 

  • Himmelseher S, Durieux ME (2005) Ketamine for perioperative pain management. Anesthesiology 102(1):211–220

    Article  PubMed  Google Scholar 

  • Hoflich A, Hahn A, Kublbock M, Kranz GS, Vanicek T, Windischberger C, Saria A, Kasper S, Winkler D, Lanzenberger R (2015) Ketamine-induced modulation of the thalamo-cortical network in healthy volunteers as a model for schizophrenia. Int J Neuropsychopharmacol 18(9). doi:10.1093/ijnp/pyv040

  • Jenkins BG (2012) Pharmacologic magnetic resonance imaging (phMRI): imaging drug action in the brain. Neuroimage 62(2):1072–1085

    Article  CAS  PubMed  Google Scholar 

  • Kegeles L, Mao X, Stanford AD et al (2012) Elevated prefrontal cortex γ-aminobutyric acid and glutamate-glutamine levels in schizophrenia measured in vivo with proton magnetic resonance spectroscopy. Arch Gen Psychiatry 69(5):449–459

    Article  CAS  PubMed  Google Scholar 

  • Kornhuber J, Mack-Burkhardt F, Riederer P, Hebenstreit GF, Reynolds GP, Andrews HB, Beckmann H (1989) [3H]MK-801 binding sites in postmortem brain regions of schizophrenic patients. J Neural Transm 77(2–3):231–236

    Article  CAS  PubMed  Google Scholar 

  • Krystal JH, Sanacora G, Duman RS (2013) Rapid-acting glutamatergic antidepressants: the path to ketamine and beyond. Biol Psychiatry 73(12):1133–1141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lehmann M, Seifritz E, Henning A, Walter M, Böker H, Scheidegger M, Grimm S (2016) Differential effects of rumination and distraction on ketamine induced modulation of resting state functional connectivity and reactivity of regions within the default-mode network. Soc Cogn Affect Neurosci 11(8):1227–1235

    Article  PubMed  Google Scholar 

  • Li N, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M, Li XY, Aghajanian G, Duman RS (2010) mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 329(5994):959–964

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li N, Liu RJ, Dwyer JM, Banasr M, Lee B, Son H, Li XY, Aghajanian G, Duman RS (2011) Glutamate N-methyl-d-aspartate receptor antagonists rapidly reverse behavioral and synaptic deficits caused by chronic stress exposure. Biol Psychiatry 69(8):754–761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lopez-Gil X, Babot Z, Amargos-Bosch M, Sunol C, Artigas F, Adell A (2007) Clozapine and haloperidol differently suppress the MK-801-increased glutamatergic and serotonergic transmission in the medial prefrontal cortex of the rat. Neuropsychopharmacology 32(10):2087–2097

    Article  CAS  PubMed  Google Scholar 

  • Lorrain DS, Baccei CS, Bristow LJ, Anderson JJ, Varney MA (2003) Effects of ketamine and N-methyl-d-aspartate on glutamate and dopamine release in the rat prefrontal cortex: modulation by a group II selective metabotropic glutamate receptor agonist LY379268. Neuroscience 117(3):697–706

    Article  CAS  PubMed  Google Scholar 

  • Margulies DS, Kelly AM, Uddin LQ, Biswal BB, Castellanos FX, Milham MP (2007) Mapping the functional connectivity of anterior cingulate cortex. Neuroimage 37(2):579–588

    Article  PubMed  Google Scholar 

  • Masamoto K, Kanno I (2012) Anesthesia and the quantitative evaluation of neurovascular coupling. J Cereb Blood Flow Metab 32(7):1233–1247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, Schwalb JM, Kennedy SH (2005) Deep brain stimulation for treatment-resistant depression. Neuron 45(5):651–660

    Article  CAS  PubMed  Google Scholar 

  • McCabe C, Mishor Z, Cowen PJ, Harmer CJ (2010) Diminished neural processing of aversive and rewarding stimuli during selective serotonin reuptake inhibitor treatment. Biol Psychiatry 67(5):439–445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murrough JW, Iosifescu DV, Chang LC, Al Jurdi RK, Green CE, Perez AM, Iqbal S, Pillemer S, Foulkes A, Shah A, Charney DS, Mathew SJ (2013a) Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry 170(10):1134–1142

    Article  PubMed  PubMed Central  Google Scholar 

  • Murrough JW, Perez AM, Pillemer S, Stern J, Parides MK, aan het Rot M, Collins KA, Mathew SJ, Charney DS, Iosifescu DV (2013b) Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression. Biol Psychiatry 74(4):250–256

