Identification of segregated regions in the functional brain connectome of autistic patients by a combination of fuzzy spectral clustering and entropy analysis

Identification of segregated regions in the functional brain connectome of autistic patients by a combination of fuzzy spectral clustering and entropy analysis

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J Psychiatry Neurosci 2016;41(2):124-132

João Ricardo Sato, PhD; Joana Balardin, PhD; Maciel Calebe Vidal, MSc; André Fujita, PhD

Abstract

Background: Several neuroimaging studies support the model of abnormal development of brain connectivity in patients with autism-spectrum disorders (ASD). In this study, we aimed to test the hypothesis of reduced functional network segregation in autistic patients compared with controls.

Methods: Functional MRI data from children acquired under a resting-state protocol (Autism Brain Imaging Data Exchange [ABIDE]) were submitted to both fuzzy spectral clustering (FSC) with entropy analysis and graph modularity analysis.

Results: We included data from 814 children in our analysis. We identified 5 regions of interest comprising the motor, temporal and occipitotemporal cortices with increased entropy (p < 0.05) in the clustering structure (i.e., more segregation in the controls). Moreover, we noticed a statistically reduced modularity (p < 0.001) in the autistic patients compared with the controls. Significantly reduced eigenvector centrality values (p < 0.05) in the patients were observed in the same regions that were identified in the FSC analysis. Limitations: There is considerable heterogeneity in the fMRI acquisition protocols among the sites that contributed to the ABIDE data set (e.g., scanner type, pulse sequence, duration of scan and resting-state protocol). Moreover, the sites differed in many variables related to sample characterization (e.g., age, IQ and ASD diagnostic criteria). Therefore, we cannot rule out the possibility that additional differences in functional network organization would be found in a more homogeneous data sample of individuals with ASD.

Conclusion: Our results suggest that the organization of the whole-brain functional network in patients with ASD is different from that observed in controls, which implies a reduced modularity of the brain functional networks involved in sensorimotor, social, affective and cognitive processing.


Submitted Dec. 5, 2014; Revised Apr. 22, 2015; Revised June 2, 2015; Accepted July 2, 2015; Early-released Oct. 27, 2015

Acknowledgements: This work was supported by FAPESP (2014/09576-5, 2013/01715-3, 2011/50761-2), CNPq (304020/2013-3, 473063/2013-1), NAP eScience – PRP – USP, and CAPES.

Affiliations: From the Center of Mathematics, Computation, and Cognition, Universidade Federal do ABC, Santo André, SP, Brazil (Sato, Balardin); and the Department of Computer Science, Institute of Mathematics and Statistics, University of São Paulo, São Paulo, SP, Brazil (Vidal, Fujita).

Competing interests: None declared.

Contributors: J. Sato, M. Vidal and A. Fujita designed the study. J. Sato, J. Balardin and A. Fujita analyzed the data (acquired elsewhere) and wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.140364

Correspondence to: A. Fujita, Rua do Matão, 1010 – Cidade Universitária, São Paulo – SP, 05508-090, Brazil; fujita@ime.usp.br