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Table of Contents
Vol. 64, No. 2, 2011
Issue release date: June 2011
Section title: Original Paper
Editor's Choice -- Free Access
Neuropsychobiology 2011;64:93–101

Brain Activity Supporting Working Memory Accuracy in Patients with Paranoid Schizophrenia: A Functional Magnetic Resonance Imaging Study

Wolf C.a · Linden S.a, b · Jackson M.C.a · Healy D.b · Baird A.c · Linden D.E.J.a, b · Thome J.c, d
aWolfson Centre for Cognitive and Clinical Neuroscience, School of Psychology, Bangor University, Bangor, and bDepartment of Psychological Medicine and Neurology, Cardiff University, Cardiff, and cLaboratory of Molecular Psychiatry and Pharmacology, Institute of Life Science, School of Medicine, Swansea University, Swansea, UK; dDepartment of Psychiatry and Psychotherapy, Rostock University, Rostock, Germany
email Corresponding Author

Prof. David Linden

MRC Centre for Neuropsychiatric Genetics and Genomics

Sir Henry Wellcome Building, Cardiff University School of Medicine

Cardiff CF14 4XN (UK)

Tel. +44 2920 687 928, E-Mail linden@cardiff.ac.uk


  1. Lee J, Park S: Working memory impairments in schizophrenia: a meta-analysis. J Abnorm Psychol 2005;114:599–611.
  2. Forbes NF, Carrick LA, McIntosh AM, Lawrie SM: Working memory in schizophrenia: a meta-analysis. Psychol Med 2009;29:889–905.
    External Resources
  3. Chen Y, Norton D, McBain R, Ongur D, Heckers S: Visual and cognitive processing of face information in schizophrenia: detection, discrimination and working memory. Schizophr Res 2009;107:92–98.
  4. Gooding DC, Tallent KA: Nonverbal working memory deficits in schizophrenia patients: evidence of a supramodal executive processing deficit. Schizophr Res 2004;68:189–201.
  5. Manoach DS: Prefrontal cortex dysfunction during working memory performance in schizophrenia: reconciling discrepant findings. Schizophr Res 2003;60:285–298.
  6. Honey GD, Fletcher PC: Investigating principles of human brain function underlying working memory: what insights from schizophrenia? Neuroscience 2006;139:59–71.
  7. Barch DM: The cognitive neuroscience of schizophrenia. Annu Rev Clin Psychol 2005;1:321–353.
  8. Linden D: The working memory networks of the human brain. Neuroscientist 2007;13:257–267.
  9. Perlstein W, Carter C, Noll D, Cohen J: Relation of prefrontal cortex dysfunction to working memory and symptoms in schizophrenia. Am J Psychiatry 2001;158:1105–1113.
  10. Thermenos HW, Goldstein JM, Buka SL, Poldrack RA, Koch JK, Tsuang MT, Seidman LJ: The effect of working memory performance on functional MRI in schizophrenia. Schizophr Res 2005;74:179–194.
  11. Kay SR, Fiszbein A, Opler LA: The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987;13:261–276.
  12. Wolf C, Jackson MC, Kissling C, Thome J, Linden DE: Dysbindin-1 genotype effects on emotional working memory. Mol Psychiatry 2011;16:145–155.
  13. Ekman P, Friesen WV: Pictures of Facial Affect. Palo Alto, Consulting Psychologists Press, 1976.
  14. Jackson M, Wolf C, Johnston S, Raymond J, Linden D: Neural correlates of enhanced visual short-term memory for angry faces: an FMRI study. PLoS One 2008;3:e3536.
  15. Schneider W, Eschman A, Zuccolotto A: E-Prime User’s Guide. Pittsburgh: Psychology Software Tools Inc., 2002.
  16. Cowan N: The magical number 4 in short-term memory: a reconsideration of mental storage capacity. Behav Brain Sci 2001;24:87–114; discussion 114–185.
