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Structural and metabolic changes in language areas linked to formal thought disorder

  • Helge Horn (a1), Andrea Federspiel (a1), Miranka Wirth (a1), Thomas J. Müller (a1), Roland Wiest (a2), Jiong-Jiong Wang (a3) and Werner Strik (a1)...
Abstract
Background

The role of the language network in the pathophysiology of formal thought disorder has yet to be elucidated.

Aims

To investigate whether specific grey-matter deficits in schizophrenic formal thought disorder correlate with resting perfusion in the left-sided language network.

Method

We investigated 13 right-handed patients with schizophrenia and formal thought disorder of varying severity and 13 matched healthy controls, using voxel-based morphometry and magnetic resonance imaging perfusion measurement (arterial spin labelling).

Results

We found positive correlations between perfusion and the severity of formal thought disorder in the left frontal and left temporoparietal language areas. We also observed bilateral deficits in grey-matter volume, positively correlated with the severity of thought disorder in temporoparietal areas and other brain regions. The results of the voxel-based morphometry and the arterial spin labelling measurements overlapped in the left posterior superior temporal gyrus and left angular gyrus.

Conclusions

Specific grey-matter deficits may be a risk factor for state-related dysfunctions of the left-sided language system, leading to local hyperperfusion and formal thought disorder.

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Copyright
Corresponding author
Dr Helge Horn, University Hospital of Psychiatry, Bolligenstrasse 111, CH-3000, Bern 60, Switzerland. Email: horn@puk.unibe.ch
Footnotes
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These authors contributed equally to the work.

Declaration of interest

None.

Funding detailed in Acknowledgements.

