Regional gray matter growth, sexual dimorphism, and cerebral asymmetry in the Neonatal Brain

journal articleAlthough there has been recent interest in the study of childhood and adolescent brain development, very little is known about normal brain development in the first few months of life. In older children, there are regional differences in cortical gray matter development, whereas cortical gray and white matter growth after birth has not been studied to a great extent. The adult human brain is also characterized by cerebral asymmetries and sexual dimorphisms, although very little is known about how these asymmetries and dimorphisms develop. We used magnetic resonance imaging and an automatic segmentation methodology to study brain structure in 74 neonates in the first few weeks after birth. We found robust cortical gray matter growth compared with white matter growth, with occipital regions growing much faster than prefrontal regions. Sexual dimorphism is present at birth, with males having larger total brain cortical gray and white matter volumes than females. In contrast to adults and older children, the left hemisphere is larger than the right hemisphere, and the normal pattern of fronto-occipital asymmetry described in older children and adults is not present. Regional differences in cortical gray matter growth are likely related to differential maturation of sensory and motor systems compared with prefrontal executive function after birth. These findings also indicate that whereas some adult patterns of sexual dimorphism and cerebral asymmetries are present at birth, others develop after birth

Prenatal mild ventriculomegaly predicts abnormal development of the neonatal brain

pre-printBackground: Many psychiatric and neurodevelopmental disorders are associated with mild enlargement of the lateral ventricles thought to have origins in prenatal brain development. Little is known about development of the lateral ventricles and the relationship of prenatal lateral ventricle enlargement with postnatal brain development. Methods: We performed a neonatal MRI on 34 children with isolated mild ventriculomegaly (MVM, width of the atrium of the lateral ventricle ≥ 1.0 cm) on prenatal ultrasound and 34 age and gender matched controls with normal prenatal ventricle size. Lateral ventricle and cortical gray and white matter volumes were assessed. Fractional anisotropy (FA) and mean diffusivity (MD) in corpus callosum and cortico-spinal white matter tracts were determined obtained using quantitative tractography . Results: Neonates with prenatal MVM had significantly larger lateral ventricle volumes than matched controls (286.4%; p < 0.0001). Neonates with MVM also had significantly larger intracranial volumes (ICV; 7.1%, p = 0.0063) and cortical gray matter volumes (10.9%, p = 0.0004) compared to controls. DTI tractography revealed a significantly greater MD in the corpus callosum and cortico-spinal tracts, while FA was significantly smaller in several white matter tract regions. Conclusions: Prenatal enlargement of the lateral ventricle is associated with enlargement of the lateral ventricles after birth, as well as greater gray matter volumes and delayed or abnormal maturation of white matter. It is suggested that prenatal ventricle volume is an early structural marker of altered development of the cerebral cortex and may be marker of risk for neuropsychiatric disorders associated with ventricle enlargement

Brain maturation of newborns and infants

pre-printRecently, imaging studies of early human development have received more attention, as improved modeling methods might lead to a clearer understanding of the origin, timing, and nature of differences in neurodevelopmental disorders. Non-invasivemagnetic resonance imaging (MRI) can provide three-dimensional images of the infant brain in less than 20 minutes, with unprecedented anatomical details and contrast of brain anatomy cortical and subcortical structures and brain connectivity.1,2,3 Repeating MRI at different stages of development, e.g., in yearly intervals starting after birth, gives scientists the opportunity to study the trajectory of brain growth and compare individual growth trajectories to normative models. These comparisons become highly relevant in personalized medicine, where early diagnosis is a critical juncture for timing and therapy types

The Commercial Application of Missile/Space Technology, Parts 1 and 2

This report is concerned with the transfer of technology from missile and space programs to non-missile/space applications in the United States. It presents the findings of a University of Denver Research Institute study sponsored by a National Aeronautics and Space Administration (NASA) grant awarded in November 1961. Initial stimulation for the unsolicited proposal leading to this study came from a 1960 Brookings Institution report to NASA, Proposed Studies on the Implications of Peaceful Space Activities for Human Affairs

Functional Connectivity of the Infant Human Brain: Plastic and Modifiable

Infancy is a critical and immensely important period in human brain development. Subtle changes during this stage may be greatly amplified with the unfolding of different developmental processes, exerting far-reaching consequences. Studies of the structure and behavioral manifestations of the infant brain are fruitful. However, the specific functional brain mechanisms that enable the execution of different behaviors remained elusive until the advent of functional connectivity fMRI (fcMRI), which provides an unprecedented opportunity to probe the infant functional brain development in vivo. Since its inception, a burgeoning field of infant brain functional connectivity study has emerged and thrived during the past decade. In this review, we describe (1) findings of normal development of functional connectivity networks and their relationships to behaviors and (2) disruptions of the normative functional connectivity development due to identifiable genetic and/or environmental risk factors during the first 2 years of human life. Technical considerations of infant fcMRI are also provided. It is our hope to consolidate previous findings so that the field can move forward with a clearer picture toward the ultimate goal of fcMRI-based objective methods for early diagnosis/identification of risks and evaluation of early interventions to optimize developing functional connectivity networks in this critical developmental window

