Hierarchical Complexity of the Macro-Scale Neonatal Brain

Abstract

The human adult structural connectome has a rich nodal hierarchy, with highly diverse connectivity patterns aligned to the diverse range of functional specializations in the brain. The emergence of this hierarchical complexity in human development is unknown. Here, we substantiate the hierarchical tiers and hierarchical complexity of brain networks in the newborn period, assess correspondences with hierarchical complexity in adulthood, and investigate the effect of preterm birth, a leading cause of atypical brain development and later neurocognitive impairment, on hierarchical complexity. We report that neonatal and adult structural connectomes are both composed of distinct hierarchical tiers and that hierarchical complexity is greater in term born neonates than in preterms. This is due to diversity of connectivity patterns of regions within the intermediate tiers, which consist of regions that underlie sensorimotor processing and its integration with cognitive information. For neonates and adults, the highest tier (hub regions) is ordered, rather than complex, with more homogeneous connectivity patterns in structural hubs. This suggests that the brain develops first a more rigid structure in hub regions allowing for the development of greater and more diverse functional specialization in lower level regions, while connectivity underpinning this diversity is dysmature in infants born preterm.

Keywords: dMRI; developing brain; hierarchical complexity; network analysis; newborn; structural connectome.

Figure 1

An example of the parcellation and the segmentation from three different subjects: a) a preterm born baby, b) a term born baby, and c) an adult subject. From left to right, the parcellation and the four different tissue probability maps included in the five tissue type file: gray matter, subcortical gray matter, white matter, and cerebrospinal fluid. For the neonates, the maps are overlaid onto the T2w volumes for the neonates and onto the T1w volume for the adult.

Figure 2

Illustration of ordered and complex hierarchical networks. Tiers are determined by the degree of nodes, with nodes with the largest degrees in the top tier. Tier 2 nodes and links are highlighted. In an ordered hierarchy, all nodes of similar degree are connected in a similar fashion, while a complex hierarchy is characterized by heterogeneous connectivity patterns across similar degree nodes.

Figure 3

Aggregated degree distributions of neonatal groups, top, and the adult group, bottom. Four distinct peaks are noted in the degree distributions of neonatal connectomes and corresponding peaks are also seen in the adult connectomes. The four Gaussian Mixture Model components are shown as C4, C3, C2, and C1. These are taken as the natural tiers of the connectomes and black dotted lines indicate the thresholds between tiers. Greater consistency between neonates and adults is found by consolidating the tiers as indicated by Tier A, B, and C.

Figure 4

Cortical and sub-cortical representations colored by tier. N/A means non assigned. Due to the display plane used, two areas are not shown, the accumbens area, which was assigned (in both hemispheres) to Tier 4 in all three populations; and the cerebellum, which was assigned (in both hemispheres) to Tier 3 in all three populations.

Figure 5

Distribution of the global hierarchical complexity () for the three populations as rain cloud plots (top) and hierarchical complexity of the three tiers in neonatal populations (bottom). Wilcoxon rank sum -values and Cohen’s values are shown for preterm versus term (all) and term versus adult (top). *Denotes significant difference after FDR correction.

Figure 6

Distributions of hierarchical complexity globally (top) and for the different tiers of the three populations. Grey, yellow, and orange colors represent values for adults, term born, and preterm born neonates, respectively, while blue represents the values of hierarchical complexity for their corresponding configuration models. Wilcoxon rank sum -values and Cohen’s values are shown in top right corner of each plot. Axes as in top left plot. *Denotes significant difference after FDR correction.