Abstract
A number of recent studies have combined multiple experimental paradigms and modalities to find relevant biological markers for schizophrenia. In this study, we extracted fMRI features maps from the analysis of three experimental paradigms (auditory oddball, Sternberg item recognition, sensorimotor) for a large number (n = 154) of patients with schizophrenia and matched healthy controls. We used the general linear model (GLM) and independent component analysis (ICA) to extract feature maps (i.e. ICA component maps and GLM contrast maps), which were then subjected to a coefficient-constrained independent component analysis (CCICA) to identify potential neurobiological markers. A total of 29 different feature maps were extracted for each subject. Our results show a number of optimal feature combinations that reflect a set of brain regions that significantly discriminate between patients and controls in the spatial heterogeneity and amplitude of their feature signals. Spatial heterogeneity was seen in regions such as the superior/middle temporal and frontal gyri, bilateral parietal lobules, and regions of the thalamus. Most strikingly, an ICA feature representing a bilateral frontal pole network was consistently seen in the ten highest feature results when ranked on differences found in the amplitude of their feature signals. The implication of this frontal pole network and the spatial variability which spans regions comprising of bilateral frontal/temporal lobes and parietal lobules suggests that they might play a significant role in the pathophysiology of schizophrenia.
Similar content being viewed by others
References
Andreasen, N. C. (Ed.). (1983). Scale for the Assessment of Negative Symptoms (SANS). Iowa City: University of Iowa.
Andreasen, N. C. (Ed.). (1984). Scale for the Assessment of Positive Symptoms (SAPS). Iowa City: University of Iowa.
Antonova, E., Kumari, V., Morris, R., Halari, R., Anilkumar, A., Mehrotra, R., et al. (2005). The relationship of structural alterations to cognitive deficits in schizophrenia: a voxel-based morphometry study. Biological Psychiatry, 58(6), 457–467.
Barta, P. E., Pearlson, G. D., Powers, R. E., Richards, S. S., & Tune, L. E. (1990). Auditory hallucinations and smaller superior temporal gyral volume in schizophrenia. The American Journal of Psychiatry, 147(11), 1457–1462.
Beckmann, C. F., DeLuca, M., Devlin, J. T., & Smith, S. M. (2005). Investigations into resting-state connectivity using independent component analysis. Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences, 360(1457), 1001–1013.
Bell, A. J., & Sejnowski, T. J. (1995). An information-maximization approach to blind separation and blind deconvolution. Neural Computation, 7(6), 1129–1159.
Broyd, S. J., Demanuele, C., Debener, S., Helps, S. K., James, C. J., & Sonuga-Barke, E. J. (2008). Default-mode brain dysfunction in mental disorders: A systematic review. Neuroscience and Biobehavioral Reviews
Calhoun, V. D., Adali, T., Pearlson, G. D., & Pekar, J. J. (2001). A Method for Making Group Inferences from Functional MRI Data Using Independent Component Analysis. Human Brain Mapping, 14(3), 140–151.
Calhoun, V. D., Adali, T., Giuliani, N. R., Pekar, J. J., Kiehl, K. A., & Pearlson, G. D. (2006). Method for multimodal analysis of independent source differences in schizophrenia: combining gray matter structural and auditory oddball functional data. Human Brain Mapping, 27(1), 47–62.
Calhoun, V. D., Kiehl, K. A., Pearlson, G. D. (2007a). Modulation of temporally coherent brain networks estimated using ICA at rest and during cognitive tasks. Hum Brain Mapp In Press.
Calhoun, V. D., Maciejewski, P. K., Pearlson, G. D., Kiehl, K. A. (2007b). Temporal lobe and “default” hemodynamic brain modes discriminate between schizophrenia and bipolar disorder. Human Brain Mapping
Calhoun, V. D., Kiehl, K. A., Pearlson, G. D. (2008). Modulation of temporally coherent brain networks estimated using ICA at rest and during cognitive tasks. Human Brain Mapping.
Caprihan, A., Pearlson, G. D., & Calhoun, V. D. (2008). Application of principal component analysis to distinguish patients with schizophrenia from healthy controls based on fractional anisotropy measurements. Neuroimage, 42(2), 675–682.
Davidson, L. L., & Heinrichs, R. W. (2003). Quantification of frontal and temporal lobe brain-imaging findings in schizophrenia: a meta-analysis. Psychiatry Research, 122(2), 69–87.
Ford, J. M. (1999). Schizophrenia: the broken P300 and beyond. Psychophysiology, 36(6), 667–682.
Freire, L., Roche, A., & Mangin, J. F. (2002). What is the best similarity measure for motion correction in fMRI time series? IEEE Transactions on Medical Imaging, 21(5), 470–484.
