Advertisement

Psychopharmacology

, Volume 235, Issue 12, pp 3559–3571 | Cite as

Effects of ketamine on brain function during response inhibition

  • M. Steffens
  • C. Neumann
  • A.-M. Kasparbauer
  • B. Becker
  • B. Weber
  • M. A. Mehta
  • R. Hurlemann
  • U. Ettinger
Original Investigation

Abstract

Introduction

The uncompetitive N-methyl-D-aspartate (NMDA) receptor (NMDAR) antagonist ketamine has been proposed to model symptoms of psychosis. Inhibitory deficits in the schizophrenia spectrum have been reliably reported using the antisaccade task. Interestingly, although similar antisaccade deficits have been reported following ketamine in non-human primates, ketamine-induced deficits have not been observed in healthy human volunteers.

Methods

To investigate the effects of ketamine on brain function during an antisaccade task, we conducted a double-blind, placebo-controlled, within-subjects study on n = 15 healthy males. We measured the blood oxygen level dependent (BOLD) response and eye movements during a mixed antisaccade/prosaccade task while participants received a subanesthetic dose of intravenous ketamine (target plasma level 100 ng/ml) on one occasion and placebo on the other occasion.

Results

While ketamine significantly increased self-ratings of psychosis-like experiences, it did not induce antisaccade or prosaccade performance deficits. At the level of BOLD, we observed an interaction between treatment and task condition in somatosensory cortex, suggesting recruitment of additional neural resources in the antisaccade condition under NMDAR blockage.

Discussion

Given the robust evidence of antisaccade deficits in schizophrenia spectrum populations, the current findings suggest that ketamine may not mimic all features of psychosis at the dose used in this study. Our findings underline the importance of a more detailed research to further understand and define effects of NMDAR hypofunction on human brain function and behavior, with a view to applying ketamine administration as a model system of psychosis. Future studies with varying doses will be of importance in this context.

Keywords

Inhibitory control Antisaccades Ketamine Schizophrenia Psychosis Eye movements Experimental model system 

Notes

Acknowledgements

The authors thank Sam Hutton, Marcel Bartling, and Peter Trautner for their excellent technical support. The authors would like to thank Helen Röhrig and Inken Salhofen for their assistance in data collection and all volunteers who participated in the study.

Funding

The study was funded by the German Research Foundation (Deutsche Forschungsgemeinschaft; Et 31/2-1). The funding body had no role in the design of the study, data analysis, data interpretation, or publication.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

