Skip to main content
SpringerLink
Log in

Disrupted white matter integrity of corticopontine-cerebellar circuitry in schizophrenia

  • Original Paper
  • Published:
European Archives of Psychiatry and Clinical Neuroscience Aims and scope Submit manuscript

Abstract

Evidence for white matter abnormalities in patients with schizophrenia is increasing. Decreased fractional anisotropy (FA) in interhemispheric commissural fibers as well as long-ranging fronto-parietal association fibers belongs to the most frequent findings. The present study used tract-based spatial statistics to investigate white matter integrity in 35 patients with schizophrenia and 35 healthy volunteers. We found that patients exhibited significantly decreased FA relative to healthy subjects in the corpus callosum, the cerebral peduncle, the left inferior fronto-occipital fasciculus, the anterior thalamic radiation, the right posterior corona radiata, the middle cerebellar peduncle, and the right superior longitudinal fasciculus. Increased FA was detectable in the inferior sections of the corticopontine-cerebellar circuit. Present data indicate extended cortical-subcortical alterations of white matter integrity in schizophrenia using advanced data analysis strategies. They corroborate preceding findings of white matter structural deficits in mainly long-ranging association fibers and provide first evidence for neuroplastic changes in terms of an increased directionality in more inferior fiber tracts.

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
Fig. 3

Similar content being viewed by others

References

  1. Andreasen NC (1997) Linking mind and brain in the study of mental illnesses: a project for a scientific psychopathology. Science 275:1586–1593

    Article  CAS  PubMed  Google Scholar 

  2. Atkins M, Burgess A, Bottomley C, Riccio M (1997) Chlorpromazine equivalents: a consensus of opinion for both clinical and research applications. Psychiatr Bull 21:224–226

    Article  Google Scholar 

  3. Bai O, Chlan-Fourney J, Bowen R, Keegan D, Li XM (2003) Expression of brain-derived neurotrophic factor mRNA in rat hippocampus after treatment with antipsychotic drugs. J Neurosci Res 71:127–131

    Article  CAS  PubMed  Google Scholar 

  4. Brodal P (1978) The corticopontine projection in the rhesus monkey. Origin and principles of organization. Brain 101:251–283

    Article  CAS  PubMed  Google Scholar 

  5. Brodal P, Bjaalie JG (1992) Organization of the pontine nuclei. Neurosci Res 13:83–118

    Article  CAS  PubMed  Google Scholar 

  6. Burns J, Job D, Bastin ME, Whalley H, Macgillivray T, Johnstone EC, Lawrie SM (2003) Structural disconnectivity in schizophrenia: a diffusion tensor magnetic resonance imaging study. Br J Psychiatry 182:439–443

    Article  CAS  PubMed  Google Scholar 

  7. Cahn W, Rais M, Stigter FP, van Haren NE, Caspers E, Hulshoff Pol HE, Xu Z, Schnack HG, Kahn RS (2009) Psychosis and brain volume changes during the first five years of schizophrenia. Eur Neuropsychopharmacol 19:147–151

    Article  CAS  PubMed  Google Scholar 

  8. Cheung V, Cheung C, McAlonan GM, Deng Y, Wong JG, Yip L, Tai KS, Khong PL, Sham P, Chua SE (2008) A diffusion tensor imaging study of structural dysconnectivity in never-medicated, first-episode schizophrenia. Psychol Med 38:877–885

    Article  CAS  PubMed  Google Scholar 

  9. Dazzan P, Murray RM (2002) Neurological soft signs in first-episode psychosis: a systematic review. Br J Psychiatry Suppl 43:s50–s57

    Article  PubMed  Google Scholar 

  10. Douaud G, Smith S, Jenkinson M, Behrens T, Johansen-Berg H, Vickers J, James S, Voets N, Watkins K, Matthews PM, James A (2007) Anatomically related grey and white matter abnormalities in adolescent-onset schizophrenia. Brain 130:2375–2386

    Article  PubMed  Google Scholar 

  11. Foong J, Maier M, Clark CA, Barker GJ, Miller DH, Ron MA (2000) Neuropathological abnormalities of the corpus callosum in schizophrenia: a diffusion tensor imaging study. J Neurol Neurosurg Psychiatry 68:242–244

    Article  CAS  PubMed  Google Scholar 

  12. Forstmann BU, Jahfari S, Scholte HS, Wolfensteller U, van den Wildenberg WP, Ridderinkhof KR (2008) Function and structure of the right inferior frontal cortex predict individual differences in response inhibition: a model-based approach. J Neurosci 28:9790–9796