Friedman, L., & Glover, G. H. (2006). Reducing interscanner variability of activation in a multicenter fMRI study: controlling for signal-to-fluctuation-noise-ratio (SFNR) differences. Neuroimage, 33(2), 471–481.
Friedman, L., Stern, H., Brown, G. G., Mathalon, D. H., Turner, J., Glover G. H., et al. (2007). Test-retest and between-site reliability in a multicenter fMRI study. Human Brain Mapping.
Friston, K. (1994). Statistical parametric mapping.
Friston, K. J. (1999). Schizophrenia and the disconnection hypothesis. Acta Psychiatrica Scandinavica. Supplementum, 395, 68–79.
Garrity, A. G., Pearlson, G. D., McKiernan, K., Lloyd, D., Kiehl, K. A., & Calhoun, V. D. (2007). Aberrant “default mode” functional connectivity in schizophrenia. The American Journal of Psychiatry, 164(3), 450–457.
Glahn, D. C., Ragland, J. D., Abramoff, A., Barrett, J., Laird, A. R., Bearden, C. E., et al. (2005). Beyond hypofrontality: a quantitative meta-analysis of functional neuroimaging studies of working memory in schizophrenia. Human Brain Mapping, 25(1), 60–69.
Goldman-Rakic, P. S. (1994). Working memory dysfunction in schizophrenia. The Journal of Neuropsychiatry and Clinical Neurosciences, 6(4), 348–357.
Goldman-Rakic, P. S., & Selemon, L. D. (1997). Functional and anatomical aspects of prefrontal pathology in schizophrenia. Schizophrenia Bulletin, 23(3), 437–458.
Groom, M. J., Jackson, G. M., Calton, T. G., Andrews, H. K., Bates, A. T., Liddle, P. F., et al. (2008). Cognitive deficits in early-onset schizophrenia spectrum patients and their non-psychotic siblings: a comparison with ADHD. Schizophrenia Research, 99(1–3), 85–95.
Hill, K., Mann, L., Laws, K. R., Stephenson, C. M., Nimmo-Smith, I., & McKenna, P. J. (2004). Hypofrontality in schizophrenia: a meta-analysis of functional imaging studies. Acta Psychiatrica Scandinavica, 110(4), 243–256.
Himberg, J., Hyvarinen, A., & Esposito, F. (2004). Validating the independent components of neuroimaging time series via clustering and visualization. Neuroimage, 22(3), 1214–1222.
Kiehl, K. A., Stevens, M., Laurens, K. R., Pearlson, G. D., Calhoun, V. D., & Liddle, P. F. (2005a). An adaptive reflexive processing model of neurocognitive function: Supporting evidence from a large scale (n = 100) fMRI study of an auditory oddball task. Neuroimage, 25, 899–915.
Kiehl, K. A., Stevens, M. C., Celone, K., Kurtz, M., & Krystal, J. H. (2005b). Abnormal hemodynamics in schizophrenia during an auditory oddball task. Biological Psychiatry, 57(9), 1029–1040.
Kim, D. I., Manoach, D. S., Mathalon, D. H., Turner, J. A., Mannell, M., Brown, G. G., et al. (2009a). Dysregulation of working memory and default-mode networks in schizophrenia using independent component analysis, an fBIRN and MCIC study. Human Brain Mapping.
Kim, D. I., Mathalon, D. H., Ford, J. M., Mannell, M., Turner, J. A., Brown, G. G., et al. (2009b). Auditory Oddball Deficits in Schizophrenia: An Independent Component Analysis of the fMRI Multisite Function BIRN Study. Schizophrenia Bulletin, 35(1), 67–81.
Kindermann, S. S., Karimi, A., Symonds, L., Brown, G. G., & Jeste, D. V. (1997). Review of functional magnetic resonance imaging in schizophrenia. Schizophrenia Research, 27(2–3), 143–156.
Laurens, K. R., Kiehl, K. A., Ngan, E. T., & Liddle, P. F. (2005). Attention orienting dysfunction during salient novel stimulus processing in schizophrenia. Schizophrenia Research, 75(2–3), 159–171.
Lee, J., & Park, S. (2005). Working memory impairments in schizophrenia: a meta-analysis. Journal of Abnormal Psychology, 114(4), 599–611.
Li, Y. O., Adali, T., & Calhoun, V. D. (2007). Estimating the number of independent components for functional magnetic resonance imaging data. Human Brain Mapping, 28(11), 1251–1266.
