Skip to main content
Log in

Schizophrenie als Diskonnektionssyndrom

Studien mit funktioneller Magnetresonanztomographie und Strukturgleichungsmodellen

Schizophrenia as a disconnection syndrome. Studies with functional magnetic resonance imaging and structural equation modeling

  • Funktionelle Bildgebung in der Psychiatrie
  • Published:
Der Radiologe Aims and scope Submit manuscript

Zusammenfassung

Neben der charakteristischen psychopathologischen Symptomatik stellen kognitive Defizite ein zentrales Merkmal der Schizophrenie dar. Diese Defizite können nur im Kontext miteinander interagierender Hirnareale verstanden werden. Zur Untersuchung dieser funktionellen Wechselbeziehungen wurden Strukturgleichungsmodelle („structural equation modeling“, SEM) zur Auswertung von fMRT-Datensätzen verwendet. In einer Untersuchungsreihe bei schizophrenen Patienten ergab sich sowohl bei antipsychotisch behandelten als auch bei unbehandelten Patienten ein Muster gesteigerter thalamokortikaler funktioneller Konnektivität als Hinweis auf eine mögliche Störung fronto-striato-thalamo-kortikaler Regelkreise. Unbehandelte Patienten und Patienten unter typischen Antipsychotika zeichneten sich zudem durch eine reduzierte interhemisphärische kortikokortikale Konnektivität aus. Dieser Unterschied zu den Gesunden war bei den Patienten unter atypischen Antipsychotika nicht mehr in dieser Ausprägung zu beobachten, was als Ausdruck einer möglichen positiven Beeinflussung der Informationsverarbeitung bei Patienten unter Atypika interpretiert werden könnte. Die erhaltenen Ergebnisse sind konsistent mit dem Modell der Schizophrenie als einem Diskonnektionssyndrom und früheren Konzeptionen einer „kognitiven Dysmetrie“ als Grundlage kognitiver Defizite bei dieser Erkrankung.

Abstract

Aside from characteristic psychopathological symptoms, cognitive deficits are a core feature of schizophrenia. These deficits can only be addressed within the context of widespread functional interactions among different brain areas. To examine these interactions, structural equation modeling (SEM) was used for the analysis of fMRI datasets. In a series of studies, both in antipsychotic-treated and drug-free schizophrenic patients, a pattern of enhanced thalamocortical functional connectivity could be observed as an indicator for possible disruptions of frontostriatal thalamocortical circuitry. Moreover, drug-free patients and those receiving typical antipsychotic drugs were characterized by reduced interhemispheric corticocortical connectivity. This difference relative to normal controls was less in patients under atypical antipsychotic drugs. The results could be interpreted as a beneficial effect of atypical antipsychotic drugs on information processing in schizophrenic patients. The present findings are consistent with the model of schizophrenia as a disconnection syndrome and earlier concepts of “cognitive dysmetria” in schizophrenia.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2
Abb. 3
Abb. 4

Literatur

  1. Alexander G, DeLong M, Strick P (1986) Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Ann Rev Neurosci 9:357–381

    Article  CAS  PubMed  Google Scholar 

  2. Alexander GE, Crutcher MD, DeLong MR (1990) Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, „prefrontal“ and „limbic“ functions. Prog Brain Res 85:119–146

    CAS  PubMed  Google Scholar 

  3. Andreasen NC (2000) Schizophrenia: the fundamental questions. Brain Res Brain Res Rev 31:106–112

    Article  Google Scholar 

  4. Andreasen NC, Nopoulos P, O’Leary DS, Miller DD, Wassink T, Flaum M (1999) Defining the phenotype of schizophrenia: cognitive dysmetria and its neural mechanisms. Biol Psychiatry 46:908–920

    Article  Google Scholar 

  5. Büchel C, Coull J, Friston K (1999) The predictive value of changes in effective connectivity for human learning. Science 283:1538–1541

    Article  CAS  PubMed  Google Scholar 

  6. Cohen MS (1997) Parametric analysis of fMRI data using linear systems methods. Neuroimage 6:93–103

    Article  CAS  PubMed  Google Scholar 

  7. Crespo-Facorro B, Paradiso S, Andreasen NC, O’Leary DS, Watkins GL, Boles Ponto LL, Hichwa RD (1999) Recalling word lists reveals „cognitive dysmetria“ in schizophrenia: a positron emission tomography study. Am J Psychiatry 156:386–392

    Google Scholar 

  8. Della-Maggiore V, Sekuler AB, Grady CL, Bennett PJ, Sekuler R, McIntosh AR (2000) Corticolimbic interactions associated with performance on a short-term memory task are modified by age. J Neurosci 20:8410–8416

    Google Scholar 

  9. 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  Google Scholar 

  10. Friston KJ (1994) Functional and effective connectivity in neuroimaging: a synthesis. Human Brain Mapping 2:56–78

    Article  Google Scholar 

  11. Friston KJ, Frith CD (1995) Schizophrenia: a disconnection syndrome? Clin Neurosci 3:89–97

    Google Scholar 

  12. Friston KJ, Holmes AP, Poline JB, Grasby PJ, Williams SC, Frackowiak RS, Turner R (1995) Analysis of fMRI time-series revisited. Neuroimage 2:45–53

    Article  CAS  PubMed  Google Scholar 

  13. Friston K, Ashburner J, Frith C, Poline J, Heather J, Frackowiak R (1995) Spatial registration and normalization of images. Hum Brain Map 2:165–189

