Relationship between exploratory eye movements and brain morphology in schizophrenia spectrum patients

Voxel–based morphometry of three–dimensional magnetic resonance imaging
  • M. Tsunoda
  • Y. Kawasaki
  • M. Matsui
  • Y. Tonoya
  • H. Hagino
  • M. Suzuki
  • H. Seto
  • M. KurachiEmail author


The exploratory eye movements of schizophrenia patients and their relatives have been shown to differ from those of patients without schizophrenia and healthy controls. However the mechanism of exploratory eye movement disturbances in schizophrenia patients remains elusive. We investigated the relationship between the exploratory eye movements and brain morphology in 39 schizophrenia spectrum patients. Voxel–based morphometric analysis on three–dimensional magnetic resonance imaging was conducted by means of statistical parametric mapping 99. The decrease in the responsive search score, which is the total number of sections on which the eyes fixed in response to questioning in a comparison task, was significantly correlated with the decreased gray matter in the right frontal eye field (rFEF) including the right supplementary eye field (rSEF), right parietal eye field (rPEF), and right inferior frontal region. These results suggest that disturbance in exploratory eye movement in schizophrenia spectrum patients may be related to neural network dysfunction in FEF, SEF and PEF, which are the eye movement related areas, and in the inferior frontal region that may be related to information organization.

Key words

exploratory eye movement magnetic resonance imaging voxel–based morphometry inferior frontal gyrus schizophrenia spectrum disorder 


