Rich-club organization of the newborn human brain

Abstract

Combining diffusion magnetic resonance imaging and network analysis in the adult human brain has identified a set of highly connected cortical hubs that form a "rich club"-a high-cost, highcapacity backbone thought to enable efficient network communication. Rich-club architecture appears to be a persistent feature of the mature mammalian brain, but it is not known when this structure emerges during human development. In this longitudinal study we chart the emergence of structural organization in mid to late gestation. We demonstrate that a rich club of interconnected cortical hubs is already present by 30 wk gestation. Subsequently, until the time of normal birth, the principal development is a proliferation of connections between core hubs and the rest of the brain. We also consider the impact of environmental factors on early network development, and compare term-born neonates to preterm infants at term-equivalent age. Though rich-club organization remains intact following premature birth, we reveal significant disruptions in both in cortical-subcortical connectivity and short-distance corticocortical connections. Rich club organization is present well before the normal time of birth and may provide the fundamental structural architecture for the subsequent emergence of complex neurological functions. Premature exposure to the extrauterine environment is associated with altered network architecture and reduced network capacity, which may in part account for the high prevalence of cognitive problems in preterm infants.connectome | brain development | tractography | preterm birth T o understand the functional properties of a complex network it is necessary to examine its structural organization and topological properties. In the human brain this can be achieved at a macroscale by tracing white matter connections between brain regions with diffusion MRI; this enables the interrogation of structural network topology in vivo with millimeter-scale spatial resolution, providing complementary evidence to experimental studies (1, 2).Network analysis of the adult human structural connectome has revealed a set of highly connected cortical "hubs" predominantly located in heteromodal association cortex, that provide a foundation for coherent neuronal activation across distal cortical regions (3-5). Further, some hub regions tend to be densely connected to each other, forming a "rich club" comprised of frontal and parietal cortex, precuneus, cingulate and the insula, as well as the hippocampus, thalamus, and putamen (6). Rich-club organization has been identified in a number of complex networks (7) and represents an attractive feature for investigation in the brain because rich-club connections tend to dominate network topology (8). Rich-club architecture appears to be a fundamental feature of the mature mammalian brain with similar organization identified in animal models (9, 10).It has been suggested that the emergence of complex neurological function is associated with the integration of major hubs across the cortex (11,...

Specialization and integration of functional thalamocortical connectivity in the human infant

“…We show for the first time, to our knowledge, that, already by the time of normal birth, the topographical organization of functional thalamocortical connectivity defined by strongest connectivity is consistent with current information on the adult brain using tracer methods (25)(26)(27)(28)(29)(30), diffusion studies (15,16), and functional imaging in adult subjects (18). These results add to the growing evidence of the maturity of the human brain by the time of normal birth (12,31,32).…”

A transcriptional signature of hub connectivity in the mouse connectome

“…Although many aspects of gene expression in the brain show a developmentally persistent profile (35), it is unclear whether the same transcriptional signature of hub connectivity would be apparent throughout development. Although rich club connectivity seems to be established early in development (2,36), it also undergoes significant remodeling later in life (37). Interestingly, recent evidence indicates that aerobic glycolysis plays a prominent role in biosynthesis and growth and that it accounts for a larger fraction of the brain's energetic needs earlier in development, peaking in early childhood when levels of synaptic development are highest (35).…”

Structural network analysis of brain development in young preterm neonates

“…The structural connectomes defined in the previous section are networks and it has become popular to examine these networks using various network measures [2,32,40,44,47,58]. The collection of network measures used here are given in Table 2.…”

“…Tymofiyeva et al used an atlas-free approach to analyze connectome development in preterm infants, children and adults, also employing network measures to capture topological changes [52,53]. Very recently, Ball et al studied a specific network measure known as rich-club organization in a cohort of preterm infants [2]. They found that this rich-club structure, known to be present in adult brain networks, emerges as early as 30 weeks PMA.…”