Rich-club organization of the newborn human brain

Significance To investigate the organizational principles of human brain development, we analyzed cerebral structural connectivity in the period leading up to the time of normal birth. We found that a “rich club” of interconnected cortical hubs previously reported in adults is present by 30 wk gestation. From mid to late gestation, connections between core hubs and the rest of the brain increased significantly. To determine the influence of environmental factors on network development, we also compared term-born infants to those born prematurely. Alterations in cortical–subcortical connectivity and short-distance connections outside the core network were associated with prematurity. Rich-club organization in the human brain precedes the emergence of complex neurological function, and alterations during this time may impact negatively on subsequent neurodevelopment. 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, high-capacity 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.

[1]  Daniel Rueckert,et al.  The influence of preterm birth on the developing thalamocortical connectome , 2013, Cortex.

[2]  Serena J. Counsell,et al.  Diffusion magnetic resonance imaging in preterm brain injury , 2013, Neuroradiology.

[3]  J. Neil,et al.  Neonatal intensive care unit stress is associated with brain development in preterm infants , 2011, Annals of neurology.

[4]  H E Stanley,et al.  Classes of small-world networks. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Kaustubh Supekar,et al.  Reconceptualizing functional brain connectivity in autism from a developmental perspective , 2013, Front. Hum. Neurosci..

[6]  Daniel Rueckert,et al.  Nonrigid registration using free-form deformations: application to breast MR images , 1999, IEEE Transactions on Medical Imaging.

[7]  Alan Connelly,et al.  Robust determination of the fibre orientation distribution in diffusion MRI: Non-negativity constrained super-resolved spherical deconvolution , 2007, NeuroImage.

[8]  H. Duffau,et al.  Dorsal Fronto‐Parietal Connections of the Human Brain: A Fiber Dissection Study of Their Composition and Anatomical Relationships , 2012, Anatomical record.

[9]  J Hajnal,et al.  Perinatal cortical growth and childhood neurocognitive abilities , 2011, Neurology.

[10]  D. V. Essen,et al.  A tension-based theory of morphogenesis and compact wiring in the central nervous system , 1997, Nature.

[11]  K. Sneppen,et al.  Specificity and Stability in Topology of Protein Networks , 2002, Science.

[12]  Daniel Rueckert,et al.  A common neonatal image phenotype predicts adverse neurodevelopmental outcome in children born preterm , 2010, NeuroImage.

[13]  H. Lagercrantz,et al.  The functional architecture of the infant brain as revealed by resting-state fMRI. , 2011, Cerebral cortex.

[14]  Jonathan D. Power,et al.  Evidence for Hubs in Human Functional Brain Networks , 2013, Neuron.

[15]  P. Rakić,et al.  Changes of synaptic density in the primary visual cortex of the macaque monkey from fetal to adult stage , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[16]  Keith A. Johnson,et al.  Cortical Hubs Revealed by Intrinsic Functional Connectivity: Mapping, Assessment of Stability, and Relation to Alzheimer's Disease , 2009, The Journal of Neuroscience.

[17]  Zoltán Toroczkai,et al.  The role of long-range connections on the specificity of the macaque interareal cortical network , 2013, Proceedings of the National Academy of Sciences.

[18]  P. Goldman-Rakic,et al.  Preface: Cerebral Cortex Has Come of Age , 1991 .

[19]  Daniel Rueckert,et al.  Identifying population differences in whole-brain structural networks: A machine learning approach , 2010, NeuroImage.

[20]  M. Turner,et al.  Postnatal Head Growth in Preterm Infants: A Randomized Controlled Parenteral Nutrition Study , 2014, Pediatrics.

[21]  E. Bullmore,et al.  A Resilient, Low-Frequency, Small-World Human Brain Functional Network with Highly Connected Association Cortical Hubs , 2006, The Journal of Neuroscience.

[22]  I. S. Gousias,et al.  Whole-brain mapping of structural connectivity in infants reveals altered connection strength associated with growth and preterm birth. , 2014, Cerebral cortex.

[23]  N. Jovanov-Milošević,et al.  The development of cerebral connections during the first 20-45 weeks' gestation. , 2006, Seminars in fetal & neonatal medicine.

[24]  O. Sporns,et al.  Structural and Functional Aspects Relating to Cost and Benefit of Rich Club Organization in the Human Cerebral Cortex , 2013, Cerebral cortex.

[25]  Conor Liston,et al.  Atypical Prefrontal Connectivity in Attention-Deficit/Hyperactivity Disorder: Pathway to Disease or Pathological End Point? , 2011, Biological Psychiatry.

[26]  J. Changeux,et al.  The Emergence of Human Consciousness: From Fetal to Neonatal Life , 2009, Pediatric Research.

[27]  O. Sporns,et al.  The economy of brain network organization , 2012, Nature Reviews Neuroscience.

[28]  F. Turkheimer,et al.  Emergence of resting state networks in the preterm human brain , 2010, Proceedings of the National Academy of Sciences.

[29]  Alan Connelly,et al.  Direct estimation of the fiber orientation density function from diffusion-weighted MRI data using spherical deconvolution , 2004, NeuroImage.

[30]  O. Sporns,et al.  Rich Club Organization of Macaque Cerebral Cortex and Its Role in Network Communication , 2012, PloS one.

[31]  Biyu J. He,et al.  Breakdown of Functional Connectivity in Frontoparietal Networks Underlies Behavioral Deficits in Spatial Neglect , 2007, Neuron.

[32]  J. Gilmore,et al.  Infant Brain Atlases from Neonates to 1- and 2-Year-Olds , 2011, PloS one.

[33]  Dinggang Shen,et al.  Development Trends of White Matter Connectivity in the First Years of Life , 2011, PloS one.

