Abstract
It has been long recognized that schizophrenia, unlike certain other mental disorders, appears to be delocalized, i.e., difficult to attribute to a dysfunction of a few specific brain areas, and may be better understood as a disruption of brain’s emergent network properties. In this chapter, we focus on topological properties of functional brain networks obtained from fMRI data, and demonstrate that some of those properties can be used as discriminative features of schizophrenia in multivariate predictive setting. While the prior work on schizophrenia networks has been primarily focused on discovering statistically significant differences in network properties, this work extends the prior art by exploring the generalization (prediction) ability of network models for schizophrenia, which is not necessarily captured by such significance tests. Moreover, we show that significant disruption of the topological and spatial structure of functional MRI networks in schizophrenia (a) cannot be explained by a disruption to area-based task-dependent responses, i.e., indeed relates to the emergent properties, (b) is global in nature, affecting most dramatically long-distance correlations, and (c) can be leveraged to achieve high classification accuracy (93%) when discriminating between schizophrenic vs. control subjects based just on a single fMRI experiment using a simple auditory task.
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References
Friston K, Frith C (1995) Schizophrenia: a disconnection syndrome? Clin Neurosci 3(2):89–97
Stephan K, Friston K, Frith C (2009) Dysconnection in schizophrenia: from abnormal synaptic plasticity to failures of self-monitoring. Schizophr Bull 35:509–527. doi:10.1093/schbul/sbn176
Wernicke C (1906) Grundrisse der psychiatrie. Verlag von Georg Thieme, Leipzig
Bleuler E (1911) Dementia praecox or the group of schizophrenias. International Universities Press, New York, NY
Garrity A, Pearlson GD, McKiernan K, Lloyd D, Kiehl K et al (2007) Aberrant “default mode” functional connectivity in schizophrenia. Am J Psychiatry 164:450–457. doi:10.1176/appi.ajp.164.3.450
Bassett D, Bullmore E, Verchinski B, Mattay V, Weinberger D et al (2008) Hierarchical organization of human cortical networks in health and schizophrenia. J Neurosci 28(37):9239–9248. doi:10.1523/jneurosci.1929-08.2008
Liu Y, Liang M, Zhou Y, He Y, Hao Y et al (2008) Disrupted small-world networks in schizophrenia. Brain 131:945–961. doi:10.1093/brain/awn018
Eguiluz V, Chialvo D, Cecchi G, Baliki M, Apkarian A (2005) Scale-free functional brain networks. Phys Rev Lett 94:018102
Rish I, Cecchi G, Thyreau B, Thirion B, Plaze M, Paillere-Martinot ML, Martelli C, Martinot JL, Poline JB (2013) Schizophrenia as a network disease: disruption of emergent brain function in patients with auditory hallucinations. PLoS One 8(1):e50625. Public Library of Science
Lo A, Chernoff H, Zheng T, Lo SH (2015) Why signifcant variables arent automatically good predictors. Proc Natl Acad Sci U S A 112(45):13892–13897
Plaze M, Bartrs-Faz D, Martinot J, Januel D, Bellivier F et al (2006) Left superior temporal gyrus activation during sentence perception negatively correlates with auditory hallucination severity in schizophrenia patients. Schizophr Res 87(1–3):109–115. doi:10.1016/j.schres.2006.05.005
Cecchi G, Rish I, Thyreau B, Thirion B, Plaze M, et al. (2009) Discriminiative network models of schizophrenia. In: Proc. of NIPS-09
Rish I, Cecchi GA, Heuton K (2012) Schizophrenia classification using fMRI-based functional net-work features. In: Proc. of SPIE Medical Imaging 2012
Woods S (2003) Chlorpromazine equivalent doses for the newer atypical antipsychotics. J Clin Psychiatry 64:663–667
Banerjee O, El Ghaoui L, d’Aspremont A (2008) Model selection through sparse maximum likelihood estimation for multivariate gaussian or binary data. J Mach Learn Res 9:485–516
Meyer-Lindenberg A, Poline JB, Kohn P, Holt J, Egan M et al (2001) Evidence for abnormal cor-tical functional connectivity duringworking memory in schizophrenia. Am J Psychiatry 158(11):1809–1817
Zhou Y, Liang M, Tian L, Wang K, Hao Y et al (2007) Functional disintegration in paranoid schizophrenia using resting-state fMRI. Schizophr Res 97:194–205. doi:10.1016/j.schres.2007.05.029
Bluhm R, Miller J, Lanius R, Osuch E, Boksman K et al (2007) Spontaneous low-frequencyuctu-ations in the BOLD signal in schizophrenic patients: anomalies in the default network. Schizophr Bull 33:1004–1012. doi:10.1093/schbul/sbm052
Micheloyannis S, Pachou E, Stam C, Breakspear M, Bitsios P et al (2006) Small-world networks and disturbed functional connectivity in schizophrenia. Schizophr Res 87:60–66. doi:10.1016/j.schres.2006.06.028
Whitfield-Gabrieli S, Thermenos H, Milanovic S, Tsuang M, Faraone S et al (2009) Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degree relatives of persons with schizophrenia. Proc Natl Acad Sci U S A 106:1279–1284. doi:10.1073/pnas.0809141106
Sui QYJ, Rachakonda S, He H, Gruner W, Pearlson G et al (2011) Altered topological properties of functional network connectivity in schizophrenia during resting state: a small-world brain network study. PLoS One 6:e25423. doi:10.1371/journal.pone.0025423
Friston K, Harrison L, Penny W (2003) Dynamic causal modelling. NeuroImage 19(4):1273–1302. doi:10.1016/s1053-8119(03)00202-7
Zhang L, Samaras D, Alia-Klein N, Volkow N, Goldstein R (2006) Modeling neuronal interactivity using dynamic bayesian networks. In: Advances in neural information processing systems 18. MIT Press, Cambridge MA, pp 1593–1600
Storkey AJ, Simonotto E, Whalley H, Lawrie S, Murray L et al (2007) Learning structural equa-tion models for fMRI. In: Advances in neural information processing systems 19. MIT Press, Cambridge MA, pp 1329–1336
Kircher T, Oh T, Brammer M, McGuire P (2005) Neural correlates of syntax production in schizophrenia. Br J Psychiatry 186:209–214. doi:10.1192/bjp.186.3.209
Benedetti F, Poletti S, Radaelli D, Bernasconi A, Cavallaro R et al (2010) Temporal lobe grey matter volume in schizophrenia is associated with a genetic polymorphism inuencing glycogen synthase kinase 3-β activity. Genes Brain Behav 9:365–371. doi:10.1111/j.1601-183x.2010.00566.x
Lawrie S, Buechel C, Whalley H, Frith C, Friston K et al (2002) Reduced frontotemporal func-tional connectivity in schizophrenia associated with auditory hallucinations. Biol Psychiatry 51:10081011. doi:10.1016/s0006-3223(02)01316-1
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Rish, I., Cecchi, G.A. (2017). Functional Network Disruptions in Schizophrenia. In: Tatarinova, T., Nikolsky, Y. (eds) Biological Networks and Pathway Analysis. Methods in Molecular Biology, vol 1613. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7027-8_19
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DOI: https://doi.org/10.1007/978-1-4939-7027-8_19
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