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  1. 1.
    Andersen RA, Gnadt JW (1989) Posterior parietal cortex. In: Wurtz H,Goldberg ME (eds) The neurobiology of saccadic eye movements. Elsevier, Amsterdam, pp 315–336Google Scholar
  2. 2.
    Ashburner J, Friston K (1997) Multimodal image coregistration and partitioning: a unified framework. Neuroimage 6:209–217CrossRefPubMedGoogle Scholar
  3. 3.
    Ashburner J, Friston KJ (2000) Voxel-based morphometry – The methods. Neuroimage 11:805–821CrossRefPubMedGoogle Scholar
  4. 4.
    Baron M, Risch N (1987) The spectrum concept of schizophrenia: evidence for a genetic-environmental continuum. J Psychiatric Res 21:257–267Google Scholar
  5. 5.
    Benes FM, NcSparren J, Bird ED, SanGiovanni JP, Vincent SL (1991) Deficits in small interneurons in prefrontal and cingulate cortices of schizophrenic and schizoaffective patients. Arch Gen Psychiatry 48:996–1001PubMedGoogle Scholar
  6. 6.
    Buchanan RW, Vladar K, Barta PE, Pearlson GD (1998) Structural evaluation of the prefrontal cortex in schizophrenia. Am J Psychiatry 155:1049–1055PubMedGoogle Scholar
  7. 7.
    Corbetta M, Akbudak E, Conturo TE, Snyder AZ, Ollinger JM, Drury HA, Linenweber MR, Petersen SE, Raichle ME, Van Essen DC, Shulman GL (1998) A common network of functional areas for attention and eye movements. Neuron 21:761–773CrossRefPubMedGoogle Scholar
  8. 8.
    Dickey CC, McCarley RW, Shenton ME (2002) The brain in schizotypal personality disorder: a review of structural MRI and CT findings. Harvard Rev Psychiatry 10:1–15Google Scholar
  9. 9.
    Diefendorf AR, Dogde R (1908) An experimental study of the ocular reactions of the insane from photographic records. Brain 31:451–489Google Scholar
  10. 10.
    First MB, Spitzer RL,Williams JBW, Gibson M (1996) Structured Clinical Interview for DSM-IV axis II disorders. New York State Psychiatric Institute, New YorkGoogle Scholar
  11. 11.
    Fletcher PC, Shallice T, Dolan RJ (1998) The functional roles of prefrontal cortex in episodic memory I. Encoding. Brain 121:1239–1248CrossRefPubMedGoogle Scholar
  12. 12.
    Friston KJ, Frith CD, Liddle PF, Dolan RJ, Lammertsma AA, Frackowiak, RSJ (1990) The relationship between global and local changes in PET scans. J Cereb Blood Flow Metab 10:458–466PubMedGoogle Scholar
  13. 13.
    Gaymard B, Ploner CJ, Rivaud S, Vermersch AI, Pierrot-Deseilligny C (1998) Cortical control of saccades. Exp Brain Res 123:159–163CrossRefPubMedGoogle Scholar
  14. 14.
    Goldberg ME, Segraves MA (1989) The visual and frontal cortices. In: Wurtz RH,Goldberg ME (eds) The neurobiology of saccadic eye movements. Elsevier, Amsterdam, pp 283–314Google Scholar
  15. 15.
    Hagino H, Suzuki M, Mori K, Nohara S, Yamashita I, Takahashi T, Kurokawa K, Matsui M, Watanabe N, Seto H, Kurachi M (2002) Proton magnetic resonance spectroscopy of the inferior frontal gyrus and thalamus and its relationship to verbal learning task performance in patients with schizophrenia: a preliminary report. Psychiatry Clin Neurosci 56:499–507Google Scholar
  16. 16.
    Heide W, Kompf D (1998) Combined deficits of saccades and visuo- spatial orientation after cortical lesions. Exp Brain Res 123:164–171CrossRefPubMedGoogle Scholar
  17. 17.
    Holzman PS, Proctor LR, Hughes DW (1973) Eye tracking patterns in schizophrenia. Science 181:179–181PubMedGoogle Scholar
  18. 18.
    Kendler KS, Masterson CC, Urgaro R, Davis KL (1984) A family history study of schizophrenia-related personality disorders. Am J Psychiatry 141:424–427PubMedGoogle Scholar
  19. 19.
    Kawasaki Y, Suzuki M, Nohara S, Hagino H, Takahashi T, Matsui M, Yamashita I, Chitnis XA, McGuire PK, Seto H, Kurachi M (2004) Structural brain differences in patients with schizophrenia and schizotypal disorder demonstrated by voxel-based morphometry. Eur Arch Psychiatry Clin Neurosci (in press)Google Scholar
  20. 20.
    Kendler KS, Neale MC, Walsh D (1995) Evaluating the spectrum concept of schizophrenia in the Roscommon family study. Am J Psychiatry 152:749–754PubMedGoogle Scholar
  21. 21.
    Kojima T, Matsushima E, Nakajima K, Shiraishi H, Ando K, Ando H, Shimazono Y (1990) Eye movements in acute, chronic and remitted schizophrenics. Biol Psychiatry 27:975–989CrossRefPubMedGoogle Scholar
  22. 22.
    Kojima T, Matsushima E, Ando K, Ando H (1992) Exploratory eye movements and neuropsychological tests in schizophrenic patients. Schizophr Bull 18:85–94PubMedGoogle Scholar
  23. 23.
