Title
Deriving reproducible biomarkers from multi-site resting-state data: An Autism-based example.
Abstract
Resting-state functional Magnetic Resonance Imaging (R-fMRI) holds the promise to reveal functional biomarkers of neuropsychiatric disorders. However, extracting such biomarkers is challenging for complex multi-faceted neuropathologies, such as autism spectrum disorders. Large multi-site datasets increase sample sizes to compensate for this complexity, at the cost of uncontrolled heterogeneity. This heterogeneity raises new challenges, akin to those face in realistic diagnostic applications. Here, we demonstrate the feasibility of inter-site classification of neuropsychiatric status, with an application to the Autism Brain Imaging Data Exchange (ABIDE) database, a large (N=871) multi-site autism dataset. For this purpose, we investigate pipelines that extract the most predictive biomarkers from the data. These R-fMRI pipelines build participant-specific connectomes from functionally-defined brain areas. Connectomes are then compared across participants to learn patterns of connectivity that differentiate typical controls from individuals with autism. We predict this neuropsychiatric status for participants from the same acquisition sites or different, unseen, ones. Good choices of methods for the various steps of the pipeline lead to 67% prediction accuracy on the full ABIDE data, which is significantly better than previously reported results. We perform extensive validation on multiple subsets of the data defined by different inclusion criteria. These enables detailed analysis of the factors contributing to successful connectome-based prediction. First, prediction accuracy improves as we include more subjects, up to the maximum amount of subjects available. Second, the definition of functional brain areas is of paramount importance for biomarker discovery: brain areas extracted from large R-fMRI datasets outperform reference atlases in the classification tasks.
Year
DOI
Venue
2017
10.1016/j.neuroimage.2016.10.045
NeuroImage
Keywords
Field
DocType
Data heterogeneity,Resting-state fMRI,Data pipelines,Biomarkers,Connectome,Autism spectrum disorders
Autism,Data mining,Functional magnetic resonance imaging,Connectome,Resting state fMRI,Psychology,Biomarker (medicine),Biomarker discovery,Autism brain imaging data exchange,Sample size determination
Journal
Volume
ISSN
Citations 
147
1053-8119
48
PageRank 
References 
Authors
2.04
24
7
Name
Order
Citations
PageRank
Alexandre Abraham11928.41
Michael P Milham288448.19
Adriana Di Martino343318.80
R. Cameron Craddock443419.21
Dimitris Samaras51740101.49
Bertrand Thirion65047270.40
Gael Varoquaux75309285.24