Neurobiologische Fundierung von Sprach- und Denkstörungen bei Patienten mit Schizophrenie

Zusammenfassung

Störungen der Sprache und des Denkens sind Kernsymptome der Schizophrenie. Untersuchungen mit strukturellen und funktionellen bildgebenden Methoden (fMRT) sowie Magnetenzephalographie (MEG) zu Sprachprozessen bei Patienten mit Schizophrenie geben Hinweise auf deren Pathogenese. In einem Erklärungsmodell für sprachvermittelte kognitive Defizite und psychopathologische Symptome werden verschiedene Beschreibungs- und Befundebenen integriert. Positive Formale Denkstörungen gehen mit einer „funktionellen” Läsion im linken G. temp. sup., einem Teil der Wernicke-Area, einher. Dem zugrunde liegen eine interne Störung des semantischen Netzes, das durch ein Sprachlateralisationsdefizit im lateralen Temporallappen bei Patienten verursacht wird. Weiterhin liegen den formalen Denkstörungen ein gestörtes verbales Selbst-Monitoring zugrunde. Normalerweise werden Sprachfehler präartikulatorisch korrigiert und das Verbesserte artikuliert. Dieser Fehlerdetektions- und Korrektionsmechanismus, der vor allem im linken sulcus temp. sup. in Verbindung gebracht wurde, ist bei Patienten gestört. Formalen Denkstörungen liegen komplexe kognitive und zerebrale Prozesse zugrunde, die wir gerade erst zu verstehen beginnen.

Abstract

Alterations in thought and language are core symptoms of schizophrenia. Studies with structural and functional imaging (fMRI) as well as magneto/electroencephalography (EEG, MEG) on language in schizophrenia are reviewed which will help to reveal the correlates of formal thought disorder (FTD) and concretism. A model will be presented, where brain structure, function, receptorchemistry, cognitive deficits and psychopathology of language related phenomena are integrated. Positive formal thought disorder is correlated with a “functional” lesion in the superior temporal gyrus, part of Wernickes area. There is secondly a dysfunction of the semantic network, which is due to a language lateralisation deficit in the lateral temporal lobe in FTD. Further, a dysfunctional verbal self monitoring and error correction process in part responsible for FTD. Taken together, there is much evidence that the lateral temporal lobes bilaterally are predominantly involved in the generation of positive formal thought disorder in schizophrenia.

