Functional covariance modes reveal aligned fetal and neonatal brain functional connectomes.

Abstract

Spatially distributed functional networks are a fundamental property of brain organisation. While these networks are already present at full-term birth, establishing whether they exist before birth remains problematic, given the challenges inherent to in utero fMRI. Here, we introduce a seed-based functional covariance modes (FCMs) approach, which leverages inter-subject variability in connectivity between distinct regions and the rest of the brain to infer whole-brain network configurations. Unlike standard group-level independent component analysis, which consistently fails to reveal spatially distributed neural networks in fetal populations, FCMs successfully delineated a range of brain-wide functional networks in utero with high spatial fidelity to neonatal network maps, including bilateral organisation - a landmark feature of many neonatal functional networks. Furthermore, we demonstrated that bilateral fetal networks preferentially clustered along the brain midline and around cortical limbic territories. In contrast, single-hemisphere dominant networks mapped into areas associated with hemispheric functional asymmetry in the mature brain, including the highly lateralised language circuits. Together, these findings provide coherent evidence that the blueprint for the functional brain architecture, including its functional specialisation, is formed before birth.