    Article  CAS  PubMed  Google Scholar 

  13. Foucher JR, Vidailhet P, Chanraud S, Gounot D, Grucker D, Pins D, Damsa C, Danion JM (2005) Functional integration in schizophrenia: too little or too much? Preliminary results on fMRI data. Neuroimage 26:374–388

    Article  CAS  PubMed  Google Scholar 

  14. Friedman JI, Tang C, Carpenter D, Buchsbaum M, Schmeidler J, Flanagan L, Golembo S, Kanellopoulou I, Ng J, Hof PR, Harvey PD, Tsopelas ND, Stewart D, Davis KL (2008) Diffusion tensor imaging findings in first-episode and chronic schizophrenia patients. Am J Psychiatry 165:1024–1032

    Article  PubMed  Google Scholar 

  15. Fujiwara H, Namiki C, Hirao K, Miyata J, Shimizu M, Fukuyama H, Sawamoto N, Hayashi T, Murai T (2007) Anterior and posterior cingulum abnormalities and their association with psychopathology in schizophrenia: a diffusion tensor imaging study. Schizophr Res 95:215–222

    Article  PubMed  Google Scholar 

  16. Gasparotti R, Valsecchi P, Carletti F, Galluzzo A, Liserre R, Cesana B, Sacchetti E (2009) Reduced fractional anisotropy of corpus callosum in first-contact, antipsychotic drug-naive patients with schizophrenia. Schizophr Res 108:41–48

    Article  PubMed  Google Scholar 

  17. Güllmar D, Haueisen J, Reichenbach JR (2005) Analysis of the b-value calculations in diffusion weighted and diffusion tensor imaging. Concepts Magn Reson 25A:53–66

    Article  Google Scholar 

  18. Habas C, Cabanis EA (2007) Anatomical parcellation of the brainstem and cerebellar white matter: a preliminary probabilistic tractography study at 3 T. Neuroradiology 49:849–863

    Article  PubMed  Google Scholar 

  19. Hao Y, Liu Z, Jiang T, Gong G, Liu H, Tan L, Kuang F, Xu L, Yi Y, Zhang Z (2006) White matter integrity of the whole brain is disrupted in first-episode schizophrenia. Neuroreport 17:23–26

    Article  PubMed  Google Scholar 

  20. Honey GD, Fletcher PC (2006) Investigating principles of human brain function underlying working memory: what insights from schizophrenia? Neuroscience 139:59–71

    Article  CAS  PubMed  Google Scholar 

  21. Hubl D, Koenig T, Strik W, Federspiel A, Kreis R, Boesch C, Maier SE, Schroth G, Lovblad K, Dierks T (2004) Pathways that make voices: white matter changes in auditory hallucinations. Arch Gen Psychiatry 61:658–668

    Article  PubMed  Google Scholar 

  22. Kalus P, Falkai P, Heinz A (2008) Structural and functional brain changes in schizophrenic disorders. Indications of early neuronal developmental disturbances? Nervenarzt 79:275–287

    Article  CAS  PubMed  Google Scholar 

  23. Kanaan R, Barker G, Brammer M, Giampietro V, Shergill S, Woolley J, Picchioni M, Toulopoulou T, McGuire P (2009) White matter microstructure in schizophrenia: effects of disorder, duration and medication. Br J Psychiatry 194:236–242

    Article  PubMed  Google Scholar 

  24. Kanaan RA, Kim JS, Kaufmann WE, Pearlson GD, Barker GJ, McGuire PK (2005) Diffusion tensor imaging in schizophrenia. Biol Psychiatry 58:921–929

    Article  PubMed  Google Scholar 

  25. Karlsgodt KH, van Erp TG, Poldrack RA, Bearden CE, Nuechterlein KH, Cannon TD (2008) Diffusion tensor imaging of the superior longitudinal fasciculus and working memory in recent-onset schizophrenia. Biol Psychiatry 63:512–518

    Article  PubMed  Google Scholar 

  26. Kay SR, Fiszbein A, Opler LA (1987) The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 13:261–276

    CAS  PubMed  Google Scholar 

  27. Koch K, Wagner G, Nenadic I, Schachtzabel C, Roebel M, Schultz C, Axer M, Reichenbach JR, Sauer H, Schlosser RG (2007) Temporal modeling demonstrates preserved overlearning processes in schizophrenia: an fMRI study. Neuroscience 146:1474–1483

