近年來磁振造影技術不斷提升，提供可靠之高解析度腦結構與功能影像，以利醫學研究與臨床診斷應用。從過去大部分的研究論文可以發現，正常人及精神分裂症患者的之腦部結構差異通常是以單一參數加以研究探討而非以網路的角度。本篇研究主要以經由Voxel Based Morphometry處理過的灰質及白質輸入影像，然後應用joint Source Based Morphometry (jSBM)中的聯合獨立成分分析，進行分解成數個獨立成分來源（網路），然後以loading parameter之大小決定來源重要程度，從實驗結果可以發現在前額葉及顳葉的網路部分，正常人的強度比病患高。再者依照活性及負性症狀量表中的活性分數將受測者分成兩群，發現在顳葉及小腦網路與活性分數有其相關性。最後使用loading parameter與臨床分數中的威斯康辛卡片排序測驗(WCST)做結合，發現隨著該網路強度下降，WCST的錯誤率也會上升

In recent years, the rapid advance of magnetic resonance imaging technology provides the structural and functional images of brain with high resolution and high reliability. In most of previous researches, the study of difference between the normal subjects and schizophrenia patients usually focus on just one parameter model. In this study, the preprocessed images of grey matter volume and white matter volume using Voxel Based Morphometry are taken into account. Then, the joint Independent Component Analysis of a method called joint Source Based Morphometry is employed to decompose the inputs into some independent sources with their important loading parameter. From the experimental results, it is found that the networks in frontal lobe and temporal lobe are stronger in normal subjects than those in patients. In addition, basing on the values of positive scale in Positive and Negative Syndrome Scale it is found that the significant networks are correlated in temporal lobe and cerebellum. Finally, the study of the relationship between the loading parameter and the Wisconsin Card Sorting Test shows that the loading parameter and WCST total error are in inverse proportion.

[1] M. van Beilen, H. A. Kiers, A. Bou, E. H. van Zomeren, F. K. Withaar, J. Arends, et al., "Cognitive deficits and social functioning in schizophrenia: a clinical perspective," Clin Neuropsychol, vol. 17, pp. 507-14, Nov 2003.
[2] L. Ait Bentaleb, E. Stip, and M. Beauregard, "Psychopathologie et bases neurobiologiques des hallucinations auditives dans la schizophrénie," Santé mentale au Québec, vol. 25, p. 241, 2000.
[3] B. COOPER and C. HOLMES, "Previous psychiatric history as a risk factor for late-life dementia: a population-based case-control study," Age and Ageing, vol. 27, pp. 181-188, Mar 1998.
[4] E. C. Johnstone, T. J. Crow, C. D. Frith, J. Husband, and L. Kreel, "Cerebral ventricular size and cognitive impairment in chronic schizophrenia," Lancet, vol. 2, pp. 924-6, Oct 30 1976.
[5] J. L. Whitwell, "Voxel-based morphometry: an automated technique for assessing structural changes in the brain," J Neurosci, vol. 29, pp. 9661-4, Aug 5 2009.
[6] A. Mechelli, C. J. Price, K. J. Friston, and J. Ashburner, "Voxel-Based Morphometry of the Human Brain: Methods and Applications," Current Medical Imaging Reviews, vol. 1, pp. 105-113, Jun 2005.
[7] G. R. Ridgway, S. M. Henley, J. D. Rohrer, R. I. Scahill, J. D. Warren, and N. C. Fox, "Ten simple rules for reporting voxel-based morphometry studies," Neuroimage, vol. 40, pp. 1429-35, May 1 2008.
[8] C. D. Good, I. S. Johnsrude, J. Ashburner, R. N. Henson, K. J. Friston, and R. S. Frackowiak, "A voxel-based morphometric study of ageing in 465 normal adult human brains," Neuroimage, vol. 14, pp. 21-36, Jul 2001.
[9] D. CC, M. RW, V. MM, N. MA, S. LJ, H. Y, et al., "Schizotypal personality disorder and MRI abnormalities of temporal lobe grey matter," Biol Psychiatry, vol. 45, pp. 1393-402, Jun 1999.
[10] E. A. Hazlett, M. S. Buchsbaum, M. M. Haznedar, R. Newmark, K. E. Goldstein, Y. Zelmanova, et al., "Cortical grey and white matter volume in unmedicated schizotypal and schizophrenia patients," Schizophr Res, vol. 101, pp. 111-23, Apr 2008.
[11] R. J. Gurrera, M. Nakamura, M. Kubicki, C. C. Dickey, M. A. Niznikiewicz, M. M. Voglmaier, et al., "The uncinate fasciculus and extraversion in schizotypal personality disorder: a diffusion tensor imaging study," Schizophr Res, vol. 90, pp. 360-2, Feb 2007.
[12] M. E. Shenton, C. C. Dickey, M. Frumin, and R. W. McCarley, "A review of MRI findings in schizophrenia," Schizophr Res, vol. 49, pp. 1-52, Apr 15 2001.
