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Periventricular white matter injury is common in very preterm infants and it is associated with long term neurodevelopmental impairments. While evidence supports the protective effects of erythropoetin (EPO) in preventing injury, we currently lack the complete understanding of how EPO affects the emergence and maturation of anatomical brain connectivity and function. In this case-control study, connectomic analysis based on diffusion MRI tractography was applied to evaluate the effect of early high-dose EPO in preterm infants. A whole brain, network-level analysis revealed a sub-network of anatomical brain connections in which connectivity strengths were significantly stronger in the EPO group. This distributed network comprised connections predominantly in the frontal and temporal lobe bilaterally, and the effect of EPO was focused on peripheral and feeder connections of the core structural connectivity network. EPO resulted in a globally increased clustering coefficient, higher global and average local efficiency, while higher strength and increased clustering was found for regions in the frontal lobe and cingulate gyrus. The connectivity network most affected by the EPO treatment showed a steeper increase graph theoretical measures with age compared to the placebo group. Our results demonstrate a weak but widespread effect of EPO on the structural connectivity network and a possible trophic effect of EPO reflected by increasing network segregation, predominantly in local connections., Highlights • Erythropoietin (EPO) is a potential neuroprotective agent in very preterm infants. • EPO leads to increased structural brain connectivity in fronto-temporal regions. • Clustering coefficient, local and global efficiency increases after EPO treatment.

Brain function is tightly linked to the development of the cortex. Until recently, assessing the human cortical development and folding was not possible in vivo. It is magnetic resonance imaging and new post-processing image analysis tools that have improved the understanding of cortical development. The combination of conventional magnetic resonance imaging and diffusion tensor imaging has further allowed depiction of the relationship of changes in intracortical layering and cortical folding. Being able to follow these early developmental processes has elucidated changes in early brain development due to changed environmental conditions in fetal life such as twinning and fetal growth restriction and postnatal conditions such as prematurity. This review further illustrates new data on brain structural asymmetries linked to the emergence of early language functions.

Within preterm-born children, being born male and at a lower gestational age (GA) have both been associated with a heightened risk for developmental difficulties. However, in this population little is known about the combined effect and the influence of these risk factors on cortical structures and executive control. In the present study, 58 preterm-born children (GA ranging from 24.0 to 35.1 weeks) were administered the computerized Child Attention Network Task at 6 years of age. Brain magnetic resonance imaging was performed and analyzed using Voxel-Based Morphometry (VBM) in all children. At a behavioral level, boys born28 weeks of GA had significantly less executive control than preterm-born girls28 weeks (p = .001) and preterm-born boys ≥28 (p = .003). The reduced executive control in preterm-born boys28 weeks gestation was related to lower cortical densities in the inferior frontal gyrus (IFG) and dorsolateral prefrontal cortex (DLPFC). The current study links the higher incidence of reduced executive control in preterm-born boys to a higher degree of prematurity (low GA) and identifies brain structural abnormalities in the prefrontal cortex related to these deficits. The implications of these results are discussed.

International audience; In this article we propose to investigate the analogy between early cortical folding process and cortical smoothing by mean curvature flow. First, we introduce a one-parameter model that is able to fit a developmental trajectory as represented in a Volume-Area plot and we propose an efficient optimization strategy for parameter estimation. Second, we validate the model on forty cortical surfaces of preterm newborns by comparing global geometrical indices and trajectories of central sulcus along developmental and simulation time.

Understanding human brain development from the fetal life to adulthood is of great clinical importance as many neurological and neurobehavioral disorders have their origin in early structural and functional cerebral maturation. The developing brain is particularly prone to being affected by endogenous and exogenous events through the fetal and early postnatal life. The concept of 'developmental plasticity or disruption of the developmental program' summarizes these events. Increases in white matter, which speed up communication between brain cells, growing complexity of neuronal networks suggested by gray and white matter changes, and environmentally sensitive plasticity are all essential aspects in a child's ability to mentalize and maintain the adaptive flexibility necessary for achieving high sociocognitive functioning. Advancement in neuroimaging has opened up new ways for examining the developing human brain in vivo, the study of the effects of early antenatal, perinatal and neonatal events on later structural and functional brain development resulting in developmental disabilities or developmental resilience. In this review, methods of quantitative assessment of human brain development, such as 3D-MRI with image segmentation, diffusion tensor imaging to assess connectivity and functional MRI to visualize brain function will be presented.

Development of brain functions and the structural-functional correlates of brain injury remain difficult to evaluate in the young infant. Thus, new noninvasive methods capable of early functional diagnosis are needed. This review describes the use of functional magnetic resonance imaging (fMRI) for studying localization of brain function in the developing brain when standard clinical investigations are not available or conclusive. This promising neuroimaging technique has been successfully used in healthy newborns and in newborns with brain injury using different paradigms, including passive visual, somato-sensorial, and auditory stimulation. We summarize the major findings of previous fMRI studies in young infants, describe ongoing methodological challenges, and propose exciting future developments in using resting-state protocols and functional connectivity techniques to assist in evaluating early life brain function and its recovery from injury.

Understanding early human brain development is of great clinical importance, as many neurological and neurobehavioral disorders have their origin in early structural and functional cerebral organization and maturation. Diffusion tensor imaging (DTI), a recent magnetic resonance (MR) modality which assesses water diffusion in biological tissues at a microstructural level, has revealed a powerful technique to explore the structural basis of normal brain development. In fact, the tissue organization can be probed non-invasively, and the age-related changes of diffusion parameters (mean diffusivity, anisotropy) reveal crucial maturational processes, such as white matter myelination. Nevertheless, the developing human brain presents several challenges for DTI applications compared with the adult brain. DTI may further be used to detect brain injury well before conventional MRI, as water diffusion changes are an early indicator of cellular injury. This is particularly critical in infants in the context of administration of neuroprotective therapies. Changes in diffusion characteristics further provide early evidence of both focal and diffuse white matter injury in association with periventricular leukomalacia in the preterm infant. Finally, with the development of 3D fiber tractography, the maturation of white matter connectivity can be followed throughout infant development into adulthood with the potential to study correlations between abnormalities on DTI and ultimate neurologic/cognitive outcome.

The human brain is susceptible to a wide variety of insults. The permanent residua of these abnormalities are represented in dysfunction of one or more areas of neurodevelopment. A full understanding of normal brain development, mechanisms of brain injury, and consequences for subsequent brain development is required to determine which infants are at risk for neurodevelopmental handicap, and to monitor the effects of new treatments and management regimens designed to prevent these disabilities. Advanced magnetic resonance techniques, such as quantitative morphometric magnetic resonance techniques, diffusion-weighted magnetic resonance techniques, and magnetic resonance spectroscopy applied to the study of early human brain development have given us a better understanding of the pathophysiologic mechanisms of brain injury and its effects on subsequent brain development. Magnetic resonance imaging has provided an invaluable tool for the study of the fetal and newborn brain in vivo.