    Article  CAS  PubMed  Google Scholar 

  28. Kubicki M, McCarley R, Westin CF, Park HJ, Maier S, Kikinis R, Jolesz FA, Shenton ME (2007) A review of diffusion tensor imaging studies in schizophrenia. J Psychiatr Res 41:15–30

    Article  PubMed  Google Scholar 

  29. Kubicki M, Park H, Westin CF, Nestor PG, Mulkern RV, Maier SE, Niznikiewicz M, Connor EE, Levitt JJ, Frumin M, Kikinis R, Jolesz FA, McCarley RW, Shenton ME (2005) DTI and MTR abnormalities in schizophrenia: analysis of white matter integrity. Neuroimage 26:1109–1118

    Article  CAS  PubMed  Google Scholar 

  30. Kubicki M, Westin CF, Maier SE, Frumin M, Nestor PG, Salisbury DF, Kikinis R, Jolesz FA, McCarley RW, Shenton ME (2002) Uncinate fasciculus findings in schizophrenia: a magnetic resonance diffusion tensor imaging study. Am J Psychiatry 159:813–820

    Article  PubMed  Google Scholar 

  31. Kubicki M, Westin CF, Nestor PG, Wible CG, Frumin M, Maier SE, Kikinis R, Jolesz FA, McCarley RW, Shenton ME (2003) Cingulate fasciculus integrity disruption in schizophrenia: a magnetic resonance diffusion tensor imaging study. Biol Psychiatry 54:1171–1180

    Article  PubMed  Google Scholar 

  32. Kyriakopoulos M, Bargiotas T, Barker GJ, Frangou S (2008) Diffusion tensor imaging in schizophrenia. Eur Psychiatry 23:255–273

    Article  PubMed  Google Scholar 

  33. Lee KH, Williams LM (2000) Eye movement dysfunction as a biological marker of risk for schizophrenia. Aust N Z J Psychiatry 34(Suppl):S91–S100

    Article  PubMed  Google Scholar 

  34. Meisenzahl EM, Seifert D, Bottlender R, Teipel S, Zetzsche T, Jager M, Koutsouleris N, Schmitt G, Scheuerecker J, Burgermeister B, Hampel H, Rupprecht T, Born C, Reiser M, Moller HJ, Frodl T (2009) Differences in hippocampal volume between major depression and schizophrenia: a comparative neuroimaging study. Eur Arch Psychiatry Clin Neurosci (in press)

  35. Meyer-Lindenberg A, Poline JB, Kohn PD, Holt JL, Egan MF, Weinberger DR, Berman KF (2001) Evidence for abnormal cortical functional connectivity during working memory in schizophrenia. Am J Psychiatry 158:1809–1817

    Article  CAS  PubMed  Google Scholar 

  36. Meyer JS, Obara K, Muramatsu K (1993) Diaschisis. Neurol Res 15:362–366

    CAS  PubMed  Google Scholar 

  37. Mitelman SA, Newmark RE, Torosjan Y, Chu KW, Brickman AM, Haznedar MM, Hazlett EA, Tang CY, Shihabuddin L, Buchsbaum MS (2006) White matter fractional anisotropy and outcome in schizophrenia. Schizophr Res 87:138–159

    Article  PubMed  Google Scholar 

  38. Mori S, van Zijl PCM, Wakana S, Nagae-Poetscher LM (2005) MRI atlas of human white matter. Elsevier Books, Oxford

    Google Scholar 

  39. Mukherjee P, Chung SW, Berman JI, Hess CP, Henry RG (2008) Diffusion tensor MR imaging and fiber tractography: technical considerations. AJNR Am J Neuroradiol 29:843–852

    Article  CAS  PubMed  Google Scholar 

  40. Munoz Maniega S, Lymer GK, Bastin ME, Marjoram D, Job DE, Moorhead TW, Owens DG, Johnstone EC, McIntosh AM, Lawrie SM (2008) A diffusion tensor MRI study of white matter integrity in subjects at high genetic risk of schizophrenia. Schizophr Res 106:132–139

    Article  CAS  PubMed  Google Scholar 

  41. Okugawa G, Nobuhara K, Minami T, Takase K, Sugimoto T, Saito Y, Yoshimura M, Kinoshita T (2006) Neural disorganization in the superior cerebellar peduncle and cognitive abnormality in patients with schizophrenia: a diffusion tensor imaging study. Prog Neuropsychopharmacol Biol Psychiatry 30:1408–1412

    Article  PubMed  Google Scholar 

  42. Okugawa G, Nobuhara K, Sugimoto T, Kinoshita T (2005) Diffusion tensor imaging study of the middle cerebellar peduncles in patients with schizophrenia. Cerebellum 4:123–127

