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Abstract
A pivotal question in modern neuroscience is which genes regulate brain circuits that underlie cognitive functions. However, the field is still in its infancy. Here we report an integrated investigation of the high-level language network (i.e., sentence-processing network) in the human cerebral cortex, combining regional gene expression profiles, task fMRI, large-scale neuroimaging meta-analysis, and resting-state functional network approaches. We revealed reliable gene expression-functional network correlations using three different network definition strategies, and identified a consensus set of genes related to connectivity within the sentence-processing network. The genes involved showed enrichment for neural development and actin-related functions, as well as association signals with autism, which can involve disrupted language functioning. Our findings help elucidate the molecular basis of the brain's infrastructure for language. The integrative approach described here will be useful for studying other complex cognitive traits.
Highlights
A pivotal question in modern neuroscience is which genes regulate brain circuits that underlie cognitive functions
Given the absence of a universally agreed upon protocol for localizing brain regions that support high-level language processing (Fedorenko & Thompson-Schill, 2014), we used three different definition strategies: (1) Supramodal Sentence Areas based on the concordance of activation across three language fMRI tasks and leftward lateralization completed by 144 healthy right-handers (Labache et al, 2018), (2) Synthesized Sentence Areas based on large-scale neuroimaging meta-analysis of fMRI studies (Yarkoni et al, 2011), and (3) One-contrast Sentence Areas based on the probabilistic activation map of a single language-task fMRI contrast (Fedorenko et al, 2010)
Regions were defined according to the Atlas of Intrinsic Connectivity of Homotopic Areas (AICHA) brain atlas, which is derived from resting-state functional MRI (rs-fMRI) connectivity data, with each region showing homogeneity of functional temporal activity within itself (Joliot et al, 2015)
Summary
A pivotal question in modern neuroscience is which genes regulate brain circuits that underlie cognitive functions. 2018; Romme, de Reus, Ophoff, Kahn, & van den Heuvel, 2017; Vertes et al, 2016) This approach has brought important new advances: Transcriptional profiles have been linked to neural architecture with respect to both functional connectivity measured during the resting state ( called intrinsic connectivity) (Richiardi et al, 2015; Vertes et al, 2016) and structural connectivity (Fulcher & Fornito, 2016; Richiardi et al, 2015), as well as to alterations of connectivity in brain disorders such as schizophrenia (Romme et al, 2017), autism spectrum disorder (ASD; Romero-Garcia et al, 2018), and Huntington’s disease (McColgan et al, 2018). A necessary assumption is that the group-averaged gene expression map, within a given postmortem data set, is sufficiently representative to be matched with the group-averaged neuroimaging-derived map from a set of living subjects
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