On the brain structure heterogeneity of autism: Parsing out acquisition site effects with significance-weighted principal component analysis

Francisco Jesús Martinez-Murcia, Meng Chuan Lai, Juan Manuel Górriz*, Javier Ramírez, Adam M H Young, Sean C L Deoni, Christine Ecker, Michael V. Lombardo, Simon Baron-Cohen, Declan G M Murphy, Edward T. Bullmore, John Suckling, Anthony J. Bailey, Simon Baron-Cohen, Patrick F. Bolton, Edward T. Bullmore, Sarah Carrington, Marco Catani, Bhismadev Chakrabarti, Michael C. CraigEileen M. Daly, Sean C L Deoni, Christine Ecker, Francesca Happé, Julian Henty, Peter Jezzard, Patrick Johnston, Derek K. Jones, Meng Chuan Lai, Michael V. Lombardo, Anya Madden, Diane Mullins, Clodagh M. Murphy, Declan G M Murphy, Greg Pasco, Amber N V Ruigrok, Susan A. Sadek, Debbie Spain, Rose Stewart, John Suckling, Sally J. Wheelwright, Steven C. Williams

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)
257 Downloads (Pure)


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.

Original languageEnglish
Pages (from-to)1208-1223
Number of pages16
JournalHuman Brain Mapping
Issue number3
Early online date24 Oct 2016
Publication statusPublished - 1 Mar 2017


  • autism spectrum disorder
  • structural heterogeneity
  • structural magnetic resonance imaging
  • voxel based morphometry


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