References

  1. Aichert DS, Wöstmann NM, Costa A, Macare C, Wenig JR, Möller H, Rubia K, Ettinger U (2012) Associations between trait impulsivity and prepotent response inhibition. J Clin Exp Neuropsychol 34:1016–1032.  https://doi.org/10.1080/13803395.2012.706261 CrossRefPubMedGoogle Scholar
  2. Anis NA, Berry SC, Burton NR, Lodge D (1983) The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate. Br J Pharmacol 79:565–575CrossRefGoogle Scholar
  3. Balslev D, Albert NB, Miall C (2011) Eye muscle proprioception is represented bilaterally in the sensorimotor cortex. Hum Brain Mapp 32:624–631.  https://doi.org/10.1002/hbm.21050 CrossRefPubMedPubMedCentralGoogle Scholar
  4. Balslev D, Odoj B, Karnath H-O (2013) Role of somatosensory cortex in visuospatial attention. J Neurosci 33:18311–18318.  https://doi.org/10.1523/JNEUROSCI.1112-13.2013 CrossRefPubMedGoogle Scholar
  5. Becker B, Androsch L, Jahn RT, Alich T, Striepens N, Markett S, Maier W, Hurlemann R (2013) Inferior frontal gyrus preserves working memory and emotional learning under conditions of impaired noradrenergic signaling. Front Behav Neurosci 7(197):1–12.  https://doi.org/10.3389/fnbeh.2013.00197 CrossRefGoogle Scholar
  6. Becker B, Steffens M, Zhao Z, Kendrick KM, Neumann C, Weber B, Schultz J, Mehta MA, Ettinger U, Hurlemann R (2017) General and emotion-specific neural effects of ketamine during emotional memory formation. Neuroimage 150.  https://doi.org/10.1016/j.neuroimage.2017.02.049 CrossRefGoogle Scholar
  7. Binkofski F, Fink GR, Geyer S, Buccino G, Gruber O, Shah NJ, Taylor JG, Seitz RJ, Zilles K, Freund H-J (2002) Neural activity in human primary motor cortex areas 4a and 4p is modulated differentially by attention to action. J Neurophysiol 88:514–519.  https://doi.org/10.1152/jn.00947.2001 CrossRefPubMedGoogle Scholar
  8. Brickenkamp R (2002) Test d2 Aufmerksamkeits-Belastungs-TestGoogle Scholar
  9. Calkins ME, Iacono WG, Curtis CE (2003) Smooth pursuit and antisaccade performance evidence trait stability in schizophrenia patients and their relatives. Int J Psychophysiol 49:139–146CrossRefGoogle Scholar
  10. Calkins ME, Iacono WG, Ones DS (2008) Eye movement dysfunction in first-degree relatives of patients with schizophrenia: a meta-analytic evaluation of candidate endophenotypes. Brain Cogn 68:436–461.  https://doi.org/10.1016/j.bandc.2008.09.001 CrossRefPubMedPubMedCentralGoogle Scholar
  11. Camchong J, Dyckman KA, Austin BP, Clementz BA, McDowell JE (2008) Common neural circuitry supporting volitional saccades and its disruption in schizophrenia patients and relatives. Biol Psychiatry 64:1042–1050.  https://doi.org/10.1016/j.biopsych.2008.06.015.Common CrossRefPubMedPubMedCentralGoogle Scholar
  12. Carhart-Harris RL, Brugger S, Nutt DJ, Stone JM (2013) Psychiatry’s next top model: cause for a re-think on drug models of psychosis and other psychiatric disorders. J Psychopharmacol 27:771–778.  https://doi.org/10.1177/0269881113494107 CrossRefPubMedGoogle Scholar
  13. Carpenter WT, Koenig JI (2008) The evolution of drug development in schizophrenia: past issues and future opportunities. Neuropsychopharmacology 33:2061–2079.  https://doi.org/10.1038/sj.npp.1301639 CrossRefPubMedGoogle Scholar
  14. Carter CS, Barch DM (2007) Cognitive neuroscience-based approaches to measuring and improving treatment effects on cognition in schizophrenia: the CNTRICS initiative. Schizophr Bull 33:1131–1137.  https://doi.org/10.1093/schbul/sbm081 CrossRefPubMedPubMedCentralGoogle Scholar
  15. Cohen J (1973) Eta-squared and partial eta-squared in fixed factor anova designs. Educ Psychol Meas 33:107–112.  https://doi.org/10.1177/001316447303300111 CrossRefGoogle Scholar
