title: On the brain structure heterogeneity of autism: Parsing out acquisition site effects with significance-weighted principal component analysis.
abstract: Neuroimaging studies have reported structural and physiological differences that could help understand the causes and development of Autism Spectrum Disorder (ASD). Many of them rely on multisite designs, with the recruitment of larger samples increasing statistical power. However, recent large-scale studies have put some findings into question, considering the results to be strongly dependent on the database used, and demonstrating the substantial heterogeneity within this clinically defined category. One major source of variance may be the acquisition of the data in multiple centres. In this work we analysed the differences found in the multisite, multi-modal neuroimaging database from the UK Medical Research Council Autism Imaging Multicentre Study (MRC AIMS) in terms of both diagnosis and acquisition sites. Since the dissimilarities between sites were higher than between diagnostic groups, we developed a technique called Significance Weighted Principal Component Analysis (SWPCA) to reduce the undesired intensity variance due to acquisition site and to increase the statistical power in detecting group differences. After eliminating site-related variance, statistically significant group differences were found, including Broca's area and the temporo-parietal junction. However, discriminative power was not sufficient to classify diagnostic groups, yielding accuracies results close to random. Our work supports recent claims that ASD is a highly heterogeneous condition that is difficult to globally characterize by neuroimaging, and therefore different (and more homogenous) subgroups should be defined to obtain a deeper understanding of ASD. Hum Brain Mapp 38:1208-1223, 2017. © 2016 Wiley Periodicals, Inc.
authors: Department of Signal Theory Networking and Communications, C/Periodista Daniel Saucedo Aranda S/N, E-18071, University of Granada, Granada, Spain.
authors: Francisco Jesús
authors: 0000-0001-8146-7056
authors: FJ
authors: Martinez-Murcia
authors: Child and Youth Mental Health Collaborative at The Centre for Addiction and Mental Health and The Hospital for Sick Children, Toronto, Ontario, Canada.|Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.|Department of Psychiatry, Autism Research Centre, University of Cambridge, Cambridge, United Kingdom.|Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors: Meng-Chuan
authors: MC
authors: Lai
authors: Department of Signal Theory Networking and Communications, C/Periodista Daniel Saucedo Aranda S/N, E-18071, University of Granada, Granada, Spain.
authors: Juan Manuel
authors: JM
authors: Górriz
authors: Department of Signal Theory Networking and Communications, C/Periodista Daniel Saucedo Aranda S/N, E-18071, University of Granada, Granada, Spain.
authors: Javier
authors: J
authors: Ramírez
authors: Department of Psychiatry, Autism Research Centre, University of Cambridge, Cambridge, United Kingdom.
authors: Adam M H
authors: AM
authors: Young
authors: Advanced Baby Imaging Laboratory, School of Engineering, Brown University, Providence, Rhode Island.
authors: Sean C L
authors: SC
authors: Deoni
authors: Department of Forensic and Neurodevelopmental Sciences, Sackler Institute for Translational Neurodevelopment, London, United Kingdom.|Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
authors: Christine
authors: C
authors: Ecker
authors: Department of Psychiatry, Autism Research Centre, University of Cambridge, Cambridge, United Kingdom.|Department of Psychology and Center for Applied Neuroscience, University of Cyprus, Nicosia, Cyprus.
authors: Michael V
authors: MV
authors: Lombardo
authors: Department of Psychiatry, Autism Research Centre, University of Cambridge, Cambridge, United Kingdom.|Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, United Kingdom.
authors: Simon
authors: S
authors: Baron-Cohen
authors: Department of Forensic and Neurodevelopmental Sciences, Sackler Institute for Translational Neurodevelopment, London, United Kingdom.|Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
authors: Declan G M
authors: DG
authors: Murphy
authors: Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, United Kingdom.|Department of Psychiatry, Brain Mapping Unit, University of Cambridge, Cambridge, United Kingdom.
authors: Edward T
authors: ET
authors: Bullmore
authors: Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, United Kingdom.|Department of Psychiatry, Brain Mapping Unit, University of Cambridge, Cambridge, United Kingdom.
authors: John
authors: J
authors: Suckling
mesh_terms: D000293:Adolescent; D000328:Adult; D001321:Autistic Disorder / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D001931:Brain Mapping; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D025341:Principal Component Analysis; D055815:Young Adult
keywords: autism spectrum disorder; structural heterogeneity; structural magnetic resonance imaging; voxel based morphometry