A Machine Learning Approach to Reveal the NeuroPhenotypes of Autisms
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AuthorGorriz Sáez, Juan Manuel; Ramírez Pérez De Inestrosa, Javier; Segovia Román, Fermín; Segovia Román, Fermín; Martínez Murcia, Francisco Jesús
World Scientific Publishing
MRIMulticlass classificationUpper boundsAutismSpatial overlap analysis
J. M. Górriz et al. International Journal of Neural Systems, Vol. 29, No. 7 (2019) 1850058 [DOI: 10.1142/S0129065718500582]
SponsorshipThis work was partly supported by the MINECO Under the TEC2015-64718-R Project, the Salvador de Madariaga Mobility Grants 2017 and the Consejería de Economía, Innovación, Ciencia y Empleo (Junta de Andalucía, Spain) under the Excellence Project P11-TIC-7103; The Project was supported by the UK Medical Research Council (Grant No. GO 400061) and European Autism Interventions — a Multicentre Study for Developing New Medications (EU-AIMS); EU-AIMS has received support from the Innovative Medicines Initiative Joint Undertaking Under Grant Agreement No. 115300; MVL was supported by the British Academy, Jesus College Cambridge, Wellcome Trust, and an ERC Starting Grant (ERC-2017-STG; 755816)
Although much research has been undertaken, the spatial patterns, developmental course, and sexual dimorphism of brain structure associated with autism remains enigmatic. One of the difficulties in investigating differences between the sexes in autism is the small sample sizes of available imaging datasets with mixed sex. Thus, the majority of the investigations have involved male samples, with females somewhat overlooked. This paper deploys machine learning on partial least squares feature extraction to reveal differences in regional brain structure between individuals with autism and typically developing participants. A four-class classification problem (sex and condition) is specified, with theoretical restrictions based on the evaluation of a novel upper bound in the resubstitution estimate. These conditions were imposed on the classifier complexity and feature space dimension to assure generalizable results from the training set to test samples. Accuracies above 80% on gray and white matter tissues estimated from voxel-based morphometry (VBM) features are obtained in a sample of equal-sized high-functioning male and female adults with and without autism (N=120, n=30/group). The proposed learning machine revealed how autism is modulated by biological sex using a low-dimensional feature space extracted from VBM. In addition, a spatial overlap analysis on reference maps partially corroborated predictions of the “extreme male brain” theory of autism, in sexual dimorphic areas.