    Kojima T, Matsushima E, Ando K (eds) (2000) Eyes and the mind. Japan Scientific Societies Press and S Karger, Tokyo BaselGoogle Scholar
  24. 24.
    Kojima T, Matsushima E, Ohta K, Toru M (2001) Stability of exploratory eye movements as a marker of schizophrenia – a WHO multi-center study. Schizophr Res 52:203–213CrossRefPubMedGoogle Scholar
  25. 25.
    Kurachi M, Matsui M, Kiba K, Suzuki M, Tsunoda M, Yamaguchi N, (1994) Limited visual search on the WAIS picture completion test in patients with schizophrenia. Schizophr Res 12:75–80CrossRefPubMedGoogle Scholar
  26. 26.
    Lawrie SM, Abukmeil SS (1998) Brain abnormality in schizophrenia: a systematic and quantitative review of volumetric magnetic resonance imaging studies. Br J Psychiatry 172:110–120PubMedGoogle Scholar
  27. 27.
    Lawrie SM, Whalley H, Kestelman JN, Abukmeil SS, Byrne M, Hodges A, Rimmington JE, Best JJ, Owens DG, Johnstone EC (1999) Magnetic resonance imaging of brain in people at high risk of developing schizophrenia. Lancet 353:30–33CrossRefPubMedGoogle Scholar
  28. 28.
    Lawrie SM, Whalley HC, Abukmeil SS, Kestelman JN, Donnelly L, Miller P, Best JJK, Owens BDGC, Johnstone EC (2001) Brain structure, genetic liability, and psychotic symptoms in subjects at high risk of developing schizophrenia. Biol Psychiatry 49:811–823CrossRefPubMedGoogle Scholar
  29. 29.
    Matsushima E, Kojima T, Ohbayashi S, Ando H, Ando K, Shimazono Y (1992) Exploratory eye movements in schizophrenic patients and patients with frontal lobe lesions. Eur Arch Psychiatry Clin Neurosci 241:310–314Google Scholar
  30. 30.
    Matsushima E, Takebayashi H, Kojima T (1996) Abnormalexploratory eye movements and cognitive mechanism in patients with schizophrenia. Rinsho Noha (Clinical Electroencephalography) 38:291–294 (in Japanese)Google Scholar
  31. 31.
    Matsushima E, Kojima T, Ohta K, Obayashi S, Nakajima K, Kakuma T, Ando H, Toru M (1998) Exploratory eye movement dysfunctions in patients with schizophrenia: possibility as a discriminator for schizophrenia. J Psychiatr Res 32:289–295CrossRefPubMedGoogle Scholar
  32. 32.
    Matsushima E, Kubo H, Kojima T, Ohta K (1999) Exploratory eye movement in patients with schizophrenia – a monozygotic twins study. In: Abstracts II of the XI World Congress of Psychiatry, Hamburg, p 11Google Scholar
  33. 33.
    Moriya H, Ando K,Kojima T, Shimazono Y, Ogiwara R, Jimbo K, Ushikubo T (1972) Eye movements during perception of pictures I chronic schizophrenia. Folia Psychiat Neurol Jpn 26:189–199PubMedGoogle Scholar
  34. 34.
    Nohara S, Suzuki M, Kurachi M, Yamashita I, Masui M, Seto H, Saitoh O (2000) Neural correlates of memory organization deficits schizophrenia – A single photon emission computed tomography study with 99m Tc-ECD during a verbal learning task. Schizophr Res 42:209–222CrossRefPubMedGoogle Scholar
  35. 35.
    Pierrot-Deseilligny C, Rivaud S, Gaymard B, Muri R, Vermersch AI (1995) Cortical control of saccades. Ann Neurol 37:557–567PubMedGoogle Scholar
  36. 36.
    Pierrot-Deseilligny C, Gaymard B, Muri R, Rivaud S (1997) Cerebral ocular motor sign. J Neurol 244:65–70CrossRefPubMedGoogle Scholar
  37. 37.
    Schlaepfer TE, Harris GJ, Tien AY, Peng LW, Lee S, Federman EB, Chase GA, Barta PE, Pearlson GD (1994) Decreased regional cortical gray matter volume in schizophrenia. Am J Psychiatry 151:842–848PubMedGoogle Scholar
  38. 38.
    Seidman LJ, Faraone SV, Goldstein JM, Kremen WS, Horton NJ, Makris N, Toomey R, Kennedy D, Caviness VS, Tsuang MT (2002) Left hippocampal volume as a vulnerability indicator for schizophrenia: a magnetic resonance imaging morphometric study of nonpsychotic first-degree relatives. Arch Gen Psychiatry 59:839–849CrossRefPubMedGoogle Scholar
  39. 39.
    Selemon LD, Rajkowska G, Goldman-Rakic PS (1995) Abnormally high neuronal density in the schizophrenic cortex. Arch Gen Psychiatry 52:805–818PubMedGoogle Scholar
  40. 40.
    Shagass C, Roemer RA, Amadeo M (1976) Eye-tracking performance and engagement of attention. Arch Gen Psychiatry 33:121–125PubMedGoogle Scholar
  41. 41.
    Shenton ME, Dickey CC, Frumin M, McCarley RW (2001) A review of MRI findings in schizophrenia. Schizophr Res 49:1–52Google Scholar
  42. 42.
    Siever LJ, Koeningsberg HW, Harvey P, Mitropoulou V, Laruelle M, Abi-Dargham A, Goodman M, Buchsbaum M (2002) Cognitive and brain function in schizotypal personality disorder. Schizophr Res 54:157–167CrossRefPubMedGoogle Scholar
  43. 43.