Schlüsselwörter

Schizophrenie - fMRT - formale Denkstörungen

Key words

schizophrenia - fMRI - formal thought disorder - language - speech - concretism

Literatur

• 1 Kircher T. Psychopathologie und Hirnfunktion.  Nervenheilkunde. 2002;  21 336-343
• 2 Kircher T. Neuronale Korrelate psychopathologischer Symptome. Denk- und Sprachprozesse bei Gesunden und Patienten mit Schizophrenie. Darmstadt: Steinkopff 2003
• 3 Kircher T TJ, Bullmore E T, Brammer M J, Williams S CR, Broome M R, Murray R M, McGuire P K. Differential activation of temporal cortex during sentence completion in schizophrenic patients with and without formal thought disorder.  Schizophr Res. 2001;  50 27-40
• 4 Tononi G, Sporns O, Edelman G M. A measure for brain complexity: relating functional segregation and integration in the nervous system.  Proc Natl Acad Sci U S A. 1994;  91 5033-5037
• 5 Pauen M. Grundprobleme der Philosophie des Geistes. Eine Einführung. Frankfurt: Fischer Taschenbuchverlag 2001
• 6 Kircher T TJ, David A S. The Self in Neuroscience and Psychiatry. Cambridge, UK: Cambridge University Press 2003
• 7 Roth G. Das Gehirn und seine Wirklichkeit. Frankfurt: Suhrkamp 1997
• 8 Habel U, Posse S, Schneider F. Funktionelle Kernspintomographie in der klinischen Psychologie und Psychiatrie.  Fortschr Neurol Psychiatr. 2002;  70 61-70
• 9 Logothetis N K, Pauls J, Augath M, Trinath T, Oeltermann A. Neurophysiological investigation of the basis of the fMRI signal.  Nature. 2001;  412 150-157
• 10 Faber R, Abrams R, Taylor M A, Kasprison A, Morris C, Weisz R. Comparison of schizophrenic patients with formal thought disorder and neurologically impaired patients with aphasia.  Am J Psychiatry. 1983;  140 1348-1351
• 11 Liddle P F, Ngan E, Caissie S, Anderson C, Bates A, Quested D, White R, Weg R. Thought and Language Index: an instrument for assessing thought and language in schizophrenia.  Br J Psychiatry. 2002;  181 326-330
• 12 Kircher T TJ, Liddle P F, Brammer M J, Williams S CR, Murray R M, McGuire P K. Neural correlates of formal thought disorder in schizophrenia.  Arch Gen Psychiatry. 2001;  58 769-774
• 13 McGuire P K, Quested D J, Spence S A, Murray R M, Frith C D, Liddle P F. Pathophysiology of "positive" thought disorder in schizophrenia.  Br J Psychiatry. 1998;  173 231-235
• 14 Kircher T, Liddle P, Brammer M, Murray R, McGuire P. Neuronale Korrelate „negativer” formaler Denkstörungen.  Nervenarzt. 2003;  74 748-754
• 15 Kircher T, Schneider F, Sauer H, Buchkremer G. Funktionelle Bildgebung in der Psychiatrie. Deutsches Ärzteblatt 2004; im Druck
• 16 Shenton M E, Dickey C C, Frumin M, McCarley R W. A review of MRI findings in schizophrenia.  Schizophr Res. 2001;  49 1-52
• 17 Gaser C, Nenadic I, Volz H P, Büchel C, Sauer H. Neuroanatomy of „Hearing Voices”: A Frontotemporal Brain Structural Abnormality Associated with Auditory Hallucinations in Schizophrenia. Cereb Cortex 2004; in press
• 18 Falkai P, Bogerts B, Schneider T, Greve B, Pfeiffer U, Pilz K, Gonsiorzcyk C, Majtenyi C, Ovary I. Disturbed planum temporale asymmetry in schizophrenia. A quantitative post-mortem study.  Schizophr Res. 1995;  14 161-176
• 19 Manschreck T C, Maher B A, Milavetz J J, Ames D, Weisstein C C, Schneyer M L. Semantic priming in thought disordered schizophrenic patients.  Schizophr Res. 1988;  1 61-66
• 20 Spitzer M, Braun U, Maier S, Hermle L, Maher B A. Indirect semantic priming in schizophrenic patients.  Schizophr Res. 1993;  11 71-80
• 21 Kircher T TJ, Liddle P F, Brammer M J, Williams S CR, Murray R M, McGuire P K. Reversed lateralisation of temporal activation during speech production in thought disordered patients with schizophrenia.  Psychol Med. 2002;  32 439-449
• 22 Kircher T TJ, Brammer M J, Williams S CR, McGuire P K. Lexical retrieval during fluent speech production: an fmri study.  Neuroreport. 2000;  11 4093-4096
• 23 St George M, Kutas M, Martinez A, Sereno M I. Semantic integration in reading: engagement on the right hemisphere during discourse processing.  Brain. 1999;  122 1317-1325
• 24 Faust M, Chiarello C. Sentence context and lexical ambiguity resolution by the two hemispheres.  Neuropsychologia. 1998;  36 827-835
• 25 Beeman M. Semantic processing in the right hemisphere may contribute to drawing inferences from discourse.  Brain Lang. 1993;  44 80-120