[13] E. A. Hazlett, K. E. Goldstein, and J. C. Kolaitis, "A review of structural MRI and diffusion tensor imaging in schizotypal personality disorder," Curr Psychiatry Rep, vol. 14, pp. 70-8, Feb 2012.
[14] L. Xu, K. M. Groth, G. Pearlson, D. J. Schretlen, and V. D. Calhoun, "Source-based morphometry: the use of independent component analysis to identify grey matter differences with application to schizophrenia," Hum Brain Mapp, vol. 30, pp. 711-24, Mar 2009.
[15] V. D. Calhoun, T. Adali, L. K. Hansen, J. Larsen, and J. J. Pekar, "ICA of Functional MRI Data: an Overview," International Symposium on Independent Component Analysis and Blind Signal Separation Apr 2003.
[16] M. McKeown, "Independent component analysis of functional MRI: what is signal and what is noise?," Current Opinion in Neurobiology, vol. 13, pp. 620-629, 2003.
[17] L. Xu, G. Pearlson, and V. D. Calhoun, "Joint source based morphometry identifies linked grey and white matter group differences," Neuroimage, vol. 44, pp. 777-89, Feb 1 2009.
[18] A. Hyvarinen and E. Oja, "Independent component analysis: algorithms and applications," Neural Networks, vol. 13, pp. 411-430, May-Jun 2000.
[19] G. R. Naik and D. K. Kumar, "An Overview of Independent Component Analysis and Its Applications," Informatica, pp. 63-81, 2011.
[20] C. F. Beckmann, "Modelling with independent components," Neuroimage, vol. 62, pp. 891-901, Aug 15 2012.
[21] C. F. Beckmann and S. M. Smith, "Probabilistic independent component analysis for functional magnetic resonance imaging," Medical Imaging, IEEE Transactions on, vol. 23, pp. 137-152, 2004.
[22] V. I. Dobromyslin, D. H. Salat, C. B. Fortier, E. C. Leritz, C. F. Beckmann, W. P. Milberg, et al., "Distinct functional networks within the cerebellum and their relation to cortical systems assessed with independent component analysis," Neuroimage, vol. 60, pp. 2073-85, May 1 2012.
[23] A. R. Groves, C. F. Beckmann, S. M. Smith, and M. W. Woolrich, "Linked independent component analysis for multimodal data fusion," Neuroimage, vol. 54, pp. 2198-217, Feb 1 2011.
[24] V. D. Calhoun, T. Adali, K. A. Kiehl, R. Astur, J. J. Pekar, and G. D. Pearlson, "A method for multitask fMRI data fusion applied to schizophrenia," Hum Brain Mapp, vol. 27, pp. 598-610, Jul 2006.
[25] V. Calhoun, T. Adali, and J. Liu, "A feature-based approach to combine functional MRI, structural MRI and EEG brain imaging data," Conf Proc IEEE Eng Med Biol Soc, vol. 1, pp. 3672-5, 2006.
[26] V. D. Calhoun, T. Adali, N. R. Giuliani, J. J. Pekar, K. A. Kiehl, and G. D. Pearlson, "Method for multimodal analysis of independent source differences in schizophrenia: combining grey matter structural and auditory oddball functional data," Hum Brain Mapp, vol. 27, pp. 47-62, Jun 26 2006.
[27] K. Specht, R. Zahn, K. Willmes, S. Weis, C. Holtel, B. J. Krause, et al., "Joint independent component analysis of structural and functional images reveals complex patterns of functional reorganisation in stroke aphasia," Neuroimage, vol. 47, pp. 2057-63, Oct 1 2009.
[28] A. R. Franco, J. Ling, A. Caprihan, V. D. Calhoun, R. E. Jung, G. L. Heileman, et al., "Multimodal and Multi-tissue Measures of Connectivity Revealed by Joint Independent Component Analysis," IEEE J Sel Top Signal Process, vol. 2, pp. 986-997, Dec 1 2008.
[29] X. Guo, Y. Han, K. Chen, Y. Wang, and L. Yao, "Mapping joint grey and white matter reductions in Alzheimer's disease using joint independent component analysis," Neurosci Lett, vol. 531, pp. 136-41, Dec 7 2012.
[30] V. D. Calhoun, J. Liu, and T. Adali, "A review of group ICA for fMRI data and ICA for joint inference of imaging, genetic, and ERP data," Neuroimage, vol. 45, pp. S163-72, Mar 2009.
[31] J. Sui, T. Adali, Q. Yu, J. Chen, and V. D. Calhoun, "A review of multivariate methods for multimodal fusion of brain imaging data," J Neurosci Methods, vol. 204, pp. 68-81, Feb 15 2012.
[32] J. Ashburner and K. J. Friston, "Unified segmentation," Neuroimage, vol. 26, pp. 839-51, Jul 1 2005.
[33] J. Ashburner, "A fast diffeomorphic image registration algorithm," Neuroimage, vol. 38, pp. 95-113, Oct 15 2007.
[34] V. D. Calhoun and S. Member, "Feature-based Fusion of Medical Imaging Data," Information Technology in Biomedicine, vol. 13, pp. 711-720, Sep 2009.
[35] "An information-maximisation approach to blind separation and blind deconvolution," 1995.