    Article  PubMed  Google Scholar 

  43. Okugawa G, Nobuhara K, Takase K, Saito Y, Yoshimura M, Kinoshita T (2007) Olanzapine increases grey and white matter volumes in the caudate nucleus of patients with schizophrenia. Neuropsychobiology 55:43–46

    Article  CAS  PubMed  Google Scholar 

  44. Price G, Bagary MS, Cercignani M, Altmann DR, Ron MA (2005) The corpus callosum in first episode schizophrenia: a diffusion tensor imaging study. J Neurol Neurosurg Psychiatry 76:585–587

    Article  CAS  PubMed  Google Scholar 

  45. Price G, Cercignani M, Parker GJ, Altmann DR, Barnes TR, Barker GJ, Joyce EM, Ron MA (2008) White matter tracts in first-episode psychosis: a DTI tractography study of the uncinate fasciculus. Neuroimage 39:949–955

    Article  PubMed  Google Scholar 

  46. Reese TG, Heid O, Weisskoff RM, Wedeen VJ (2003) Reduction of eddy-current-induced distortion in diffusion MRI using a twice-refocused spin echo. Magn Reson Med 49:177–182

    Article  CAS  PubMed  Google Scholar 

  47. Rosenberger G, Kubicki M, Nestor PG, Connor E, Bushnell GB, Markant D, Niznikiewicz M, Westin CF, Kikinis R, Saykin JR, McCarley RW, Shenton ME (2009) Age-related deficits in fronto-temporal connections in schizophrenia: a diffusion tensor imaging study. Schizophr Res 102:181–188

    Article  Google Scholar 

  48. Rotarska-Jagiela A, Schonmeyer R, Oertel V, Haenschel C, Vogeley K, Linden DE (2008) The corpus callosum in schizophrenia-volume and connectivity changes affect specific regions. Neuroimage 39:1522–1532

    Article  PubMed  Google Scholar 

  49. Schlosser R, Gesierich T, Kaufmann B, Vucurevic G, Hunsche S, Gawehn J, Stoeter P (2003) Altered effective connectivity during working memory performance in schizophrenia: a study with fMRI and structural equation modeling. Neuroimage 19:751–763

    Article  PubMed  Google Scholar 

  50. Schlosser RG, Koch K, Wagner G, Nenadic I, Roebel M, Schachtzabel C, Axer M, Schultz C, Reichenbach JR, Sauer H (2008) Inefficient executive cognitive control in schizophrenia is preceded by altered functional activation during information encoding: an fMRI study. Neuropsychologia 46:336–347

    Article  PubMed  Google Scholar 

  51. Schlosser RG, Nenadic I, Wagner G, Gullmar D, von Consbruch K, Kohler S, Schultz CC, Koch K, Fitzek C, Matthews PM, Reichenbach JR, Sauer H (2007) White matter abnormalities and brain activation in schizophrenia: a combined DTI and fMRI study. Schizophr Res 89:1–11

    Article  PubMed  Google Scholar 

  52. Seok JH, Park HJ, Chun JW, Lee SK, Cho HS, Kwon JS, Kim JJ (2007) White matter abnormalities associated with auditory hallucinations in schizophrenia: a combined study of voxel-based analyses of diffusion tensor imaging and structural magnetic resonance imaging. Psychiatry Res 156:93–104

    Article  PubMed  Google Scholar 

  53. Smith SM, Jenkinson M, Johansen-Berg H, Rueckert D, Nichols TE, Mackay CE, Watkins KE, Ciccarelli O, Cader MZ, Matthews PM, Behrens TE (2006) Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage 31:1487–1505

    Article  PubMed  Google Scholar 

  54. Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TE, Johansen-Berg H, Bannister PR, De Luca M, Drobnjak I, Flitney DE, Niazy RK, Saunders J, Vickers J, Zhang Y, De Stefano N, Brady JM, Matthews PM (2004) Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage 23(Suppl 1):S208–S219

    Article  PubMed  Google Scholar 

  55. Smith SM, Nichols TE (2009) Threshold-free cluster enhancement: addressing problems of smoothing, threshold dependence and localisation in cluster inference. Neuroimage 44:83–98

    Article  PubMed  Google Scholar 

  56. Steel RM, Bastin ME, McConnell S, Marshall I, Cunningham-Owens DG, Lawrie SM, Johnstone EC, Best JJ (2001) Diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy (1H MRS) in schizophrenic subjects and normal controls. Psychiatry Res 106:161–170