  16. Cohen J (1992) A power primer. Psychol Bull 112:155–159CrossRefGoogle Scholar
  17. Condy C, Wattiez N, Rivaud-Péchoux S, Gaymard B (2005) Ketamine-induced distractibility: an oculomotor study in monkeys. Biol Psychiatry 57:366–372.  https://doi.org/10.1016/j.biopsych.2004.10.036 CrossRefPubMedGoogle Scholar
  18. Corlett PR, Honey GD, Fletcher PC (2007) From prediction error to psychosis: ketamine as a pharmacological model of delusions. J Psychopharmacol 21:238–252.  https://doi.org/10.1177/0269881107077716 CrossRefPubMedGoogle Scholar
  19. Domino EF, Zsigmond EK, Domino LE, Domino KE, Kothary SP, Domino SE (1982) Plasma levels of ketamine and two of its metabolites in surgical patients using a gas chromatographic mass fragmentographic assay. Anesth Analg 61:87–92CrossRefGoogle Scholar
  20. Doyle OM, De Simoni S, Schwarz AJ, Brittain C, O’Daly OG, Williams SCR, 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 345:151–160.  https://doi.org/10.1124/jpet.112.201665 CrossRefPubMedGoogle Scholar
  21. Driesen NR, McCarthy G, Bhagwagar Z, Bloch MH, Calhoun VD, D’Souza DC, Gueorguieva R, He G, Leung H-C, Ramani R, Anticevic A, Suckow RF, Morgan PT, Krystal JH (2013) The impact of NMDA receptor blockade on human working memory-related prefrontal function and connectivity. Neuropsychopharmacology 38:2613–2622.  https://doi.org/10.1038/npp.2013.170 CrossRefPubMedPubMedCentralGoogle Scholar
  22. Eickhoff SB, Stephan KE, Mohlberg H, Grefkes C, Fink GR, Amunts K, Zilles K (2005) A new SPM toolbox for combining probabilistic cytoarchitectonic maps and functional imaging data. Neuroimage 25:1325–1335.  https://doi.org/10.1016/j.neuroimage.2004.12.034 CrossRefPubMedGoogle Scholar
  23. Ettinger U, Kumari V (2003) Pharmacological studies of smooth pursuit and antisaccade eye movements in schizophrenia: current status and directions for future research. Curr Neuropharmacol 1:285–300.  https://doi.org/10.2174/1570159033477017 CrossRefGoogle Scholar
  24. Ettinger U, Kumari V, Crawford TJ, Flak V, Sharma T, Davis RE, Corr PJ (2005) Saccadic eye movements, schizotypy, and the role of neuroticism. Biol Psychol 68:61–78.  https://doi.org/10.1016/j.biopsycho.2004.03.014 CrossRefPubMedGoogle Scholar
  25. Fukumoto-Motoshita M, Matsuura M, Ohkubo T, Ohkubo H, Kanaka N, Matsushima E, Taira M, Kojima T, Matsuda T (2009) Hyperfrontality in patients with schizophrenia during saccade and antisaccade tasks: a study with fMRI. Psychiatry Clin Neurosci 63:209–217.  https://doi.org/10.1111/j.1440-1819.2009.01941.x CrossRefPubMedGoogle Scholar
  26. Gooding DC (1999) Antisaccade task performance in questionnaire-identified schizotypes. Schizophr Res 35:157–166.  https://doi.org/10.1016/S0920-9964(98)00120-0 CrossRefPubMedGoogle Scholar
  27. Gooding DC, Basso MA (2008) The tell-tale tasks: a review of saccadic research in psychiatric patient populations. Brain Cogn 68:371–390.  https://doi.org/10.1016/j.bandc.2008.08.024 CrossRefPubMedPubMedCentralGoogle Scholar
  28. Grady C (2012) The cognitive neuroscience of ageing. Nat Rev Neurosci 13:491–505.  https://doi.org/10.1038/nrn3256 CrossRefPubMedPubMedCentralGoogle Scholar
  29. Heekeren K, Daumann J, Neukirch A, Stock C, Kawohl W, Norra C, Waberski TD, Gouzoulis-Mayfrank E (2008) Mismatch negativity generation in the human 5HT2A agonist and NMDA antagonist model of psychosis. Psychopharmacology 199:77–88.  https://doi.org/10.1007/s00213-008-1129-4 CrossRefPubMedPubMedCentralGoogle Scholar
  30. Holahan A-LVA-LV, O’Driscoll GA (2005) Antisaccade and smooth pursuit performance in positive- and negative-symptom schizotypy. Schizophr Res 76:43–54.  https://doi.org/10.1016/j.schres.2004.10.005 CrossRefPubMedGoogle Scholar