[36] N. Correa, T. Adali, and V. D. Calhoun, "Performance of blind source separation algorithms for fMRI analysis using a group ICA method," Magn Reson Imaging, vol. 25, pp. 684-94, Jun 2007.
[37] H. Akaike, "A New Look at Statistical Model Identification," Automatic Control, vol. 19, 1974.
[38] V. D. Calhoun, T. Adali, G. D. Pearlson, and J. J. Pekar, "A Method for Making Group Inferences from Functional MRI Data Using Independent Component Analysis," Current Medical Imaging, pp. 140-151, Jun 2001.
[39] M. Wax and T. Kailath, "Detection of Signals by Information Theoretic Criteria," Speech and Signal Processing, vol. 33, pp. 387-392, Apr 1985.
[40] W. H. Organization. (2006). Mental health, Disorder management. Available: http://www.who.int/mental_health/management/schizophrenia/en/
[41] M. S. Keshavan and N. R. Schooler, "First-episode studies in schizophrenia: criteria and characterization," Schizophr Bull, vol. 18, pp. 491-513, 1992.
[42] J. A. Lieberman, D. Perkins, A. Belger, M. Chakos, F. Jarskog, K. Boteva, et al., "The early stages of schizophrenia: speculations on pathogenesis, pathophysiology, and therapeutic approaches," Biol Psychiatry, vol. 50, pp. 884-97, Dec 1 2001.
[43] C. M. Canuso, C. A. Bossie, J. Amatniek, I. Turkoz, G. Pandina, and B. Cornblatt, "Paliperidone extended-release tablets in patients with recently diagnosed schizophrenia," Early Interv Psychiatry, vol. 4, pp. 64-78, Feb 2010.
[44] K. Rosen and P. Garety, "Predicting recovery from schizophrenia: a retrospective comparison of characteristics at onset of people with single and multiple episodes," Schizophr Bull, vol. 31, pp. 735-50, Jul 2005.
[45] H. E. Hulshoff Pol, H. G. Schnack, M. G. Bertens, N. E. van Haren, I. van der Tweel, W. G. Staal, et al., "Volume changes in grey matter in patients with schizophrenia," Am J Psychiatry, vol. 159, pp. 244-50, Feb 2002.
[46] I. C. Wright, S. Rabe-Hesketh, P. W. Woodruff, A. S. David, R. M. Murray, and E. T. Bullmore, "Meta-analysis of regional brain volumes in schizophrenia," Am J Psychiatry, vol. 157, pp. 16-25, Jan 2000.
[47] T. Takahashi, M. Suzuki, S. Y. Zhou, R. Tanino, H. Hagino, L. Niu, et al., "Temporal lobe grey matter in schizophrenia spectrum: a volumetric MRI study of the fusiform gyrus, parahippocampal gyrus, and middle and inferior temporal gyri," Schizophr Res, vol. 87, pp. 116-26, Oct 2006.
[48] A. Pepe, L. Zhao, J. Koikkalainen, J. Hietala, U. Ruotsalainen, and J. Tohka, "Automatic statistical shape analysis of cerebral asymmetry in 3D T1-weighted magnetic resonance images at vertex-level: application to neuroleptic-naive schizophrenia," Magn Reson Imaging, vol. 31, pp. 676-87, Jun 2013.
[49] H. Ananth, I. Popescu, H. D. Critchley, C. D. Good, R. S. Frackowiak, and R. J. Dolan, "Cortical and subcortical grey matter abnormalities in schizophrenia determined through structural magnetic resonance imaging with optimized volumetric voxel-based morphometry," Am J Psychiatry, vol. 159, pp. 1497-505, Sep 2002.
[50] E. Antonova, V. Kumari, R. Morris, R. Halari, A. Anilkumar, R. Mehrotra, et al., "The relationship of structural alterations to cognitive deficits in schizophrenia: a voxel-based morphometry study," Biol Psychiatry, vol. 58, pp. 457-67, Sep 15 2005.
[51] M. Kubicki, M. E. Shenton, D. F. Salisbury, Y. Hirayasu, K. Kasai, R. Kikinis, et al., "Voxel-based morphometric analysis of grey matter in first episode schizophrenia," Neuroimage, vol. 17, pp. 1711-9, Dec 2002.
[52] M. Wilke, C. Kaufmann, A. Grabner, B. Putz, T. C. Wetter, and D. P. Auer, "Grey matter-changes and correlates of disease severity in schizophrenia: a statistical parametric mapping study," Neuroimage, vol. 13, pp. 814-24, May 2001.
[53] I. C. Wright, Z. R. Ellison, T. Sharma, K. J. Friston, R. M. Murray, and P. K. McGuire, "Mapping of grey matter changes in schizophrenia," Schizophr Res, vol. 35, pp. 1-14, Jan 4 1999.
[54] R. P. Rajarethinam, J. R. DeQuardo, R. Nalepa, and R. Tandon, "Superior temporal gyrus in schizophrenia: a volumetric magnetic resonance imaging study," Schizophr Res, vol. 41, pp. 303-12, Jan 21 2000.