Footnotes
References
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1 Phillips, ML. The emerging role of neuroimaging in psychiatry: characterizing treatment-relevant endophenotypes. Am J Psychiatry 2007; 164: 697–9.
2 McGuire, PK, Quested, DJ, Spence, SA, Murray, RM, Frith, CD, Liddle, PF. Pathophysiology of ‘positive’ thought disorder in schizophrenia. Br J Psychiatry 1998; 173: 231–5.
3 Kircher, TT, Liddle, PF, Brammer, MJ, Williams, SC, Murray, RM, McGuire, PK. Neural correlates of formal thought disorder in schizophrenia: preliminary findings from a functional magnetic resonance imaging study. Arch Gen Psychiatry 2001; 58: 769–74.
4 Kircher, TT, Liddle, PF, Brammer, MJ, Williams, SC, Murray, RM, McGuire, PK. Reversed lateralization of temporal activation during speech production in thought disordered patients with schizophrenia. Psychol Med 2002; 32: 439–49.
5 Shenton, ME, Kikinis, R, Jolesz, FA, Pollak, SD, LeMay, M, Wible, CG, Hokama, H, Martin, J, Metcalf, D, Coleman, M. Abnormalities of the left temporal lobe and thought disorder in schizophrenia. A quantitative magnetic resonance imaging study. N Engl J Med 1992; 327: 604–12.
6 Stirling, J, Hellewell, J, Blakey, A, Deakin, W. Thought disorder in schizophrenia is associated with both executive dysfunction and circumscribed impairments in semantic function. Psychol Med 2006; 36: 475–84.
7 Kerns, JG, Berenbaum, H. Cognitive impairments associated with formal thought disorder in people with schizophrenia. J Abnorm Psychol 2002; 111: 211–24.
8 Vita, A, Dieci, M, Giobbio, GM, Caputo, A, Ghiringhelli, L, Comazzi, M, Garbarini, M, Mendini, AP, Morganti, C, Tenconi, F. Language and thought disorder in schizophrenia: brain morphological correlates. Schizophr Res 1995; 15: 243–51.
9 Subotnik, KL, Bartzokis, G, Green, MF, Nuechterlein, KH. Neuroanatomical correlates of formal thought disorder in schizophrenia. Cognit Neuropsychiatry 2003; 8: 81–8.
10 Jung-Beeman, M. Bilateral brain processes for comprehending natural language. Trends Cogn Sci 2005; 9: 512–8.
11 Heim, S. The structure and dynamics of normal language processing: insights from neuroimaging. Acta Neurobiol Exp (Wars) 2005; 65: 95116.
12 Liddle, PF, Friston, KJ, Frith, CD, Hirsch, SR, Jones, T, Frackowiak, RS. Patterns of cerebral blood flow in schizophrenia. Br J Psychiatry 1992; 160: 179–86.
13 Ebmeier, KP, Blackwood, D, Murray, C, Souza, V, Walker, M, Dougall, N, Moffoot, A, O'Carroll, R, Goodwin, G. Single-photon emission tomography with 99mTc-exametazime in unmedicated schizophrenic patients. Biol Psychiatry 1993; 33: 487–95.
14 Sabri, O, Erkwoh, R, Schreckenberger, M, Owega, A, Sass, H, Buell, U. Correlation of positive symptoms exclusively to hyperperfusion or hypoperfusion of cerebral cortex in never-treated schizophrenics. Lancet 1997; 349: 1735–9.
15 Lahti, AC, Weiler, MA, Holcomb, HH, Tamminga, CA, Carpenter, WT, McMahon, R. Correlations between rCBF and symptoms in two independent cohorts of drug-free patients with schizophrenia. Neuropsychopharmacology 2006; 31: 221–30.
16 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (4th edn) (DSM–IV). APA, 1994.
17 World Health Organization. The ICD–10 Classification of Mental and Behavioural Disorders. WHO, 1992.
18 Oldfield, RC. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 1971; 9: 97113.
19 Woods, SW. Chlorpromazine equivalent doses for the newer atypical antipsychotics. J Clin Psychiatry 2003; 64: 663–7.
20 Kay, SR, Fiszbein, A, Opler, LA. The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophr Bull 1987; 13: 261–76.
21 Andreasen, N, Grove, W. Thought, language and communication in schizophrenia: diagnosis and prognosis. Schizophr Bull 1986; 12: 348–59.
22 Good, CD, Johnsrude, IS, Ashburner, J, Henson, RN, Friston, KJ, Frackowiak, RS. A voxel-based morphometric study of ageing in 465 normal adult human brains. Neuroimage 2001; 14: 2136.
23 Honea, R, Crow, TJ, Passingham, D, Mackay, CE. Regional deficits in brain volume in schizophrenia: a meta-analysis of voxel-based morphometry studies. Am J Psychiatry 2005; 162: 2233–45.