Machado, G., Juarez, M., Clark, V. P., Gollub, R. L., Magnotta, V., White, T., et al. (2007). Probing schizophrenia with a sensorimotor task: Large-scale (n = 273) independent component analysis of first episode and chronic schizophrenia patients.
Manoach, D. S. (2003). Prefrontal cortex dysfunction during working memory performance in schizophrenia: reconciling discrepant findings. Schizophrenia Research, 60(2–3), 285–298.
Manoach, D. S., Gollub, R. L., Benson, E. S., Searl, M. M., Goff, D. C., Halpern, E., et al. (2000). Schizophrenic subjects show aberrant fMRI activation of dorsolateral prefrontal cortex and basal ganglia during working memory performance. Biological Psychiatry, 48(2), 99–109.
Meda, S. A., Bhattarai, M., Morris, N. A., Astur, R. S., Calhoun, V. D., Mathalon, D. H., et al. (2008). An fMRI study of working memory in first-degree unaffected relatives of schizophrenia patients. Schizophrenia Research, 104(1–3), 85–95.
Meisenzahl, E. M., Koutsouleris, N., Bottlender, R., Scheuerecker, J., Jager, M., Teipel, S. J., et al. (2008). Structural brain alterations at different stages of schizophrenia: a voxel-based morphometric study. Schizophrenia Research, 104(1–3), 44–60.
Meyer-Lindenberg, A., Poline, J. B., Kohn, P. D., Holt, J. L., Egan, M. F., Weinberger, D. R., et al. (2001). Evidence for abnormal cortical functional connectivity during working memory in schizophrenia. The American Journal of Psychiatry, 158(11), 1809–1817.
Minzenberg, M. J., Laird, A. R., Thelen, S., Carter, C. S., & Glahn, D. C. (2009). Meta-analysis of 41 functional neuroimaging studies of executive function in schizophrenia. Archives of General Psychiatry, 66(8), 811–822.
Park, H. J., Levitt, J., Shenton, M. E., Salisbury, D. F., Kubicki, M., Kikinis, R., et al. (2004). An MRI study of spatial probability brain map differences between first-episode schizophrenia and normal controls. Neuroimage, 22(3), 1231–1246.
Pearlson, G. D. (1997). Superior temporal gyrus and planum temporale in schizophrenia: a selective review. Progress in Neuropsychopharmacology & Biological Psychiatry, 21(8), 1203–1229.
Quintana, J., Wong, T., Ortiz-Portillo, E., Kovalik, E., Davidson, T., Marder, S. R., et al. (2003). Prefrontal-posterior parietal networks in schizophrenia: primary dysfunctions and secondary compensations. Biological Psychiatry, 53(1), 12–24.
Schneider, F., Habel, U., Reske, M., Kellermann, T., Stocker, T., Shah, N. J., et al. (2007). Neural correlates of working memory dysfunction in first-episode schizophrenia patients: an fMRI multi-center study. Schizophrenia Research, 89(1–3), 198–210.
Schroder, J., Essig, M., Baudendistel, K., Jahn, T., Gerdsen, I., Stockert, A., et al. (1999). Motor dysfunction and sensorimotor cortex activation changes in schizophrenia: A study with functional magnetic resonance imaging. Neuroimage, 9(1), 81–87.
Schwarz, J. C. (1971). High School Yearbooks: Further explication and reply to Meehl. Journal of Abnormal Psychology, 78(2), 145–147.
Sternberg, S. (1966). High-speed scanning in human memory. Science, 153(736), 652–654.
Sui, J., Adali, T., Pearlson, G. D., & Calhoun, V. D. (2009a). An ICA-based method for the identification of optimal FMRI features and components using combined group-discriminative techniques. Neuroimage, 46(1), 73–86.
Sui, J., Adali, T., Pearlson, G. D., Clark, V. P., & Calhoun, V. D. (2009b). A method for accurate group difference detection by constraining the mixing coefficients in an ICA framework. Human Brain Mapping.
Xu, L., Groth, K. M., Pearlson, G., Schretlen, D. J., & Calhoun, V. D. (2009). Source-based morphometry: the use of independent component analysis to identify gray matter differences with application to schizophrenia. Human Brain Mapping, 30(3), 711–724.
Acknowledgements
This work was supported by the National Institutes of Health; Contract grant number: 1 RO1 EB 006841. We would like to personally thank Christopher Abbott for his insightful comments on this manuscript.
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Kim, D.I., Sui, J., Rachakonda, S. et al. Identification of Imaging Biomarkers in Schizophrenia: A Coefficient-constrained Independent Component Analysis of the Mind Multi-site Schizophrenia Study. Neuroinform 8, 213–229 (2010). https://doi.org/10.1007/s12021-010-9077-7
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12021-010-9077-7