• 26 Spitzer M, Braun U, Hermle L, Maier S. Associative semantic network dysfunction in thought-disordered schizophrenic patients: direct evidence from indirect semantic priming.  Biol Psychiatry. 1993;  34 864-877
• 27 Weisbrod M, Maier S, Harig S, Himmelsbach U, Spitzer M. Lateralised semantic and indirect semantic priming effects in people with schizophrenia.  Br J Psychiatry. 1998;  172 142-146
• 28 Blakemore S J, Frith C D. Disorders of Self-Monitoring and the Symptoms of Schizophrenia. In: Kircher T, David A (eds). The Self in Neuroscience and Psychiatry. Cambridge, UK: Cambridge University Press 2003
• 29 Jeannerod M, Farrer M, Franck N, Fourneret P, Posada A, Daprati E, Georgieff N. Action recognition in normal and schizophrenic subjects. In: Kircher T, David A (eds). The Self in Neuroscience and Psychiatry. Cambridge, UK: Cambridge University Press 2003
• 30 Levelt W JM. Speaking. From Intention to Articulation. 1 ed. Cambridge, MA; London, England: MIT Press 1989
• 31 Knoblich G, Stottmeister F, Kircher T TJ. Self-monitoring in Schizophrenia. Psychol Med 2004; in press
• 32 Knoblich G, Kircher T. Deceiving oneself about control: Sensitivity for mapping changes between movements and their consequences. J Exp Psychol Hum Percept Perform 2004; in press
• 33 Leube D T, Knoblich G, Erb M, Grodd W, Bartels M, Kircher T TJ. The neural correlates for Identifying One's Own Movements.  Neuroimage. 2003;  20 2084-2090
• 34 Kircher T TJ, Brammer M J, Levelt W J, Bartels M, McGuire P K. Pausing for thought: activation of left temporal cortex during pauses in speech.  Neuroimage. 2004;  21 84-90
• 35 Rapp A, Leube D T, Erb M, Grodd W, Kircher T TJ. Neural correlates of metaphor processing. Cognit Brain Res 2004; in press
• 36 Kircher T TJ, Leube D, Erb M, Ackermann H, Grodd W, Rapp A. Processing of metaphors in schizophrenia. in Vorbereitung
• 37 Kircher T T, Bullmore E T, Brammer M J, Williams S C, Broome M R, Murray R M, McGuire P K. Differential activation of temporal cortex during sentence completion in schizophrenic patients with and without formal thought disorder.  Schizophr Res. 2001;  50 27-40
• 38 Strik W. Psychiatrische Neurophysiologie. In: Helmchen H, Henn F, Lauter H, Sartorius N (eds). Psychiatrie der Gegenwart, Bd. 1, Grundlagen der Psychiatrie. Berlin, Heidelberg, New York: Springer 1999: 251-275
• 39 Umbricht D, Koller R, Schmid L, Skrabo A, Grubel C, Huber T, Stassen H. How specific are deficits in mismatch negativity generation to schizophrenia?.  Biol Psychiatry. 2003;  53 1120-1131
• 40 Hirayasu Y, Potts G F, O'Donnell B F, Kwon J S, Arakaki H, Akdag S J, Levitt J J, Shenton M E, McCarley R W. Auditory mismatch negativity in schizophrenia: topographic evaluation with a high-density recording montage.  Am J Psychiatry. 1998;  155 1281-1284
• 41 Youn T, Park H J, Kim J J, Kim M S, Kwon J S. Altered hemispheric asymmetry and positive symptoms in schizophrenia: equivalent current dipole of auditory mismatch negativity.  Schizophr Res. 2003;  59 253-260
• 42 Park H J, Kwon J S, Youn T, Pae J S, Kim J J, Kim M S, Ha K S. Statistical parametric mapping of LORETA using high density EEG and individual MRI: application to mismatch negativities in Schizophrenia.  Hum Brain Mapp. 2002;  17 168-178
• 43 Sauer H, Rosburg T, Kreitschmann Andermahr I, Volz H P, Huonker R, Nowak H, Hajek M. Geschlechtsspezifische Unterschiede der Hemisphärenlateralisation bei Schizophrenien? Eine MEG-MRT-Studie.  Nervenarzt. 1998;  69 249-256
• 44 Hall D A, Haggard M P, Akeroyd M A, Palmer A R, Summerfield A Q, Elliott M R, Gurney E M, Bowtell R W. “Sparse” temporal sampling in auditory fMRI.  Hum Brain Mapp. 1999;  7 213-223
• 45 Le T H, Patel S, Roberts T P. Functional MRI of human auditory cortex using block and event-related designs.  Magn Reson Med. 2001;  45 254-260
• 46 Kircher T TJ, Rapp A, Grodd W, Buchkremer G, Weiskopf N, Lutzenberger W, Ackermann H, Mathiak K. Mismatch responses in schizophrenia: a combined fMRI and whole-head MEG study.  Am J Psychiatry. 2004;  161 294-304
• 47 Mathiak K, Rapp A, Kircher T TJ, Grodd W, Hertrich I, Weiskopf N, Lutzenberger W, Ackermann H. Mismatch response to randomized gradient switching noise as reflected by fMRI and whole-head magnetoencephalography.  Hum Brain Mapp. 2002;  16 190-195