  31. Hutton SB, Ettinger U (2006) The antisaccade task as a research tool in psychopathology: a critical review. Psychophysiology 43:302–313.  https://doi.org/10.1111/j.1469-8986.2006.00403.x CrossRefPubMedGoogle Scholar
  32. Javitt DC (2009) When doors of perception close: bottom-up models of disrupted cognition in schizophrenia. Annu Rev Clin Psychol 5:249–275.  https://doi.org/10.1146/annurev.clinpsy.032408.153502 CrossRefPubMedPubMedCentralGoogle Scholar
  33. Javitt DC (2010) Glutamatergic theories of schizophrenia. Isr J Psychiatry Relat Sci 47:4–16PubMedGoogle Scholar
  34. Javitt DC, Zukin SR, Heresco-Levy U, Umbricht D (2012) Has an angel shown the way? Etiological and therapeutic implications of the PCP/NMDA model of schizophrenia. Schizophr Bull 38:958–966.  https://doi.org/10.1093/schbul/sbs069 CrossRefPubMedPubMedCentralGoogle Scholar
  35. Jennings JR (1987) Editorial policy on analyses of variance with repeated measures. Psychophysiology 24:474–475.  https://doi.org/10.1111/j.1469-8986.1987.tb00320.x CrossRefGoogle Scholar
  36. Joules R, Doyle OM, Schwarz AJ, O’Daly OG, Brammer M, Williams SC, Mehta MA (2015) Ketamine induces a robust whole-brain connectivity pattern that can be differentially modulated by drugs of different mechanism and clinical profile. Psychopharmacology 232:4205–4218.  https://doi.org/10.1007/s00213-015-3951-9 CrossRefPubMedPubMedCentralGoogle Scholar
  37. Kantrowitz JT, Javitt DC (2010) Thinking glutamatergically: changing concepts of schizophrenia based upon changing neurochemical models. Clin Schizophr Relat Psychoses.  https://doi.org/10.3371/CSRP.4.3.6 CrossRefGoogle Scholar
  38. Kohrs R, Durieux ME (1998) Ketamine: teaching an old drug new tricks. Anesth Analg 87:1186–1193.  https://doi.org/10.1097/00000539-199811000-00039 CrossRefPubMedGoogle Scholar
  39. Koychev I, Barkus E, Ettinger U, Killcross S, Roiser JP, Wilkinson L, Deakin B (2011) Evaluation of state and trait biomarkers in healthy volunteers for the development of novel drug treatments in schizophrenia. J Psychopharmacol 25:1207–1225.  https://doi.org/10.1177/0269881111414450 CrossRefPubMedGoogle Scholar
  40. Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD, Heninger GR, Bowers MB, Charney DS (1994) Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry 51:199–214.  https://doi.org/10.1001/archpsyc.1994.03950030035004 CrossRefPubMedGoogle Scholar
  41. Krystal JH, D’Souza DC, Mathalon D, Perry E, Belger A, Hoffman R (2003) NMDA receptor antagonist effects, cortical glutamatergic function, and schizophrenia: toward a paradigm shift in medication development. Psychopharmacology 169:215–233.  https://doi.org/10.1007/s00213-003-1582-z CrossRefPubMedGoogle Scholar
  42. Lahti AC, Weiler MA, Michaelidis T, Parwani A, Tamminga CA, Tamara Michaelidis BA, Parwani A, Tamminga CA (2001) Effects of ketamine in normal and schizophrenic volunteers. Neuropsychopharmacology 25:455–467.  https://doi.org/10.1016/S0893-133X(01)00243-3 CrossRefPubMedGoogle Scholar
  43. Leigh RJ, Zee DS (2006) The neurology of eye movements. Oxford University Press, Inc., New YorkGoogle Scholar
  44. Leonard CJ, Robinson BM, Kaiser ST, Hahn B, McClenon C, Harvey AN, Luck SJ, Gold JM (2013) Testing sensory and cognitive explanations of the antisaccade deficit in schizophrenia. J Abnorm Psychol 122:1111–1120.  https://doi.org/10.1037/a0034956 CrossRefPubMedPubMedCentralGoogle Scholar
  45. Lesh TA, Niendam TA, Minzenberg MJ, Carter CS (2011) Cognitive control deficits in schizophrenia: mechanisms and meaning. Neuropsychopharmacology 36:316–338.  https://doi.org/10.1038/npp.2010.156 CrossRefPubMedGoogle Scholar