    Google Scholar 

  14. Friston KJ, Harrison L, Penny W (2003) Dynamic causal modelling. Neuroimage 19:1273–1302

    Article  Google Scholar 

  15. Honey GD, Bullmore ET, Soni W, Varatheesan M, Williams SC, Sharma T (1999) Differences in frontal cortical activation by a working memory task after substitution of risperidone for typical antipsychotic drugs in patients with schizophrenia. Proc Natl Acad Sci USA 96:13432–13437

    Article  Google Scholar 

  16. Honey G, Fu C, Kim J, Brammer M, Croudace T, Suckling J, Pich E, Williams S, Bullmore E (2002) Effects of verbal working memory load on corticocortical connectivity modeled by path analysis of functional magnetic resonance imaging data. Neuroimage 17:573

    Article  Google Scholar 

  17. Horwitz B, Tagamets MA, McIntosh AR (1999) Neural modeling, functional brain imaging, and cognition. Trends Cogn Sci 3:91–98

    Article  Google Scholar 

  18. Jennings JM, McIntosh AR, Kapur S, Zipursky RB, Houle S (1998) Functional network differences in schizophrenia: a rCBF study of semantic processing. Neuroreport 9:1697–1700

    Google Scholar 

  19. Koenig T, Lehmann D, Saito N, Kuginuki T, Kinoshita T, Koukkou M (2001) Decreased functional connectivity of EEG theta-frequency activity in first-episode, neuroleptic-naive patients with schizophrenia: preliminary results. Schizophr Res 50:55–60

    Article  Google Scholar 

  20. Kraepelin E (1896) Psychiatrie—Ein Lehrbuch für Studierende und Ärzte. Barth, Leipzig

  21. McIntosh AR, Gonzalez Lima F (1994) Network interactions among limbic cortices, basal forebrain, and cerebellum differentiate a tone conditioned as a Pavlovian excitor or inhibitor: fluorodeoxyglucose mapping and covariance structural modeling. J Neurophysiol 72:1717–1733

    Google Scholar 

  22. Mechelli A, Price CJ, Noppeney U, Friston KJ (2003) A dynamic causal modeling study on category effects: bottom-up or top-down mediation? J Cogn Neurosci 15:925–934

    Article  Google Scholar 

  23. Meisenzahl EM, Schlösser R (2001) Functional magnetic resonance imaging research in psychiatry. Neuroimaging Clin North Am 11:365–374

    Google Scholar 

  24. Middleton FA, Strick PL (2000) Basal ganglia and cerebellar loops: motor and cognitive circuits. Brain Res Brain Res Rev 31:236–250

    Article  Google Scholar 

  25. Petersson KM, Reis A, Askelof S, Castro-Caldas A, Ingvar M (2000) Language processing modulated by literacy: a network analysis of verbal repetition in literate and illiterate subjects. J Cogn Neurosci 12:364–382

    Article  Google Scholar 

  26. Petrides M (1994) Frontal lobes and working memory: evidence from investigations of the effects of cortical excisions in nonhuman primates. In: Boller F, Grafman J (eds) Handbook of neuropsychology. Elsevier, Amsterdam, pp 59–82

  27. Rapoport M, van Reekum R, Mayberg H (2000) The role of the cerebellum in cognition and behavior: a selective review. J Neuropsychiatry Clin Neurosci 12:193–198

    Google Scholar 

  28. Rowe J, Stephan KE, Friston K, Frackowiak R, Lees A, Passingham R (2002) Attention to action in Parkinson’s disease: impaired effective connectivity among frontal cortical regions. Brain 125:276–289

    Article  Google Scholar 

  29. Schlösser R, Brodie JD (2001) Functional brain imaging in psychiatry. In: Henn F, Sartorius A, Helmchen H, Lauter H (eds) Contemporary psychiatry. Springer, Berlin Heidelberg New York, pp 179–207

  30. Schlösser R, Gesierich T, Kaufmann B, Vucurevic G, Stoeter P (2003) Funktionelle und effektive Konnektivität: Neue Analyseansätze für funktionelle bildgebende Verfahren. Nervenheilkunde 21:351–355

    Google Scholar 

  31. Schlösser R, Gesierich T, Kaufmann B, Vucurevic G, Stoeter P (2003) Altered effective connectivity in drug free schizophrenic patients. Neuroreport 14:2233–2237

    Article  Google Scholar 

  32. Schlösser 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  Google Scholar 

  33. Stern CE, Owen AM, Tracey I, Look RB, Rosen BR, Petrides M (2000) Activity in ventrolateral and mid-dorsolateral prefrontal cortex during nonspatial visual working memory processing: evidence from functional magnetic resonance imaging. Neuroimage 11:392–399

    Article  Google Scholar 

  34. Talairach J, Tournoux P (1988) Co-planar stereotaxic atlas of the human brain. Thieme, Stuttgart

  35. Weinberger DR (1987) Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry 44:660–669

    CAS  PubMed  Google Scholar 

Download references

Interessenkonflikt:

Der korrespondierende Autor versichert, dass keine Verbindungen mit einer Firma, deren Produkt in dem Artikel genannt ist, oder einer Firma, die ein Konkurrenzprodukt vertreibt, bestehen.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to R. Schlösser.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schlösser, R., Wagner, G., Köhler, S. et al. Schizophrenie als Diskonnektionssyndrom . Radiologe 45, 137–143 (2005). https://doi.org/10.1007/s00117-004-1160-3

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00117-004-1160-3

Schlüsselwörter

Keywords

Navigation