The functions of the resting state networks (RSNs) revealed by functional MRI remain unclear, but it has seemed possible that networks emerge in parallel with the development of related cognitive functions. We tested the alternative hypothesis: that the full repertoire of resting state dynamics emerges during the period of rapid neural growth before the normal time of birth at term (around 40 wk of gestation). We used a series of independent analytical techniques to map in detail the development of different networks in 70 infants born between 29 and 43 wk of postmenstrual age (PMA). We characterized and charted the development of RSNs from recognizable but often fragmentary elements at 30 wk of PMA to full facsimiles of adult patterns at term. Visual, auditory, somatosensory, motor, default mode, frontoparietal, and executive control networks developed at different rates; however, by term, complete networks were present, several of which were integrated with thalamic activity. These results place the emergence of RSNs largely during the period of rapid neural growth in the third trimester of gestation, suggesting that they are formed before the acquisition of cognitive competencies in later childhood.blood oxygen level-dependent | functional MRI | neurodevelopment | intrinsic brain activity | newborn T he detection of spontaneous spatially coherent fluctuations of the blood oxygen level-dependent (BOLD) signal by functional MRI (fMRI) (1) offers potential insights into the largescale organization of neural function at the system levels (comprehensive review presented in 2). These resting state networks (RSNs) replicate the set of functional networks exhibited by the brain over its range of possible tasks (3), encompassing various spatially distinct neural systems, including the medial visual and lateral visual, auditory, somatosensory, motor, cerebellum, executive control, and frontoparietal or dorsal visual stream networks as well as the default mode network (DMN) (2-4). However, although the configurations and consistency of these networks are established, their functions are still not fully understood.Elucidating the ontogeny of RSNs could clarify the role of this large-scale neural organization. Previous studies at the time of normal birth [term, around 40 wk of postmenstrual age (PMA)] have detected RSNs in the primary visual areas, somatosensory and motor cortices, temporal cortex, cerebellum, prefrontal cortex (5, 6), and incomplete DMN (7) but did not find the complete DMN, executive control network, or dorsal visual network. This led to the suggestion that the full architecture emerges during later childhood in parallel with the development of corresponding cognitive functions.Here, we test the alternative hypothesis: that the full adult repertoire of resting state dynamics emerges during the period of rapid neural growth before the normal time of birth at 38-43 postconceptional weeks (term).We used a series of independent analytical techniques to map in detail the development of different networks in ...

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,...

Preterm birth is a leading cause of cognitive impairment in childhood and is associated with cerebral gray and white matter abnormalities. Using multimodal image analysis, we tested the hypothesis that altered thalamic development is an important component of preterm brain injury and is associated with other macro- and microstructural alterations. T1- and T2-weighted magnetic resonance images and 15-direction diffusion tensor images were acquired from 71 preterm infants at term-equivalent age. Deformation-based morphometry, Tract-Based Spatial Statistics, and tissue segmentation were combined for a nonsubjective whole-brain survey of the effect of prematurity on regional tissue volume and microstructure. Increasing prematurity was related to volume reduction in the thalamus, hippocampus, orbitofrontal lobe, posterior cingulate cortex, and centrum semiovale. After controlling for prematurity, reduced thalamic volume predicted: lower cortical volume; decreased volume in frontal and temporal lobes, including hippocampus, and to a lesser extent, parietal and occipital lobes; and reduced fractional anisotropy in the corticospinal tracts and corpus callosum. In the thalamus, reduced volume was associated with increased diffusivity. This demonstrates a significant effect of prematurity on thalamic development that is related to abnormalities in allied brain structures. This suggests that preterm delivery disrupts specific aspects of cerebral development, such as the thalamocortical system.