  46. Ma L, Skoblenick K, Seamans JK, Everling S (2015) Ketamine-induced changes in the signal and noise of rule representation in working memory by lateral prefrontal neurons. J Neurosci 35:11612–11622.  https://doi.org/10.1523/JNEUROSCI.1839-15.2015 CrossRefPubMedGoogle Scholar
  47. Malhotra AK, Pinals DA, Adler CM, Elman I, Clifton A, Pickar D, Breier A (1997) Ketamine-induced exacerbation of psychotic symptoms and cognitive impairment in neuroleptic-free schizophrenics. Neuropsychopharmacology 17:141–150.  https://doi.org/10.1016/S0893-133X(97)00036-5 CrossRefPubMedGoogle Scholar
  48. Mason OJ, Morgan CJM, Stefanovic A, Curran HV (2008) The psychotomimetic states inventory (PSI): measuring psychotic-type experiences from ketamine and cannabis. Schizophr Res 103:138–142.  https://doi.org/10.1016/j.schres.2008.02.020 CrossRefPubMedGoogle Scholar
  49. McDowell JE, Clementz BA (2001) Behavioral and brain imaging studies of saccadic performance in schizophrenia. Biol Psychol 57:5–22.  https://doi.org/10.1016/S0301-0511(01)00087-4 CrossRefPubMedGoogle Scholar
  50. McDowell JE, Brown GG, Paulus M, Martinez A, Stewart SE, Dubowitz DJ, Braff DL (2002) Neural correlates of refixation saccades and antisaccades in normal and schizophrenia subjects. Biol Psychiatry 51:216–223.  https://doi.org/10.1016/S0006-3223(01)01204-5 CrossRefPubMedGoogle Scholar
  51. McDowell JE, Dyckman KA, Austin BP, Clementz BA (2008) Neurophysiology and neuroanatomy of reflexive and volitional saccades: evidence from studies of humans. Brain Cogn 68:255–270.  https://doi.org/10.1016/j.bandc.2008.08.016 CrossRefPubMedPubMedCentralGoogle Scholar
  52. Meyhöfer I, Steffens M, Kasparbauer A, Grant P, Weber B, Ettinger U (2015) Neural mechanisms of smooth pursuit eye movements in schizotypy. Hum Brain Mapp 36:340–353.  https://doi.org/10.1002/hbm.22632 CrossRefPubMedGoogle Scholar
  53. Meyhöfer I, Steffens M, Faiola E, Kasparbauer AM, Kumari V, Ettinger U (2017) Combining two model systems of psychosis: the effects of schizotypy and sleep deprivation on oculomotor control and psychotomimetic states. Psychophysiology.  https://doi.org/10.1111/psyp.12917 CrossRefGoogle Scholar
  54. Moghaddam B, Adams B, Verma A, Daly D (1997) Activation of glutamatergic neurotransmission by ketamine: a novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex. J Neurosci 17:2921–2927CrossRefGoogle Scholar
  55. Morgan, C.J.A., Mofeez, A., Brandner, B., Bromley, L., Curran, H Valerie, 2004. Ketamine impairs response inhibition and is positively reinforcing in healthy volunteers: a dose-response study Psychopharmacology (Berl) 172, 298–308.  https://doi.org/10.1007/s00213-003-1656-y CrossRefGoogle Scholar
  56. Morgan CJA, Huddy V, Lipton M, Curran HV, Joyce EM (2009) Is persistent ketamine use a valid model of the cognitive and oculomotor deficits in schizophrenia? Biol Psychiatry 65:1099–1102.  https://doi.org/10.1016/j.biopsych.2008.10.045 CrossRefPubMedPubMedCentralGoogle Scholar
  57. Morris SE, Cuthbert BN (2012) Research domain criteria: cognitive systems, neural circuits, and dimensions of behavior. Dialogues Clin Neurosci 14:29–37PubMedPubMedCentralGoogle Scholar
  58. Muetzelfeldt L, Kamboj SK, Rees H, Taylor J, Morgan CJA, Curran HV (2008) Journey through the K-hole: phenomenological aspects of ketamine use. Drug Alcohol Depend 95:219–229.  https://doi.org/10.1016/j.drugalcdep.2008.01.024 CrossRefPubMedGoogle Scholar
  59. Murray RM, Paparelli A, Morrison PD, Marconi A, Di Forti M (2013) What can we learn about schizophrenia from studying the human model, drug-induced psychosis? Am J Med Genet B Neuropsychiatr Genet 162:661–670.  https://doi.org/10.1002/ajmg.b.32177 CrossRefGoogle Scholar