24 Luh, WM, Wong, EC, Bandettini, PA, Hyde, JS. QUIPSS II with thin-slice TI1 periodic saturation: a method for improving accuracy of quantitative perfusion imaging using pulsed arterial spin labeling. Magn Reson Med 1999; 41: 1246–54.
25 Wong, EC, Buxton, RB, Frank, LR. Implementation of quantitative perfusion imaging techniques for functional brain mapping using pulsed arterial spin labeling. NMR Biomed 1997; 10: 237–49.
26 Federspiel, A, Muller, TJ, Horn, H, Kiefer, C, Strik, WK. Comparison of spatial and temporal pattern for fMRI obtained with BOLD and arterial spin labeling. J Neural Transm 2006; 113: 1403–15.
27 Wang, J, Rao, H, Wetmore, GS, Furlan, PM, Korczykowski, M, Dinges, DF, Detre, JA. Perfusion functional MRI reveals cerebral blood flow pattern under psychological stress. Proc Natl Acad Sci USA 2005; 102: 17804–9.
28 Forman, SD, Cohen, JD, Fitzgerald, M, Eddy, WF, Mintun, MA, Noll, DC. Improved assessment of significant activation in functional magnetic resonance imaging (fMRI): use of a cluster-size threshold. Magn Reson Med 1995; 33: 636–47.
29 Jones, DK, Symms, MR, Cercignani, M, Howard, RJ. The effect of filter size on VBM analyses of DT-MRI data. Neuroimage 2005; 26: 546–54.
30 May, A. The role of imaging in the pathophysiology and diagnosis of headache. Curr Opin Neurol 2005; 18: 293–7.
31 Leonhardt, G, de Greiff, A, Weber, J, Ludwig, T, Wiedemayer, H, Forsting, M, Hufnagel, A. Brain perfusion following single seizures. Epilepsia 2005; 46: 1943–9.
32 Saygin, AP, Dick, F, Wilson, SM, Dronkers, NF, Bates, E. Neural resources for processing language and environmental sounds: evidence from aphasia. Brain 2003; 126: 928–45.
33 Vigneau, M, Beaucousin, V, Herve, PY, Duffau, H, Crivello, F, Houde, O, Mazoyer, B, Tzourio-Mazoyer, N. Meta-analyzing left hemisphere language areas: phonology, semantics, and sentence processing. Neuroimage 2006; 30:1414–32.
34 Dronkers, NF, Wilkins, DP, Van, VR, Redfern, BB, Jaeger, JJ. Lesion analysis of the brain areas involved in language comprehension. Cognition 2004; 92: 145–77.
35 Kreher, DA, Holcomb, PJ, Goff, D, Kuperberg, GR. Neural evidence for faster and further automatic spreading activation in schizophrenic thought disorder. Schizophr Bull 2008; 34: 473–82.
36 Lewis, DA, Moghaddam, B. Cognitive dysfunction in schizophrenia: convergence of gamma-aminobutyric acid and glutamate alterations. Arch Neurol 2006; 63: 1372–6.
37 Daskalakis, ZJ, Fitzgerald, PB, Christensen, BK. The role of cortical inhibition in the pathophysiology and treatment of schizophrenia. Brain Res Rev 2007; 56: 427–42.
38 Jones, EG. GABAergic neurons and their role in cortical plasticity in primates. Cereb Cortex 1993; 3: 361–72.
39 Catani, M, Howard, RJ, Pajevic, S, Jones, DK. Virtual in vivo interactive dissection of white matter fasciculi in the human brain. Neuroimage 2002; 17: 7794.
40 Hagoort, P. On Broca, brain, and binding: a new framework. Trends Cogn Sci 2005; 9: 416–23.
41 Coulson, S, Williams, RF. Hemispheric asymmetries and joke comprehension. Neuropsychologia 2005; 43: 128–41.
42 Hutsler, J, Galuske, RA. Hemispheric asymmetries in cerebral cortical networks. Trends Neurosci 2003; 26: 429–35.
43 Crow, TJ. Schizophrenia as the price that Homo sapiens pays for language: a resolution of the central paradox in the origin of the species. Brain Res Brain Res Rev 2000; 31: 118–29.
44 Van Veen, V, Carter, CS. Error detection, correction, and prevention in the brain: a brief review of data and theories. Clin EEG Neurosci 2006; 37: 330–5.
45 Cavanna, AE, Trimble, MR. The precuneus: a review of its functional anatomy and behavioural correlates. Brain 2006; 129: 564–83.
46 Buijs, PC, Krabbe-Hartkamp, MJ, Bakker, CJ, de Lange, EE, Ramos, LM, Breteler, MM, Mali, WP. Effect of age on cerebral blood flow: measurement with ungated two-dimensional phase-contrast MR angiography in 250 adults. Radiology 1998; 209: 667–74.
47 Raz, N, Rodrigue, KM. Differential aging of the brain: patterns, cognitive correlates and modifiers. Neurosci Biobehav Rev 2006; 30: 730–48.
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Structural and metabolic changes in language areas linked to formal thought disorder