Neonatal White Matter Maturation Is Associated With Infant Language Development

Background: While neonates have no sophisticated language skills, the neural basis for acquiring this function is assumed to already be present at birth. Receptive language is measurable by 6 months of age and meaningful speech production by 10-18 months of age. Fiber tracts supporting language processing include the corpus callosum (CC), which plays a key role in the hemispheric lateralization of language; the left arcuate fasciculus (AF), which is associated with syntactic processing; and the right AF, which plays a role in prosody and semantics. We examined if neonatal maturation of these fiber tracts is associated with receptive language development at 12 months of age. Methods: Diffusion-weighted imaging (DWI) was performed in 86 infants at 26.6 ± 12.2 days post-birth. Receptive language was assessed via the MacArthur-Bates Communicative Development Inventory at 12 months of age. Tract-based fractional anisotropy (FA) was determined using the NA-MIC atlas-based fiber analysis toolkit. Associations between neonatal regional FA, adjusted for gestational age at birth and age at scan, and language development at 12 months of age were tested using ANOVA models. Results: After multiple comparisons correction, higher neonatal FA was positively associated with receptive language at 12 months of age within the genu (p < 0.001), rostrum (p < 0.001), and tapetum (p < 0.001) of the CC and the left fronto-parietal AF (p = 0.008). No significant clusters were found in the right AF. Conclusion: Microstructural development of the CC and the AF in the newborn is associated with receptive language at 12 months of age, demonstrating that interindividual variation in white matter microstructure is relevant for later language development, and indicating that the neural foundation for language processing is laid well ahead of the majority of language acquisition. This suggests that some origins of impaired language development may lie in the intrauterine and potentially neonatal period of life. Understanding how interindividual differences in neonatal brain maturity relate to the acquisition of function, particularly during early development when the brain is in an unparalleled window of plasticity, is key to identifying opportunities for harnessing neuroplasticity in health and disease

Varying coefficient model for modeling diffusion tensors along white matter tracts

Diffusion tensor imaging provides important information on tissue structure and orientation of fiber tracts in brain white matter in vivo. It results in diffusion tensors, which are $3\times3$ symmetric positive definite (SPD) matrices, along fiber bundles. This paper develops a functional data analysis framework to model diffusion tensors along fiber tracts as functional data in a Riemannian manifold with a set of covariates of interest, such as age and gender. We propose a statistical model with varying coefficient functions to characterize the dynamic association between functional SPD matrix-valued responses and covariates. We calculate weighted least squares estimators of the varying coefficient functions for the log-Euclidean metric in the space of SPD matrices. We also develop a global test statistic to test specific hypotheses about these coefficient functions and construct their simultaneous confidence bands. Simulated data are further used to examine the finite sample performance of the estimated varying coefficient functions. We apply our model to study potential gender differences and find a statistically significant aspect of the development of diffusion tensors along the right internal capsule tract in a clinical study of neurodevelopment.Comment: Published in at http://dx.doi.org/10.1214/12-AOAS574 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Efficient Probabilistic and Geometric Anatomical Mapping Using Particle Mesh Approximation on GPUs

Deformable image registration in the presence of considerable contrast differences and large size and shape changes presents significant research challenges. First, it requires a robust registration framework that does not depend on intensity measurements and can handle large nonlinear shape variations. Second, it involves the expensive computation of nonlinear deformations with high degrees of freedom. Often it takes a significant amount of computation time and thus becomes infeasible for practical purposes. In this paper, we present a solution based on two key ideas: a new registration method that generates a mapping between anatomies represented as a multicompartment model of class posterior images and geometries and an implementation of the algorithm using particle mesh approximation on Graphical Processing Units (GPUs) to fulfill the computational requirements. We show results on the registrations of neonatal to 2-year old infant MRIs. Quantitative validation demonstrates that our proposed method generates registrations that better maintain the consistency of anatomical structures over time and provides transformations that better preserve structures undergoing large deformations than transformations obtained by standard intensity-only registration. We also achieve the speedup of three orders of magnitudes compared to a CPU reference implementation, making it possible to use the technique in time-critical applications

Twin-singleton developmental study of brain white matter anatomy: Twin-Singleton Developmental Study of Brain White Matter Anatomy

Twin studies provide valuable insights into the analysis of genetic and environmental factors influencing human brain development. However, these findings may not generalize to singletons due to differences in pre- and postnatal environments. One would expect the effect of these differences to be greater during the early years of life. To address this concern, we compare longitudinal diffusion data of white matter regions for 26 singletons and 76 twins (monozygotic and dizygotic) from birth to 2 years of age. We use nonlinear mixed effect modeling where the temporal changes in the diffusion parameters are described by the Gompertz function. The Gompertz function describes growth trajectory in terms of intuitive parameters: asymptote, delay, and speed. We analyzed fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) for 21 regions of interest (ROIs). These ROIs included areas in the association, projection, and commissural fiber tracts. We did not find any differences in the diffusion parameters between monozygotic and dizygotic twins. In addition, FA and RD showed no developmental differences between singletons and twins for the regions analyzed. However, the delay parameter of the Gompertz function of AD for the anterior limb of the internal capsule and anterior corona radiata was significantly different between singletons and twins. Further analysis indicated that the differences are small, and twins “catch up” by the first few months of life. These results suggest that the effects of differences of pre- and postnatal environments between twins and singletons are minimal on white matter development and disappear early in life