  60. Nelson B, Whitford TJ, Lavoie S, Sass LA (2014) What are the neurocognitive correlates of basic self-disturbance in schizophrenia?: integrating phenomenology and neurocognition. Part 2 (Aberrant salience). Schizophr Res 152:20–27.  https://doi.org/10.1016/j.schres.2013.06.033 CrossRefPubMedGoogle Scholar
  61. Niesters M, Khalili-Mahani N, Martini C, Aarts L, van Gerven J, van Buchem MA, Dahan A, Rombouts S (2012) Effect of subanesthetic ketamine on intrinsic functional brain connectivity: a placebo-controlled functional magnetic resonance imaging study in healthy male volunteers. Anesthesiology 117:868–877.  https://doi.org/10.1097/ALN.0b013e31826a0db3 CrossRefPubMedGoogle Scholar
  62. O’Driscoll GA, Callahan BL (2008) Smooth pursuit in schizophrenia: a meta-analytic review of research since 1993. Brain Cogn 68:359–370.  https://doi.org/10.1016/j.bandc.2008.08.023 CrossRefPubMedGoogle Scholar
  63. O’Driscoll GA, Lenzenweger MF, Holzman PS (1998) Antisaccades and smooth pursuit eye tracking and schizotypy. Arch Gen Psychiatry 55:837–843.  https://doi.org/10.1001/archpsyc.55.9.837 CrossRefPubMedGoogle Scholar
  64. Poels EMP, Kegeles LS, Kantrowitz JT, Slifstein M, Javitt DC, Lieberman J a, Abi-Dargham A, Girgis RR (2014) Imaging glutamate in schizophrenia: review of findings and implications for drug discovery. Mol Psychiatry 19:20–29.  https://doi.org/10.1038/mp.2013.136 CrossRefPubMedGoogle Scholar
  65. Pollak TA, De Simoni S, Barimani B, Zelaya FO, Stone JM, Mehta MA (2015) Phenomenologically distinct psychotomimetic effects of ketamine are associated with cerebral blood flow changes in functionally relevant cerebral foci: a continuous arterial spin labelling study. Psychopharmacology 232:4515–4524.  https://doi.org/10.1007/s00213-015-4078-8 CrossRefPubMedGoogle Scholar
  66. Pynn LK, DeSouza JFX (2013) The function of efference copy signals: implications for symptoms of schizophrenia. Vis Res 76:124–133.  https://doi.org/10.1016/j.visres.2012.10.019 CrossRefPubMedGoogle Scholar
  67. Radant AD, Bowdle TA, Cowley DS, Kharasch ED, Roy-Byrne PP (1998) Does ketamine-mediated N-methyl-D-aspartate receptor antagonism cause schizophrenia-like oculomotor abnormalities? Neuropsychopharmacology 19:434–444.  https://doi.org/10.1016/S0893-133X(98)00030-X CrossRefPubMedGoogle Scholar
  68. Raemaekers M, Jansma JM, Cahn W, Van der Geest JN, van der Linden JA, Kahn RS, Ramsey NF (2002) Neuronal substrate of the saccadic inhibition deficit in schizophrenia investigated with 3-dimensional event-related functional magnetic resonance imaging. Arch Gen Psychiatry 59:313–320.  https://doi.org/10.1001/archpsyc.59.4.313 CrossRefPubMedGoogle Scholar
  69. Reilly JL, Lencer R, Bishop JR, Keedy SK, Sweeney JA (2008) Pharmacological treatment effects on eye movement control. Brain Cogn 68:415–435.  https://doi.org/10.1016/j.bandc.2008.08.026.Pharmacological CrossRefPubMedPubMedCentralGoogle Scholar
  70. Schmechtig A, Lees J, Perkins A, Altavilla A, Craig KJ, Dawson GR, William Deakin JF, Dourish CT, Evans LH, Koychev I, Weaver K, Smallman R, Walters J, Wilkinson LS, Morris R, Williams SCR, Ettinger U (2013) The effects of ketamine and risperidone on eye movement control in healthy volunteers. Transl Psychiatry 3:e334.  https://doi.org/10.1038/tp.2013.109 CrossRefPubMedPubMedCentralGoogle Scholar
  71. Skoblenick K, Everling S (2012) NMDA antagonist ketamine reduces task selectivity in macaque dorsolateral prefrontal neurons and impairs performance of randomly interleaved prosaccades and antisaccades. J Neurosci 32:12018–12027.  https://doi.org/10.1523/JNEUROSCI.1510-12.2012 CrossRefPubMedGoogle Scholar