    Suzuki M, Nohara S, Hagino H, Kurokawa K, Yotsutsuji T, Kasasaki Y, Takahashi T, Matsui M, Watanabe N, Seto H, Kurachi M (2002) Regional changes in brain gray and white matter in patients with schizophrenia demonstrated with voxel-based analysis of MRI. Schizophr Res 55:41–54CrossRefPubMedGoogle Scholar
  44. 44.
    Takahashi S, Tanabe E, Sakai T, Xia M, Matsuura M, Matsushima E, Obayashi S, Kojima T (1996) Correlation between neurophysiological abnormalities and brain morphological changes in schizophrenia. Rinsho Noha (Clinical Electroencephalography) 38:85–91 (in Japanese)Google Scholar
  45. 45.
    Takahashi S, Tanabe E, Kojima T, Matsushima E, Yara K (1999) Exploratory eye movement of dysfunction in schizophrenic patients and their siblings. In: Abstracts II of the XI World Congress of Psychiatry, Hamburg, p 15Google Scholar
  46. 46.
    Takahashi T, Suzuki M, Kawasaki Y, Kurokawa K, Hagino H, Yamashita I, Zhou S-Y, Nohara S, Nakamura K, Seto H, Kurachi M (2002) Volumetric magnetic resonance imaging study of the anterior cingulate gyrus in schizotypal disorder. Eur Arch Psychiatry Clin Neurosci 252:268–277PubMedGoogle Scholar
  47. 47.
    Talairach J, Tournoux P (1998) Co-planar stereotaxic atlas of the human brain. Georg Thieme, Stuttgart-New YorkGoogle Scholar
  48. 48.
    Tonoya Y, Matsui M, Kurachi M, Kurokawa K, Sumiyoshi T (2002) Exploratory eye movements in schizophrenia: effects of figure size and the instruction on visual search. Eur Arch Psychiatry Clin Neurosci 252:255–261PubMedGoogle Scholar
  49. 49.
    Tsuang MT, Bucher KD, Fleming JA (1983) A search for ‘schizophrenia spectrum disorders’. An application of a multiple threshold model to blind family study data. Br J Psychiatry 143:572–577PubMedGoogle Scholar
  50. 50.
    Tsunoda M, Kurachi M, Yuasa S, Kadono Y, Matsui M, Shimizu A, (1992) Scanning eye movements in schizophrenic patients: relationship to clinical symptoms and regional cerebral blood flow using 123I-IMP SPECT. Schizophr Res 7:159–168CrossRefPubMedGoogle Scholar
  51. 51.
    Van Erp TG, Saleh PA, Rosso IM, Huttunen M, Lonnqvist J, Pirkola T, Salonen O, Valanne L, Poutanen VP, Standerskjold- Nordenstam CG, Cannon TD (2002) Contributions of genetic risk and fetal hypoxia to hippocampal volume in patients with schizophrenia or schizoaffective disorder, their unaffected siblings, and healthy unrelated volunteers. Am J Psychiatry 159:1514–1520Google Scholar
  52. 52.
    Wing JK, Cooper JE, Sartorius N (1974) Measurement and classification of psychiatric symptoms.An introduction manual for the PSE and CATEGO program. Cambridge University Press, LondonGoogle Scholar
  53. 53.
    World Health Organization (1993) The ICD-10 Classification of Mental and Behavioural Disorders: Diagnostic Criteria for Research. World Health Organization, GenevaGoogle Scholar
  54. 54.
    Wright IC, Ellison ZR, Sharma T, Friston KJ, Murray RM, McGuire PK (1999) Mapping of grey matter changes in schizophrenia. Schizophr Res 35:1–14Google Scholar
  55. 55.
    Wright IC, Rabe-Hesketh S, Woodruff PWR, David AS, Murray RM, Bullmore ET (2000) Meta-analysis of regional brain volumes in schizophrenia. Am J Psychiatry 157:16–25PubMedGoogle Scholar
  56. 56.
    Xia ML, Takahashi S, Tanabe E, Matsushima M, Kojima T, Matsushima E (1996) Eye movement studies on schizophrenics and their parents. Eur Neuropsychopharm 6(Suppl 3):64Google Scholar
  57. 57.
    Yoneyama E, Matsui M, Kawasaki Y, Nohara S, Takahashi T, Hagino H, Suzuki M, Seto H, Kurachi M (2003) Gray matter features of schizotypal disorder patients exhibiting the schizophrenia- related code types of the Minnesota Multiphasic Personality Inventory. Acta Psychiatr Scand 108:333–340CrossRefPubMedGoogle Scholar
  58. 58.
    Zipursky RB, Lim KO, Sullivan EV, Brown BW, Pfefferbaum A (1992) Widespread cerebral gray matter volume deficits in schizophrenia. Arch Gen Psychiatry 49:195–205PubMedGoogle Scholar

Copyright information

© Steinkopff Verlag 2004

Authors and Affiliations

  • M. Tsunoda
    • 1
  • Y. Kawasaki
    • 1
  • M. Matsui
    • 2
  • Y. Tonoya
    • 1
  • H. Hagino
    • 1
  • M. Suzuki
    • 1
  • H. Seto
    • 3
  • M. Kurachi
    • 1
    Email author
  1. 1.Department of NeuropsychiatryToyama Medical and Pharmaceutical UniversityToyama 930-0194Japan
  2. 2.Department of PsychologyToyama Medical and Pharmaceutical UniversityToyama 930-0194Japan
  3. 3.Department of RadiologyToyama Medical and Pharmaceutical UniversityToyama 930-0194Japan

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