Towards Reproducible Brain-Wide Association Studies
By
Scott Marek,
Brenden Tervo-Clemmens,
Finnegan J. Calabro,
David F. Montez,
Benjamin P. Kay,
Alexander S. Hatoum,
Meghan Rose Donohue,
William Foran,
Ryland L. Miller,
Eric Feczko,
Oscar Miranda Dominguez,
Alice Graham,
Eric A. Earl,
Anders Perrone,
Michaela Cordova,
Olivia Doyle,
Lucille A. Moore,
Greg Conan,
Johnny Uriarte,
Kathy Snider,
Angela Tam,
Jianzhong Chen,
Dillan J. Newbold,
Annie Zheng,
Nicole A. Seider,
Andrew N. Van,
Timothy O. Laumann,
Wesley K Thompson,
Deanna J. Greene,
Steven E. Petersen,
Thomas Nichols,
Thomas B. T. Yeo,
Deanna M. Barch,
Hugh Garavan,
Beatriz Luna,
Damien A. Fair,
Nico UF Dosenbach
Posted 22 Aug 2020
bioRxiv DOI: 10.1101/2020.08.21.257758
Magnetic resonance imaging (MRI) continues to drive many important neuroscientific advances. However, progress in uncovering reproducible associations between individual differences in brain structure/function and behavioral phenotypes (e.g., cognition, mental health) may have been undermined by typical neuroimaging sample sizes (median N=25)1,2. Leveraging the Adolescent Brain Cognitive Development (ABCD) Study3 (N=11,878), we estimated the effect sizes and reproducibility of these brain wide associations studies (BWAS) as a function of sample size. The very largest, replicable brain wide associations for univariate and multivariate methods were r=0.14 and r=0.34, respectively. In smaller samples, typical for brain wide association studies, irreproducible, inflated effect sizes were ubiquitous, no matter the method (univariate, multivariate). Until sample sizes started to approach consortium levels, BWAS were underpowered and statistical errors assured. Multiple factors contribute to replication failures4,5,6; here, we show that the pairing of small brain behavioral phenotype effect sizes with sampling variability is a key element in widespread BWAS replication failure. Brain behavioral phenotype associations stabilize and become more reproducible with sample sizes of N>2,000. While investigator initiated brain behavior research continues to generate hypotheses and propel innovation, large consortia are needed to usher in a new era of reproducible human brain wide association studies. ### Competing Interest Statement Nico Dosenbach and Damien Fair are co-founders of Nous Imaging
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