  72. Skoblenick K, Everling S (2014) N-methyl-d-aspartate receptor antagonist ketamine impairs action-monitoring activity in the prefrontal cortex. J Cogn Neurosci 26:577–592.  https://doi.org/10.1162/jocn_a_00519 CrossRefPubMedGoogle Scholar
  73. Steeds H, Carhart-Harris RL, Stone JM (2015) Drug models of schizophrenia. Ther Adv Psychopharmacol 5:43–58.  https://doi.org/10.1177/2045125314557797 CrossRefPubMedPubMedCentralGoogle Scholar
  74. Steffens M, Becker B, Neumann C, Kasparbauer AM, Meyhöfer I, Weber B, Mehta MA, Hurlemann R, Ettinger U (2016) Effects of ketamine on brain function during smooth pursuit eye movements. Hum Brain Mapp 37:4047–4060.  https://doi.org/10.1002/hbm.23294 CrossRefPubMedGoogle Scholar
  75. Stone JM (2011) Glutamatergic antipsychotic drugs: a new dawn in the treatment of schizophrenia? Ther Adv Psychopharmacol.  https://doi.org/10.1177/2045125311400779 CrossRefGoogle Scholar
  76. Stone JM, Erlandsson K, Arstad E, Squassante L, Teneggi V, Bressan RA, Krystal JH, Ell PJ, Pilowsky LS (2008) Relationship between ketamine-induced psychotic symptoms and NMDA receptor occupancy - a [123I]CNS-1261 SPET study. Psychopharmacology 197:401–408.  https://doi.org/10.1007/s00213-007-1047-x CrossRefPubMedGoogle Scholar
  77. Stone JM, Raffin M, Morrison P, McGuire PK (2010) Review: the biological basis of antipsychotic response in schizophrenia. J Psychopharmacol 24:953–964.  https://doi.org/10.1177/0269881109106959 CrossRefPubMedGoogle Scholar
  78. Stone JM, Dietrich C, Edden R, Mehta M a, 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 17:664–665.  https://doi.org/10.1038/mp.2011.171 CrossRefPubMedGoogle Scholar
  79. Stone J, Kotoula V, Dietrich C, De Simoni S, Krystal JH, Mehta MA (2015) Perceptual distortions and delusional thinking following ketamine administration are related to increased pharmacological MRI signal changes in the parietal lobe. J Psychopharmacol 29:1025–1028.  https://doi.org/10.1177/0269881115592337 CrossRefPubMedGoogle Scholar
  80. Umbricht D, Krljes S (2005) Mismatch negativity in schizophrenia: a meta-analysis. Schizophr Res 76:1–23.  https://doi.org/10.1016/j.schres.2004.12.002 CrossRefPubMedGoogle Scholar
  81. van Os J, Kapur S (2009) Schizophrenia. Lancet 374:635–645.  https://doi.org/10.1016/S0140-6736(09)60995-8 CrossRefPubMedGoogle Scholar
  82. Wood J, Kim Y, Moghaddam B (2012) Disruption of prefrontal cortex large scale neuronal activity by different classes of psychotomimetic drugs. J Neurosci 32:3022–3031.  https://doi.org/10.1523/JNEUROSCI.6377-11.2012 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • M. Steffens
    • 1
  • C. Neumann
    • 2
  • A.-M. Kasparbauer
    • 1
  • B. Becker
    • 3
    • 4
  • B. Weber
    • 5
    • 6
    • 7
  • M. A. Mehta
    • 8
  • R. Hurlemann
    • 3
  • U. Ettinger
    • 1
  1. 1.Department of PsychologyUniversity of BonnBonnGermany
  2. 2.Department of AnesthesiologyUniversity of BonnBonnGermany
  3. 3.Department of Psychiatry and Division of Medical PsychologyUniversity of BonnBonnGermany
  4. 4.Key Laboratory for NeuroInformation of Ministry of Education, Center for Information in BioMedicineUniversity of Electronic Science and Technology of ChinaChengduChina
  5. 5.Center for Economics and NeuroscienceUniversity of BonnBonnGermany
  6. 6.Department of EpileptologyUniversity Hospital BonnBonnGermany
  7. 7.Department of NeuroCognition/ImagingLife&Brain Research CenterBonnGermany
  8. 8.Department of NeuroimagingInstitute of Psychiatry Psychology and Neuroscience, King’s College LondonLondonUK

Personalised recommendations