Adjusting for allometric scaling in ABIDE I challenges subcortical volume differences in autism spectrum disorder

Abstract

Inconsistencies across studies investigating subcortical correlates of autism spectrum disorder (ASD) may stem from small sample size, sample heterogeneity, and omitting or linearly adjusting for total brain volume (TBV). To properly adjust for TBV, brain allometry—the nonlinear scaling relationship between regional volumes and TBV—was considered when examining subcortical volumetric differences between typically developing (TD) and ASD individuals. Autism Brain Imaging Data Exchange I (ABIDE I; N = 654) data was analyzed with two methodological approaches: univariate linear mixed effects models and multivariate multiple group confirmatory factor analyses. Analyses were conducted on the entire sample and in subsamples based on age, sex, and full scale intelligence quotient (FSIQ). A similar ABIDE I study was replicated and the impact of different TBV adjustments on neuroanatomical group differences was investigated. No robust subcortical allometric or volumetric group differences were observed in the entire sample across methods. Exploratory analyses suggested that allometric scaling and volume group differences may exist in certain subgroups defined by age, sex, and/or FSIQ. The type of TBV adjustment influenced some reported volumetric and scaling group differences. This study supports the absence of robust volumetric differences between ASD and TD individuals in the investigated volumes when adjusting for brain allometry, expands the literature by finding no group difference in allometric scaling, and further suggests that differing TBV adjustments contribute to the variability of reported neuroanatomical differences in ASD.

Abstract

To properly adjust for TBV, brain allometry—the nonlinear scaling relationship between regional volumes and TBV—was considered when examining subcortical volumetric differences between typically developing and ASD individuals. No robust subcortical allometric or volumetric group differences were observed in the entire sample across the univariate linear mixed effects models and the multivariate multiple group confirmatory factor analyses.