[34]  O Sporns,et al.  Predicting human resting-state functional connectivity from structural connectivity , 2009, Proceedings of the National Academy of Sciences.

[35]  D. Pandya,et al.  Striatal connections of the parietal association cortices in rhesus monkeys , 1993, The Journal of comparative neurology.

[36]  P. Rakić,et al.  Axon overproduction and elimination in the corpus callosum of the developing rhesus monkey , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[37]  Hiroyuki Kidokoro,et al.  Alterations in brain structure and neurodevelopmental outcome in preterm infants hospitalized in different neonatal intensive care unit environments. , 2014, The Journal of pediatrics.

[38]  O. Sporns,et al.  High-cost, high-capacity backbone for global brain communication , 2012, Proceedings of the National Academy of Sciences.

[39]  Colin Blakemore,et al.  Regressive events in the postnatal development of association projections in the visual cortex , 1985, Nature.

[40]  Sébastien Ourselin,et al.  Preterm birth affects the developmental synergy between cortical folding and cortical connectivity observed on multimodal MRI , 2014, NeuroImage.

[41]  Hao Huang,et al.  Development of axonal pathways in the human fetal fronto‐limbic brain: histochemical characterization and diffusion tensor imaging , 2010, Journal of anatomy.

[42]  O. Sporns,et al.  Rich-Club Organization of the Human Connectome , 2011, The Journal of Neuroscience.

[43]  Anqi Qiu,et al.  Structural connectivity asymmetry in the neonatal brain , 2013, NeuroImage.

[44]  Alessandro Vespignani,et al.  Detecting rich-club ordering in complex networks , 2006, physics/0602134.

[45]  Jin Fan,et al.  Effective Connectivity of the Fronto-parietal Network during Attentional Control , 2010, Journal of Cognitive Neuroscience.

[46]  Olaf Sporns,et al.  Complex network measures of brain connectivity: Uses and interpretations , 2010, NeuroImage.

[47]  Stephen M. Smith,et al.  Threshold-free cluster enhancement: Addressing problems of smoothing, threshold dependence and localisation in cluster inference , 2009, NeuroImage.

[48]  P. Goldman-Rakic,et al.  The primate mediodorsal (MD) nucleus and its projection to the frontal lobe , 1985, The Journal of comparative neurology.

[49]  Daniel Rueckert,et al.  Construction of a consistent high-definition spatio-temporal atlas of the developing brain using adaptive kernel regression , 2012, NeuroImage.

[50]  Daniel Rueckert,et al.  The Effect of Preterm Birth on Thalamic and Cortical Development , 2011, Cerebral cortex.

[51]  Daniel Rueckert,et al.  A Probabilistic Framework to Infer Brain Functional Connectivity from Anatomical Connections , 2011, IPMI.

[52]  Joseph V. Hajnal,et al.  Development of cortical microstructure in the preterm human brain , 2013, Proceedings of the National Academy of Sciences.

[53]  O. Sporns,et al.  Identification and Classification of Hubs in Brain Networks , 2007, PloS one.

[54]  Sampsa Vanhatalo,et al.  Early development of spatial patterns of power-law frequency scaling in FMRI resting-state and EEG data in the newborn brain. , 2013, Cerebral cortex.

[55]  Mark W. Woolrich,et al.  Probabilistic diffusion tractography with multiple fibre orientations: What can we gain? , 2007, NeuroImage.

[56]  R. Kahn,et al.  Functionally linked resting‐state networks reflect the underlying structural connectivity architecture of the human brain , 2009, Human brain mapping.

[57]  Michael Small,et al.  Rich-club connectivity dominates assortativity and transitivity of complex networks , 2010, Physical review. E, Statistical, nonlinear, and soft matter physics.

[58]  Emi Takahashi,et al.  Emerging cerebral connectivity in the human fetal brain: an MR tractography study. , 2012, Cerebral cortex.

[59]  O. Sporns,et al.  White matter maturation reshapes structural connectivity in the late developing human brain , 2010, Proceedings of the National Academy of Sciences.

[60]  Emma K. Towlson,et al.  The Rich Club of the C. elegans Neuronal Connectome , 2013, The Journal of Neuroscience.

[61]  Rebecca D Folkerth,et al.  Axonal development in the cerebral white matter of the human fetus and infant , 2005, The Journal of comparative neurology.

[62]  D. J. Felleman,et al.  Distributed hierarchical processing in the primate cerebral cortex. , 1991, Cerebral cortex.

[63]  Jonathan D. Power,et al.  Prediction of Individual Brain Maturity Using fMRI , 2010, Science.

[64]  Giorgio M. Innocenti,et al.  Exuberance in the development of cortical networks , 2005, Nature Reviews Neuroscience.

[65]  J. Cummings.  Frontal-subcortical circuits and human behavior. , 1998, Archives of neurology.

[66]  Christopher P. Hess,et al.  A DTI-Based Template-Free Cortical Connectome Study of Brain Maturation , 2013, PloS one.

[67]  Peter Fransson,et al.  Resting-state networks in the infant brain , 2007, Proceedings of the National Academy of Sciences.

[68]  H. Kinney,et al.  Sequence of Central Nervous System Myelination in Human Infancy. II. Patterns of Myelination in Autopsied Infants , 1988, Journal of neuropathology and experimental neurology.

[69]  Alex Arenas,et al.  From Modular to Centralized Organization of Synchronization in Functional Areas of the Cat Cerebral Cortex , 2010, PloS one.

[70]  R. Malenka,et al.  Coordinated Changes in Dendritic Arborization and Synaptic Strength during Neural Circuit Development , 2009, Neuron.