  • Helge Horn (a1), Andrea Federspiel (a1), Miranka Wirth (a1), Thomas J. Müller (a1), Roland Wiest (a2), Jiong-Jiong Wang (a3) and Werner Strik (a1)...
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eLetters

Re: Neural correlates of formal thought disorder

Helge Horn, consultant psychiatrist
17 April 2009

We welcome interest in our study of structural and metabolic changes in language areas linked to formal thought disorder (FTD). Palaniyappan suggest to use the Thought and Language Index (TLI) instead of the Thought, Language and Communication scale (TLC) in order to quantify FTD. The TLI, she argues, would have the advantage over the TLC of a standardized method of eliciting thought flow. Unfortunately, the TLI was established after the start of our study (Liddle, P. F., Ngan, E. T., Caissie, S. L. et al, 2002) whereas the TLC was an established instrument that has been successfully used in numerous studies as a reliable instrument to quantify FTD (Andreasen, NC and Grove, W, 1986). We agree that future studies might benefit from the application of the more standardized TLI. However, the distribution of the severity of FTD in the patient group should not change substantially, just by changing from TLC to TLI. Therefore, we regard our results as reliable.

Furthermore Palaniyappan criticizes the factor analysis of the PANSS in small patient samples used in neuroimaging studies. She is right that afactor analytic approach in such small samples is critical, if the patients group is randomly selected. In order to be able to study FTD withneuroimaging techniques we recruited a specifically selected patient sample, which manly differs in the severity of FTD and barely in other psychopathological categories. To obtain such selected sample the recruitment took years. Patients were matched for all other psychopathology beside the items of FTD of the PANSS as good as possible. The factor analysis and the correlation of the factors with the severity of FTD were only used to document this special patient selection. Therefore, it is no surprise, that the factors of our factor analysis do not match the factors of unselected sample of schizophrenic patients (Fitzgerald, P. B., de Castella, A. R., Brewer, K. et al, 2003). To study specific psychopathological phenomena like FTD by means of Neuroimaging, such a specific selection of patients is necessary to extract reliable results. In our patient group we did not observe any significant correlation between FTD and i) positive symptoms (without PANSS item P2): r=0.39; p=0.19, and ii) negative symptoms (without PANSS item N5): r= 0.04; p= 0.90. We therefore can exclude that our results are due to positive or negative symptoms in general.

Concerning the issue of the sample size in neuroimaging studies our results were corrected for multiple comparisons. This approach is a commonand accepted way to handle this problem in neuroimaging studies in general.

Andreasen, NC and Grove, W (1986) Thought, language and communicationin schizophrenia: diagnosis and prognosis. schizophr.Bull., 12, 348-359.

Fitzgerald, P. B., de Castella, A. R., Brewer, K., et al (2003) A confirmatory factor analytic evaluation of the pentagonal PANSS model. Schizophr.Res., 61, 97-104.

Liddle, P. F., Ngan, E. T., Caissie, S. L., et al (2002) Thought and Language Index: an instrument for assessing thought and language in schizophrenia. Br.J.Psychiatry, 181, 326-330.

Declaration of interest: None
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Conflict of interest: None Declared

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Neural correlates of formal thought disorder

Lena Palaniyappan, Academic Clinical Fellow
19 February 2009

Horn et al (2009) investigate a very important, somewhat underexplored area of neural correlates of schizophrenic speech disturbance. Given the probability of underlying deficits in contextual integration and theory of mind, formal thought disorder (FTD) yields a fertile ground for structural and functional connectivity analysis in schizophrenia. While the use of hitherto unused techniques such as restingperfusion scan to study FTD must be lauded, the results of this preliminary study must be treated with caution for various reasons.

The composite score of Thought, Language and Communication scale(TLC)has been used as a measure of severity of FTD. The authors have administered the scale 45 minutes before the scanning procedure for each subject. It is widely perceived that uncontrolled generation of thought isrequired to reliably measure FTD in schizophrenia. TLC itself lacks a standardised practical method of eliciting such thought flow in contrast to some recently developed instruments (Liddle, Ngan, Caissie, et al,2002). The cross-sectional use of TLC to measure severity of FTD must be treated with prudence.

The authors extract components from Positive and Negative Syndrome Scale (PANSS) using factor analysis and demonstrate that none of these components correlate with severity of FTD as measured by total score of TLC. The validity of factor analysis in such a small sample is questionable and not in synchrony with available factorial structures of PANSS (Fitzgerald, de Castella, Brewer, et al, 2003). As a result, all principal components extracted were from negative symptoms in PANSS (except the conceptual disorganisation item, which was rightly excluded from further analysis). Consequently the results only show a lack of correlation between severity of FTD and negative symptoms as measured by PANSS. The MRI findings may still be explained by positive symptoms alone and not by FTD.Lastly, the pervasive issue of sample size in neuroimaging studies becomesmore prominent when correlation analyses are attempted in whole brain analyses.

Fitzgerald, P. B., de Castella, A. R., Brewer, K., et al (2003) A confirmatory factor analytic evaluation of the pentagonal PANSS model. Schizophrenia Research, 61, 97-104.

Horn, H., Federspiel, A., Wirth, M., et al (2009)Structural and metabolic changes in language areas linked to formal thought disorder. TheBritish Journal of Psychiatry, 194, 130-138.

Liddle, P. F., Ngan, E. T. C., Caissie, S. L., et al (2002) Thought and Language Index: an instrument for assessing thought and language in schizophrenia. The British Journal of Psychiatry, 181, 326-330.

Declaration of interest: None
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Conflict of interest: None Declared

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