Development of cortical microstructure in the preterm human brain

Abstract

Cortical maturation was studied in 65 infants between 27 and 46 wk postconception using structural and diffusion magnetic resonance imaging. Alterations in neural structure and complexity were inferred from changes in mean diffusivity and fractional anisotropy, analyzed by sampling regions of interest and also by a unique whole-cortex mapping approach. Mean diffusivity was higher in gyri than sulci and in frontal compared with occipital lobes, decreasing consistently throughout the study period. Fractional anisotropy declined until 38 wk, with initial values and rates of change higher in gyri, frontal and temporal poles, and parietal cortex; and lower in sulcal, perirolandic, and medial occipital cortex. Neuroanatomical studies and experimental diffusion-anatomic correlations strongly suggested the interpretation that cellular and synaptic complexity and density increased steadily throughout the period, whereas elongation and branching of dendrites orthogonal to cortical columns was later and faster in higher-order association cortex, proceeding rapidly before becoming undetectable after 38 wk. The rate of microstructural maturation correlated locally with cortical growth, and predicted higher neurodevelopmental test scores at 2 y of age. Cortical microstructural development was reduced in a dose-dependent fashion by longer premature exposure to the extrauterine environment, and preterm infants at term-corrected age possessed less mature cortex than term-born infants. The results are compatible with predictions of the tension theory of cortical growth and show that rapidly developing cortical microstructure is vulnerable to the effects of premature birth, suggesting a mechanism for the adverse effects of preterm delivery on cognitive function. brain development | DTI | preterm birth D endritic arborization and synapse formation increase within the cerebral cortical plate from midgestation, transforming the cortex from a predominantly radial formation arrayed perpendicular to the cortical surface into a denser, more complex structure with large numbers of neural connections running parallel to the surface (1). Several groups have related this microstructural maturation to changes in the rate and principal direction of water diffusion within the cortex observed in vivo by diffusion tensor imaging (DTI) (2-5). It is proposed that increasing cellular density and complexity lead to a decrease in tissue water content and a fall in mean diffusivity (MD) (6-9), whereas decreases in the relative fraction of water diffusion perpendicular to the cortical surface, measured as a decline in fractional anisotropy (FA), reflect neurite outgrowth and maturing dendritic cytoarchitecture (7,8,(10)(11)(12). These changes have been measured in neonatal piglets (13), cats (14), and mice (15), and in pioneering studies of preterm infants (3,4,8).The present study used structural MRI and DTI to examine the spatial and temporal development of human cortical microstructure. We reasoned that if the process was impaired by preterm birth we...

Multimodal image analysis of clinical influences on preterm brain development

“…Notably, this pattern was independent of preceding clinical‐image relationships and also total ICV. This multimodal imaging marker was striking in the relative sparing of primary cortex, which may reflect the relative maturity of primary cortex at this age,8 and in the changes in diffusivity in the lentiform nuclei, which may reflect altered cell density. Animal models of preterm birth have shown that prolonged respiratory ventilation is associated with adverse cerebral outcomes, including tissue volume loss and white matter injury,46 and we have previously demonstrated global volume losses and alterations to white matter microstructure in infants with chronic lung disease 35, 47.…”

The developing human connectome project: A minimal processing pipeline for neonatal cortical surface reconstruction

“…Numerous works have been published in the literature that have improved our understanding of the perinatal brain (Ball et al, 2013b(Ball et al, , 2017Counsell et al, 2013;Doria et al, 2010;Kapellou et al, 2006;Keunen et al, 2017;Krishnan et al, 2017;Xue et al, 2007;Dubois et al, 2008a,b;Pienaar et al, 2008;RodriguezCarranza et al, 2008;Awate et al, 2010;Hill et al, 2010;Rathbone et al, 2011;Moeskops et al, 2013;Li et al, 2014b,a;Meng et al, 2014;Nie et al, 2014;Wang et al, 2014;Engelhardt et al, 2015;Lefevre et al, 2015;Li et al, 2015b;Moeskops et al, 2015;Li et al, 2016;Hazlett et al, 2017). Study- ing the developing connectome will open up many opportunities in future, not least because neonatal brain imaging data is changing rapidly, at scales that can be clearly resolved using current MRI technology.…”

“…During this time, the cellular foundations of our advanced cognitive abilities are mapped out, as connections start to form between distant regions (Ball et al, 2013b;Van Essen, 1997), myelinating, and later pruning, at different rates. Alongside the development of this neural infrastructure, functional brain activations start to be resolved (Doria et al, 2010), reflecting the development of cognition.…”

“…Much of what is currently known about the early human connectome has been learnt from models of preterm growth (Ball et al, 2013b;Counsell et al, 2013;Doria et al, 2010;Keunen et al, 2017). Whilst invaluable, it is known that early exposure to the extra-uterine environment has longterm implications (Ball et al, 2012(Ball et al, , 2013a(Ball et al, , 2017Counsell et al, 2014;Hintz et al, 2015;Ullman et al, 2015).…”

Specialization and integration of functional thalamocortical connectivity in the human infant

“…This anatomical distribution of areas affected by prematurity may reflect known developmental programming: microstructural maturation of primary sensory cortex seems to occur earlier than heteromodal cortex (37), and growth association protein, which is present in growing axons but lost when stable connections are made (47), is absent from axonal connections to first-order relays (44) but persists in regions of heteromodal cortex, where it may mediate experience-dependent plasticity (48). Cortical areas receiving inputs from first-order thalamic relays also mature earliest with regards to myelin formation and cortical thickness (49), whereas thalamocortical units found in this study to be affected by prematurity involve cortex which takes the longest to reach peak cortical thickness (50).…”