  17. Talairach J, Tournoux P: Co-Planar Stereotaxic Atlas of the Human Brain. New York, Thieme, 1988.
  18. Gray JR, Braver TS, Raichle ME: Integration of emotion and cognition in the lateral prefrontal cortex. Proc Natl Acad Sci USA 2002;99:4115–4120.
  19. Rama P, Sala JB, Gillen JS, Pekar JJ, Courtney SM: Dissociation of the neural systems for working memory maintenance of verbal and nonspatial visual information. Cogn Affect Behav Neurosci 2001;1:161–171.
  20. Rama P, Poremba A, Sala JB, Yee L, Malloy M, Mishkin M, Courtney SM: Dissociable functional cortical topographies for working memory maintenance of voice identity and location. Cereb Cortex 2004;14:768–780.
  21. Mayer J, Bittner R, Nikolić D, Bledowski C, Goebel R, Linden D: Common neural substrates for visual working memory and attention. Neuroimage 2007;36:441–453.
  22. Pomarol-Clotet E, Salvador R, Sarro S, Gomar J, Vila F, Martinez A, Guerrero A, Ortiz-Gil J, Sans-Sansa B, Capdevila A, Cebamanos JM, McKenna PJ: Failure to deactivate in the prefrontal cortex in schizophrenia: dysfunction of the default mode network? Psychol Med 2008;38:1185–1193.
  23. Quintana J, Wong T, Ortiz-Portillo E, Kovalik E, Davidson T, Marder SR, Mazziotta JC: Prefrontal-posterior parietal networks in schizophrenia: primary dysfunctions and secondary compensations. Biol Psychiatry 2003;53:12–24.
  24. Manoach DS, Gollub RL, Benson ES, Searl MM, Goff DC, Halpern E, Saper CB, Rauch SL: Schizophrenic subjects show aberrant fMRI activation of dorsolateral prefrontal cortex and basal ganglia during working memory performance. Biol Psychiatry 2000;48:99–109.
  25. Karlsgodt KH, Sanz J, van Erp TG, Bearden CE, Nuechterlein KH, Cannon TD: Re-evaluating dorsolateral prefrontal cortex activation during working memory in schizophrenia. Schizophr Res 2009;108:143–150.
  26. Wolf RC, Vasic N, Hose A, Spitzer M, Walter H: Changes over time in frontotemporal activation during a working memory task in patients with schizophrenia. Schizophr Res 2007;91:141–150.
  27. Walter H, Wunderlich AP, Blankenhorn M, Schafer S, Tomczak R, Spitzer M, Gron G: No hypofrontality, but absence of prefrontal lateralization comparing verbal and spatial working memory in schizophrenia. Schizophr Res 2003;61:175–184.
  28. Johnson MR, Morris NA, Astur RS, Calhoun VD, Mathalon DH, Kiehl KA, Pearlson GD: A functional magnetic resonance imaging study of working memory abnormalities in schizophrenia. Biol Psychiatry 2006;60:11–21.
  29. Honey GD, Bullmore ET, Sharma T: De-coupling of cognitive performance and cerebral functional response during working memory in schizophrenia. Schizophr Res 2002;53:45–56.
  30. Perlstein WM, Dixit NK, Carter CS, Noll DC, Cohen JD: Prefrontal cortex dysfunction mediates deficits in working memory and prepotent responding in schizophrenia. Biol Psychiatry 2003;53:25–38.
  31. Brahmbhatt SB, Haut K, Csernansky JG, Barch DM: Neural correlates of verbal and nonverbal working memory deficits in individuals with schizophrenia and their high-risk siblings. Schizophr Res 2006;87:191–204.
  32. Gabrieli JD, Poldrack RA, Desmond JE: The role of left prefrontal cortex in language and memory. Proc Natl Acad Sci USA 1998;95:906–913.
  33. Pessoa L, Gutierrez E, Bandettini P, Ungerleider L: Neural correlates of visual working memory: fMRI amplitude predicts task performance. Neuron 2002;35:975–987.
  34. Fuster JM: The prefrontal cortex – an update: time is of the essence. Neuron 2001;30:319–333.
