Correlated gene expression supports synchronous activity 2 in brain networks

12 A recent report claims that functional brain networks defined with resting-state functional 13 magnetic resonance imaging (fMRI) can be recapitulated with correlated gene expression (i.e. 14 high within-network tissue-tissue " strength fraction " , SF) (Richiardi et al., 2015). However, the 15 authors do not adequately control for spatial proximity. We replicated their main analysis, 16 performed a more effective adjustment for spatial proximity, and tested whether " null networks " 17 (i.e. clusters with center coordinates randomly placed throughout cortex) also exhibit high SF. 18 Removing proximal tissue-tissue correlations by Euclidean distance, as opposed to removing 19 correlations within arbitrary tissue labels as in (Richiardi et al., 2015), reduces within-network 20 SF to no greater than null. Moreover, randomly placed clusters also have significantly high SF, 21 indicating that high within-network SF is entirely attributable to proximity and is unrelated to 22 functional brain networks defined by resting-state fMRI. We discuss why additional validations 23 in the original article are invalid and/or misleading and suggest future directions. A recent study explores relationships between gene expression and distributed spatial 27 patterns of synchronous brain activity consistently observed in resting state (RS) fMRI (Richiardi 28 et al., 2015) using microarray data from the Allen Brain Atlas (http://human.brain-map.org, 29. CC-BY 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not .