• 48 Umbricht D, Schmid L, Koller R, Vollenweider F X, Hell D, Javitt D C. Ketamine-induced deficits in auditory and visual context-dependent processing in healthy volunteers: implications for models of cognitive deficits in schizophrenia.  Arch Gen Psychiatry. 2000;  57 1139-1147
• 49 Olney J W, Farber N B. Glutamate receptor dysfunction and schizophrenia.  Arch Gen Psychiatry. 1995;  52 998-1007
• 50 Sherman A D, Hegwood T S, Baruah S, Waziri R. Deficient NMDA-mediated glutamate release from synaptosomes of schizophrenics.  Biol Psychiatry. 1991;  30 1191-1198
• 51 Akbarian S, Sucher N J, Bradley D, Tafazzoli A, Trinh D, Hetrick W P, Potkin S G, Sandman C A, Bunney W-E J, Jones E G. Selective alterations in gene expression for NMDA receptor subunits in prefrontal cortex of schizophrenics.  J Neurosci. 1996;  16 19-30
• 52 Humphries C, Mortimer A, Hirsch S, de Belleroche J. NMDA receptor mRNA correlation with antemortem cognitive impairment in schizophrenia.  Neuroreport. 1996;  7 2051-2055
• 53 Naatanen R. The perception of speech sounds by the human brain as reflected by the mismatch negativity (MMN) and its magnetic equivalent (MMNm).  Psychophysiology. 2001;  38 1-21
• 54 Michie P T. What has MMN revealed about the auditory system in schizophrenia?.  Int J Psychophysiol. 2001;  42 177-194
• 55 Kircher T. Sprache, Gehirn und Schizophrenie.  Nervenheilkunde. 2003;  5 245-252
• 56 Jakob H, Beckmann H. Prenatal developmental disturbances in the limbic allocortex in schizophrenics.  J Neural Transm. 1986;  65 303-326
• 57 Perrone-Bizzozero N I, Sower A C, Bird E D, Benowitz L I, Ivins K J, Neve R L. Levels of the growth-associated protein GAP-43 are selectively increased in association cortices in schizophrenia.  Proc Natl Acad Sci USA. 1996;  93 14 182-14 187
• 58 Fatemi S H. Reelin mutations in mouse and man: from reeler mouse to schizophrenia, mood disorders, autism and lissencephaly.  Mol Psychiatry. 2001;  6 129-133
• 59 Impagnatiello F, Guidotti A R, Pesold C, Dwivedi Y, Caruncho H, Pisu M G, Uzunov D P, Smalheiser N R, Davis J M, Pandey G N, Pappas G D, Tueting P, Sharma R P, Costa E. A decrease of reelin expression as a putative vulnerability factor in schizophrenia.  Proc Natl Acad Sci U S A. 1998;  95 15 718-15 723
• 60 Jones P, Rodgers B, Murray R, Marmot M. Child development risk factors for adult schizophrenia in the British 1946 birth cohort.  Lancet. 1994;  344 1398-1402
• 61 Orr K G, Cannon M, Gilvarry C M, Jones P B, Murray R M. Schizophrenic patients and their first-degree relatives show an excess of mixed-handedness.  Schizophr Res. 1999;  39 167-176
• 62 Taylor P, Dalton R, Fleminger J J. Handedness and schizophrenic symptoms.  Br J Med Psychol. 1982;  55 287-291
• 63 Manoach D S, Maher B A, Manschreck T C. Left-handedness and though disorder in the schizophrenias.  J Abnorm Psychol. 1988;  97 97-99
• 64 Cardno A G, Sham P C, Murray R M, McGuffin P. Twin study of symptom dimensions in psychoses.  Br J Psychiatry. 2001;  179 39-45
• 65 Shergill S S, Brammer M J, Williams S CR, Murray R M, McGuire P K. Mapping auditory hallucinations in schizophrenia using functional magnetic resonance imaging.  Arch Gen Psychiatry. 2000;  57 1033-1038
• 66 Dierks T, Linden D E, Jandl M, Formisano E, Goebel R, Lanfermann H, Singer W. Activation of Heschl's gyrus during auditory hallucinations.  Neuron. 1999;  22 615-621
• 67 Silbersweig D A, Stern E, Frith C, Cahill C, Holmes A, Grootoonk S, Seaward J, McKenna P, Chua S E, Schnorr L. et al . A functional neuroanatomy of hallucinations in schizophrenia.  Nature. 1995;  378 176-179
• 68 McGuire P K, Shah G M, Murray R M. Increased blood flow in Broca's area during auditory hallucinations in schizophrenia.  Lancet. 1993;  342 703-706
• 69 Suzuki M, Yuasa S, Minabe Y, Murata M, Kurachi M. Left superior temporal blood flow increases in schizophrenic and schizophreniform patients with auditory hallucination: a longitudinal case study using 123I-IMP SPECT.  Eur Arch Psychiatry Clin Neurosci. 1993;  242 257-261
• 70 Kircher T, Gauggel S. Neuropsychologie der Schizophrenie. Symptome, Kognition, Gehirn. Berlin, Heidelberg: Springer Verlag 2007