Association between abnormal brain functional connectivity in children and psychopathology: A study based on graph theory and machine learning

Abstract

Objectives: One of the major challenges facing psychiatry is how to incorporate biological measures in the classification of mental health disorders. Many of these disorders affect brain development and its connectivity.

In this study, we propose a novel method for assessing brain networks based on the combination of a graph theory measure (eigenvector centrality) and a one-class support vector machine (OC-SVM).

Methods: We applied this approach to resting-state fMRI data from 622 children and adolescents. Eigenvector centrality (EVC) of nodes from positive- and negative-task networks were extracted from each subject and used as input to an OC-SVM to label individual brain networks as typical or atypical. We hypothesised that classification of these subjects regarding the pattern of brain connectivity would predict the level of psychopathology.

Results: Subjects with atypical brain network organisation had higher levels of psychopathology (p < 0.001). There was a greater EVC in the typical group at the bilateral posterior cingulate and bilateral posterior temporal cortices; and significant decreases in EVC at left temporal pole.

Conclusions: The combination of graph theory methods and an OC-SVM is a promising method to characterise neurodevelopment, and may be useful to understand the deviations leading to mental disorders.

Keywords:

• Connectivity
• children
• psychopathology
• machine learning
• fMRI

Acknowledgements

The opinions, hypothesis, conclusions and recommendations of this study are under the responsibility of the authors, which does not necessarily represent the opinion of the funding agencies. The authors are grateful to Sao Paulo Research Foundation - FAPESP (J.R.S grants 2013/10498-6, 2013/00506-1 and A.J. 2013/08531-5), CAPES and CNPq, Brazil for funding this research. This is a study from the National Institutes of Science and Technology for Developmental Psychiatry of Children and Adolescents (INPD) supported by CNPq (573974/2008-0) and FAPESP (2008/57896-8). A.Z. receives a studentship from CAPES-Brazil. G.A.S. receives a CAPES/FAPERGS post-doctoral scholarship. M.Q.H. receives a FAPESP post-doctoral scholarship (2013/16864-4).

Disclosure statement

Dr. Luis Augusto Rohde has been on the speakers’ bureau/advisory board and/or acted as consultant for Eli-Lilly, Janssen-Cilag, Novartis and Shire in the last 3 years. The ADHD and Juvenile Bipolar Disorder Outpatient Programmes chaired by him received unrestricted educational and research support from the following pharmaceutical companies in the last 3 years: Eli-Lilly, Janssen-Cilag, Novartis, and Shire. He receives authorship royalties from Oxford Press and ArtMed. Dr. Rodrigo A.Bressan has been on the speakers’ bureau/advisory board of AstraZeneca, Bristol, Janssen and Lundbeck; he has received research grants from Janssen, Eli-Lilly, Lundbeck, Novartis, Roche, FAPESP, CNPq, CAPES, Fundação E.J. Safra and Fundação ABAHDS. He is a shareholder of Biomolecular Technology Ltda. Edson Amaro Jr has received research grants from FAPESP, CNPq, CAPES, Fundação E.J. Safra and Fundação ABAHDS.

All other authors reported no biomedical financial interests or potential conflicts of interest.

Additional information

Funding

The authors are grateful to Sao Paulo Research Foundation - FAPESP [J.R.S grants 2013/10498-6, 2013/00506-1 and A.J. 2013/08531-5]; CAPES and CNPq, Brazil for funding this research. This is a study from the National Institutes of Science and Technology for Developmental Psychiatry of Children and Adolescents (INPD) supported by CNPq [573974/2008-0] and FAPESP [2008/57896-8]. A.Z. receives a studentship from CAPES-Brazil. G.A.S. receives a CAPES/FAPERGS post-doctoral scholarship. M.Q.H. receives a FAPESP post-doctoral scholarship [2013/16864-4].