    Article  CAS  PubMed  Google Scholar 

  • Musso F, Brinkmeyer J, Ecker D, London MK, Thieme G, Warbrick T, Wittsack HJ, Saleh A, Greb W, de Boer P, Winterer G (2011) Ketamine effects on brain function–simultaneous fMRI/EEG during a visual oddball task. Neuroimage 58(2):508–525

    Article  CAS  PubMed  Google Scholar 

  • Nobler MS, Oquendo MA, Kegeles LS, Malone KM, Campbell CC, Sackeim HA, Mann JJ (2001) Decreased regional brain metabolism after ECT. Am J Psychiatry 158(2):305–308

    Article  CAS  PubMed  Google Scholar 

  • Ossewaarde L, Verkes RJ, Hermans EJ, Kooijman SC, Urner M, Tendolkar I, van Wingen GA, Fernandez G (2011) Two-week administration of the combined serotonin-noradrenaline reuptake inhibitor duloxetine augments functioning of mesolimbic incentive processing circuits. Biol Psychiatry 70(6):568–574

    Article  CAS  PubMed  Google Scholar 

  • Palaniyappan L, Liddle PF (2012) Does the salience network play a cardinal role in psychosis? An emerging hypothesis of insular dysfunction. J Psychiatry Neurosci 37(1):17–27

    Article  PubMed  PubMed Central  Google Scholar 

  • Palomero-Gallagher N, Vogt BA, Schleicher A, Mayberg HS, Zilles K (2009) Receptor architecture of human cingulate cortex: evaluation of the four-region neurobiological model. Hum Brain Mapp 30(8):2336–2355

    Article  PubMed  Google Scholar 

  • Parsey RV, Ojha A, Ogden RT, Erlandsson K, Kumar D, Landgrebe M, Van Heertum R, Mann JJ (2006) Metabolite considerations in the in vivo quantification of serotonin transporters using 11C-DASB and PET in humans. J Nucl Med 47(11):1796–1802

    CAS  PubMed  Google Scholar 

  • Pham TH, Mendez-David I, Defaix C, Guiard BP, Tritschler L, David DJ, Gardier AM (2016) Ketamine treatment involves medial prefrontal cortex serotonin to induce a rapid antidepressant-like activity in BALB/cJ mice. Neuropharmacology. doi:10.1016/j.neuropharm.2016.05.010

  • Poels EM, Kegeles LS, Kantrowitz JT, Slifstein M, Javitt DC, Lieberman JA, Abi-Dargham A, Girgis RR (2014) Imaging glutamate in schizophrenia: review of findings and implications for drug discovery. Mol Psychiatry 19(1):20–29

    Article  CAS  PubMed  Google Scholar 

  • Rowland LM, Bustillo JR, Mullins PG, Jung RE, Lenroot R, Landgraf E, Barrow R, Yeo R, Lauriello J, Brooks WM (2005) Effects of ketamine on anterior cingulate glutamate metabolism in healthy humans: a 4-T proton MRS study. Am J Psychiatry 162(2):394–396

    Article  PubMed  Google Scholar 

  • Scheidegger M, Walter M, Lehmann M, Metzger C, Grimm S, Boeker H, Boesiger P, Henning A, Seifritz E (2012) Ketamine decreases resting state functional network connectivity in healthy subjects: implications for antidepressant drug action. PLoS One 7(9):e44799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scheidegger M, Henning A, Walter M, Lehmann M, Kraehenmann R, Boeker H, Seifritz E, Grimm S (2016) Ketamine administration reduces amygdalo-hippocampal reactivity to emotional stimulation. Hum Brain Mapp 37(5):1941–1952

    Article  PubMed  Google Scholar 

  • Shcherbinin S, Doyle O, Zelaya FO, de Simoni S, Mehta MA, Schwarz AJ (2015) Modulatory effects of ketamine, risperidone and lamotrigine on resting brain perfusion in healthy human subjects. Psychopharmacology 232(21–22):4191–4204

    Article  CAS  PubMed  Google Scholar 

  • Stone JM, Dietrich C, Edden R, Mehta MA, De Simoni S, Reed LJ, Krystal JH, Nutt D, Barker GJ (2012) Ketamine effects on brain GABA and glutamate levels with 1H-MRS: relationship to ketamine-induced psychopathology. Mol Psychiatry 17(7):664–665

