Dynamical consequences of regional heterogeneity in the brain’s transcriptional landscape

Deco, Gustavo; Kringelbach, Morten L.; Arnatkeviciute, Aurina; Oldham, Stuart; Sabaroedin, Kristina; Rogasch, Nigel C.; Aquino, Kevin; Fornito, Alex

doi:http://doi.org/10.1126/sciadv.abf4752

Dynamical consequences of regional heterogeneity in the brain’s transcriptional landscape

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Deco G, Kringelbach ML, Arnatkeviciute A, Oldham S,Sabaroedin K, Rogasch NC, Aquino KM, Fornito A. Dynamical consequences of regional heterogeneity in the brain’s transcriptional landscape. Sci Adv. 2021;7(29):eabf4752. DOI: 10.1126/sciadv.abf4752

Abstract

Brain regions vary in their molecular and cellular composition, but how this heterogeneity shapes neuronal dynamics is unclear. Here, we investigate the dynamical consequences of regional heterogeneity using a biophysical model of whole-brain functional magnetic resonance imaging (MRI) dynamics in humans. We show that models in which transcriptional variations in excitatory and inhibitory receptor (E:I) gene expression constrain regional heterogeneity more accurately reproduce the spatiotemporal structure of empirical functional connectivity estimates than do models constrained by global gene expression profiles or MRI-derived estimates of myeloarchitecture. We further show that regional transcriptional heterogeneity is essential for yielding both ignition-like dynamics, which are thought to support conscious processing, and a wide variance of regional-activity time scales, which supports a broad dynamical range. We thus identify a key role for E:I heterogeneity in generating complex neuronal dynamics and demonstrate the viability of using transcriptomic data to constrain models of large-scale brain function.