Functional Connectome of the Fetal Brain

Abstract

Large-scale functional connectome formation and reorganization is apparent in the second trimester of pregnancy, making it a crucial and vulnerable time window in connectome development. Here we identified which architectural principles of functional connectome organization are initiated before birth, and contrast those with topological characteristics observed in the mature adult brain. A sample of 105 pregnant women participated in human fetal resting-state fMRI studies (fetal gestational age between 20 and 40 weeks). Connectome analysis was used to analyze weighted network characteristics of fetal macroscale brain wiring. We identified efficient network attributes, common functional modules, and high overlap between the fetal and adult brain network. Our results indicate that key features of the functional connectome are present in the second and third trimesters of pregnancy. Understanding the organizational principles of fetal connectome organization may bring opportunities to develop markers for early detection of alterations of brain function.SIGNIFICANCE STATEMENT The fetal to neonatal period is well known as a critical stage in brain development. Rapid neurodevelopmental processes establish key functional neural circuits of the human brain. Prenatal risk factors may interfere with early trajectories of connectome formation and thereby shape future health outcomes. Recent advances in MRI have made it possible to examine fetal brain functional connectivity. In this study, we evaluate the network topography of normative functional network development during connectome genesis in utero Understanding the developmental trajectory of brain connectivity provides a basis for understanding how the prenatal period shapes future brain function and disease dysfunction.

Keywords: brain development; fetal; functional connectivity; prenatal; resting-state fMRI.

Figure 1.

Fetal functional connectome reconstruction. A total of 105 healthy pregnant women underwent MRI examination of the fetal brain, including T2 and fMRI sequences (top left T2 image, courtesy of Wilhelmina Children's Hospital, Utrecht, the Netherlands). Preprocessed resting state fMRI images of 105 fetuses were parcellated using a manually annotated Desikan–Killiany atlas. Subject-level time series from all voxels within a region were averaged and correlated to all other regions of the atlas. This resulted into a FC matrix of 66 cortical nodes, preserving only positive associations (correlation coefficient between 0 and 1) in this visual representation.

Figure 2.

Connectomic features of the fetal group matrix. a, Modular organization plotted on the fetal cortex with colors representing composition of four modules observed in fetal brain function. b, The rich-club regions in red plotted on the fetal cortex. Right, The rich-club curve (in red) is displayed with a significant rich-club organization for the range of 22 ≤ k ≤ 38 [ϕ_norm^w(k) > 1], strongly suggesting the existence of a densely interconnected network of central hubs in the fetal connectome (van den Heuvel and Sporns, 2011).

Figure 3.

Comparison of group averaged fetal and adult functional connectome modules. Illustration of the modular organization modules of the fetal (left) and adult (right) connectivity matrices. Blue dots represent positive correlations between nodes; the upper 10% of the highest connections are shown. Both matrices display the adult modular organization, revealing a temporal, default-mode, visual, frontomedial, and motor network.