    Article  CAS  PubMed  Google Scholar 

  • Taylor KS, Seminowicz DA, Davis KD (2009) Two systems of resting state connectivity between the insula and cingulate cortex. Hum Brain Mapp 30(9):2731–2745

    Article  PubMed  Google Scholar 

  • Taylor MJ, Tiangga ER, Mhuircheartaigh RN, Cowen PJ (2012) Lack of effect of ketamine on cortical glutamate and glutamine in healthy volunteers: a proton magnetic resonance spectroscopy study. J Psychopharmacol 26(5):733–737

    Article  PubMed  PubMed Central  Google Scholar 

  • Theberge J, Bartha R, Drost DJ, Menon RS, Malla A, Takhar J, Neufeld RW, Rogers J, Pavlosky W, Schaefer B, Densmore M, Al-Semaan Y, Williamson PC (2002) Glutamate and glutamine measured with 4.0 T proton MRS in never-treated patients with schizophrenia and healthy volunteers. Am J Psychiatry 159(11):1944–1946

    Article  PubMed  Google Scholar 

  • Vollenweider FX, Vontobel P, Øye I, Hell D, Leenders KL (2000) Effects of (S)-ketamine on striatal dopamine: a [11C]raclopride PET study of a model psychosis in humans. J Psychiatr Res 34(1):35–43

    Article  CAS  PubMed  Google Scholar 

  • Walter M, Li S, Demenescu LR (2014) Multistage drug effects of ketamine in the treatment of major depression. Eur Arch Psychiatry Clin Neurosci 264(Suppl 1):S55–S65

    Article  PubMed  Google Scholar 

  • Weissenbacher A, Kasess C, Gerstl F, Lanzenberger R, Moser E, Windischberger C (2009) Correlations and anticorrelations in resting-state functional connectivity MRI: a quantitative comparison of preprocessing strategies. Neuroimage 47(4):1408–1416

    Article  PubMed  Google Scholar 

  • Wise RG, Rogers R, Painter D, Bantick S, Ploghaus A, Williams P, Rapeport G, Tracey I (2002) Combining fMRI with a pharmacokinetic model to determine which brain areas activated by painful stimulation are specifically modulated by remifentanil. Neuroimage 16(4):999–1014

    Article  PubMed  Google Scholar 

  • Witkin JM, Monn JA, Schoepp DD, Li X, Overshiner C, Mitchell SN, Carter G, Johnson B, Rasmussen K, Rorick-Kehn LM (2016) The rapidly acting antidepressant ketamine and the mGlu2/3 receptor antagonist LY341495 rapidly engage dopaminergic mood circuits. J Pharmacol Exp Ther 358(1):71–82

    Article  CAS  PubMed  Google Scholar 

  • Yu C, Zhou Y, Liu Y, Jiang T, Dong H, Zhang Y, Walter M (2011) Functional segregation of the human cingulate cortex is confirmed by functional connectivity based neuroanatomical parcellation. Neuroimage 54(4):2571–2581

    Article  PubMed  Google Scholar 

  • Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK (2006) A randomized trial of an N-methyl-d-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 63(8):856–864

    Article  CAS  PubMed  Google Scholar 

  • Zhang WN, Chang SH, Guo LY, Zhang KL, Wang J (2013) The neural correlates of reward-related processing in major depressive disorder: a meta-analysis of functional magnetic resonance imaging studies. J Affect Disord 151(2):531–539

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

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.

Author information

Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria

    Anna Höflich, Andreas Hahn, Georg S. Kranz, Thomas Vanicek, Sebastian Ganger, Marie Spies, Siegfried Kasper, Dietmar Winkler & Rupert Lanzenberger

  2. MR Center of Excellence, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria

    Martin Küblböck & Christian Windischberger

Authors
  1. Anna Höflich
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andreas Hahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Martin Küblböck
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Georg S. Kranz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thomas Vanicek
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sebastian Ganger
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Marie Spies
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Christian Windischberger
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Siegfried Kasper
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Dietmar Winkler
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Rupert Lanzenberger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rupert Lanzenberger.

Ethics declarations

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.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Höflich, A., Hahn, A., Küblböck, M. et al. Ketamine-dependent neuronal activation in healthy volunteers. Brain Struct Funct 222, 1533–1542 (2017). https://doi.org/10.1007/s00429-016-1291-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00429-016-1291-0

Keywords

Search

Navigation