  35. Curtis CE, D’Esposito M: Persistent activity in the prefrontal cortex during working memory. Trends Cogn Sci 2003;7:415–423.
  36. Sack A, van de Ven V, Etschenberg S, Schatz D, Linden D: Enhanced vividness of mental imagery as a trait marker of schizophrenia? Schizophr Bull 2005;31:97–104.
  37. Prvulovic D, Hubl D, Sack AT, Melillo L, Maurer K, Frölich L, Lanfermann H, Zanella FE, Goebel R, Linden DE, Dierks T: Functional imaging of visuospatial processing in Alzheimer’s disease. Neuroimage 2002;17:1403–1414.
  38. Weinberger E, Cermak L: Short-term retention in acute and chronic paranoid schizophrenics. J Abnorm Psychol 1973;82:220–225.
  39. Fleming K, Goldberg TE, Gold JM, Weinberger DR: Verbal working memory dysfunction in schizophrenia: use of a Brown-Peterson paradigm. Psychiatry Res 1995;56:155–161.
  40. Spindler KA, Sullivan EV, Menon V, Lim KO, Pfefferbaum A: Deficits in multiple systems of working memory in schizophrenia. Schizophr Res 1997;27:1–10.
  41. Walter H, Vasic N, Hose A, Spitzer M, Wolf RC: Working memory dysfunction in schizophrenia compared to healthy controls and patients with depression: evidence from event-related fMRI. Neuroimage 2007;35:1551–1561.
  42. Haenschel C, Bittner R, Haertling F, Rotarska-Jagiela A, Maurer K, Singer W, Linden D: Contribution of impaired early-stage visual processing to working memory dysfunction in adolescents with schizophrenia: a study with event-related potentials and functional magnetic resonance imaging. Arch Gen Psychiatry 2007;64:1229–1240.
  43. Schlosser RG, Koch K, Wagner G, Nenadic I, Roebel M, Schachtzabel C, Axer M, Schultz C, Reichenbach JR, Sauer H: Inefficient executive cognitive control in schizophrenia is preceded by altered functional activation during information encoding: an fMRI study. Neuropsychologia 2008;46:336–347.
  44. Callicott JH, Mattay VS, Verchinski BA, Marenco S, Egan MF, Weinberger DR: Complexity of prefrontal cortical dysfunction in schizophrenia: more than up or down. Am J Psychiatry 2003;160:2209–2215.
  45. Meisenzahl EM, Scheuerecker J, Zipse M, Ufer S, Wiesmann M, Frodl T, Koutsouleris N, Zetzsche T, Schmitt G, Riedel M, Spellmann I, Dehning S, Linn J, Bruckmann H, Moller HJ: Effects of treatment with the atypical neuroleptic quetiapine on working memory function: a functional MRI follow-up investigation. Eur Arch Psychiatry Clin Neurosci 2006;256:522–531.
  46. Menzies L, Ooi C, Kamath S, Suckling J, McKenna P, Fletcher P, Bullmore E, Stephenson C: Effects of gamma-aminobutyric acid-modulating drugs on working memory and brain function in patients with schizophrenia. Arch Gen Psychiatry 2007;64:156–167.
  47. Goldberg TE, Goldman RS, Burdick KE, Malhotra AK, Lencz T, Patel RC, Woerner MG, Schooler NR, Kane JM, Robinson DG: Cognitive improvement after treatment with second-generation antipsychotic medications in first-episode schizophrenia: is it a practice effect? Arch Gen Psychiatry 2007;64:1115–1122.
  48. Keefe RS, Bilder RM, Davis SM, Harvey PD, Palmer BW, Gold JM, Meltzer HY, Green MF, Capuano G, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Davis CE, Hsiao JK, Lieberman JA: Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial. Arch Gen Psychiatry 2007;64:633–647.
  49. McGurk SR, Twamley EW, Sitzer DI, McHugo GJ, Mueser KT: A meta-analysis of cognitive remediation in schizophrenia. Am J Psychiatry 2007;164:1791–1802.