    Article  CAS  PubMed  Google Scholar 

  57. Strik W, Dierks T, Hubl D, Horn H (2008) Hallucinations, thought disorders, and the language domain in schizophrenia. Clin EEG Neurosci 39:91–94

    CAS  PubMed  Google Scholar 

  58. Wager TD, Smith EE (2003) Neuroimaging studies of working memory: a meta-analysis. Cogn Affect Behav Neurosci 3:255–274

    Article  PubMed  Google Scholar 

  59. Walterfang M, McGuire PK, Yung AR, Phillips LJ, Velakoulis D, Wood SJ, Suckling J, Bullmore ET, Brewer W, Soulsby B, Desmond P, McGorry PD, Pantelis C (2008) White matter volume changes in people who develop psychosis. Br J Psychiatry 193:210–215

    Article  PubMed  Google Scholar 

  60. Walterfang M, Wood AG, Reutens DC, Wood SJ, Chen J, Velakoulis D, McGorry PD, Pantelis C (2008) Morphology of the corpus callosum at different stages of schizophrenia: cross-sectional study in first-episode and chronic illness. Br J Psychiatry 192:429–434

    Article  PubMed  Google Scholar 

  61. Walterfang M, Wood SJ, Velakoulis D, Copolov D, Pantelis C (2005) Diseases of white matter and schizophrenia-like psychosis. Aust N Z J Psychiatry 39:746–756

    PubMed  Google Scholar 

  62. Wang F, Sun Z, Du X, Wang X, Cong Z, Zhang H, Zhang D, Hong N (2003) A diffusion tensor imaging study of middle and superior cerebellar peduncle in male patients with schizophrenia. Neurosci Lett 348:135–138

    Article  CAS  PubMed  Google Scholar 

  63. Wang XJ (2001) Synaptic reverberation underlying mnemonic persistent activity. Trends Neurosci 24:455–463

    Article  CAS  PubMed  Google Scholar 

  64. Woods SW (2003) Chlorpromazine equivalent doses for the newer atypical antipsychotics. J Clin Psychiatry 64:663–667

    Article  CAS  PubMed  Google Scholar 

  65. Yoon JH, Minzenberg MJ, Ursu S, Walters R, Wendelken C, Ragland JD, Carter CS (2008) Association of dorsolateral prefrontal cortex dysfunction with disrupted coordinated brain activity in schizophrenia: relationship with impaired cognition, behavioral disorganization, and global function. Am J Psychiatry 165:1006–1014

    Article  PubMed  Google Scholar 

  66. Z’Graggen WJ, Fouad K, Raineteau O, Metz GA, Schwab ME, Kartje GL (2000) Compensatory sprouting and impulse rerouting after unilateral pyramidal tract lesion in neonatal rats. J Neurosci 20:6561–6569

    PubMed  Google Scholar 

  67. Zetzsche T, Preuss UW, Frodl T, Leinsinger G, Born C, Reiser M, Hegerl U, Moller HJ, Meisenzahl EM (2008) White matter alterations in schizophrenic patients with pronounced negative symptomatology and with positive family history for schizophrenia. Eur Arch Psychiatry Clin Neurosci 258:278–284

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft [KO 3744/1-1 to K.K.]).

Author information

Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, Friedrich-Schiller-University Jena, Jahnstr. 3, Philosophenweg 3, 07740, Jena, Germany

    Kathrin Koch, Gerd Wagner, Robert Dahnke, Claudia Schachtzabel, Christoph Schultz, Martin Roebel, Heinrich Sauer & Ralf G. M. Schlösser

  2. Medical Physics Group, Institute for Diagnostic and Interventional Radiology, Friedrich-Schiller-University Jena, Philosophenweg 3, 07740, Jena, Germany

    Daniel Güllmar & Jürgen R. Reichenbach

Authors
  1. Kathrin Koch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gerd Wagner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robert Dahnke
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Claudia Schachtzabel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christoph Schultz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Martin Roebel
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Daniel Güllmar
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jürgen R. Reichenbach
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Heinrich Sauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ralf G. M. Schlösser
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kathrin Koch.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Koch, K., Wagner, G., Dahnke, R. et al. Disrupted white matter integrity of corticopontine-cerebellar circuitry in schizophrenia. Eur Arch Psychiatry Clin Neurosci 260, 419–426 (2010). https://doi.org/10.1007/s00406-009-0087-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00406-009-0087-0

Keywords

Search

Navigation