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

Maturing Thalamocortical Functional Connectivity Across Development

Recent years have witnessed a surge of investigations examining functional brain organization using resting-state functional connectivity MRI (rs-fcMRI). To date, this method has been used to examine systems organization in typical and atypical developing populations. While the majority of these investigations have focused on cortical–cortical interactions, cortical–subcortical interactions also mature into adulthood. Innovative work by Zhang et al. (2008) in adults have identified methods that utilize rs-fcMRI and known thalamo-cortical topographic segregation to identify functional boundaries in the thalamus that are remarkably similar to known thalamic nuclear grouping. However, despite thalamic nuclei being well formed early in development, the developmental trajectory of functional thalamo-cortical relations remains unexplored. Thalamic maps generated by rs-fcMRI are based on functional relationships, and should modify with the dynamic thalamo-cortical changes that occur throughout maturation. To examine this possibility, we employed a strategy as previously described by Zhang et al. to a sample of healthy children, adolescents, and adults. We found strengthening functional connectivity of the cortex with dorsal/anterior subdivisions of the thalamus, with greater connectivity observed in adults versus children. Temporal lobe connectivity with ventral/midline/posterior subdivisions of the thalamus weakened with age. Changes in sensory and motor thalamo-cortical interactions were also identified but were limited. These findings are consistent with known anatomical and physiological cortical–subcortical changes over development. The methods and developmental context provided here will be important for understanding how cortical–subcortical interactions relate to models of typically developing behavior and developmental neuropsychiatric disorders

Exploring the Rôle of White Matter Connectivity in Cortex Maturation

De nombreuses études ont mis en évidence un processus de maturation séquentiel pour différentes régions cérébrales, notamment la matière grise corticale et ses connections de matière blanche (WM). Cependant, les mécanismes à l’origine du processus de maturation cérébrale, ainsi que la relation entre la maturation des ces deux structures demeurent mal compris. Dans cette étude, nous utilisons l’imagerie par résonance magnétique (IRM) pour obtenir simultanément des informations reflétant la maturation microstructurelle des différentes structures cérébrales, ainsi que la mise en place des connections de matière blanche durant le développement précoce. Pour ce faire, nous employons deux mesures d’IRM bien établies reflétant les changements microstructurels liés à la maturation, soit le coefficient de diffusion apparent (ADC) et le temps de relaxation T (T1), ainsi que des algorithmes mathématiques permettant de reconstruire les groupes d’axones reliant différentes régions de matière grise (connectome). Ce travail démontre une interdépendance entre la maturation des structures de matière grise corticale et le développement de l’arbre connectionel de matière blanche sous-jacent. En effet, nous mettons en évidence un degré de maturation analogue entre les régions corticales, ainsi que les groupes de fibres axonales associées durant les stades précoces de la maturation. Un tel lien est également observé entre deux régions corticales reliées par un groupe de fibres. Sur la base de ces observations, cette étude propose un modèle mathématique et informatique simple parlant pour un rôle clé des structures de matière blanche dans le relai des signaux maturationnels depuis un stimuli externe via les structures primaires sensorielles et atteignant finalement les structures cérébrales corticales d’ordre plus complexes. -- The maturation of the cortical gray matter (GM) and white matter (WM) are described as sequential processes following multiple, but distinct rules. However, neither the mecha- nisms driving brain maturation processes, nor the relationship between GM and WM matu- ration are well understood. Here we use connectomics and two MRI measures reflecting maturation related changes in cerebral microstructure, namely the Apparent Diffusion Coef- ficient (ADC) and the T1 relaxation time (T1), to study brain development. We report that the advancement of GM and WM maturation are inter-related and depend on the underlying brain connectivity architecture. Particularly, GM regions and their incident WM connections show corresponding maturation levels, which is also observed for GM regions connected through a WM tract. Based on these observations, we propose a simple computational model supporting a key role for the connectome in propagating maturation signals sequen- tially from external stimuli, through primary sensory structures to higher order functional cortices

Exploring the role of white matter connectivity in cortex maturation.

The maturation of the cortical gray matter (GM) and white matter (WM) are described as sequential processes following multiple, but distinct rules. However, neither the mechanisms driving brain maturation processes, nor the relationship between GM and WM maturation are well understood. Here we use connectomics and two MRI measures reflecting maturation related changes in cerebral microstructure, namely the Apparent Diffusion Coefficient (ADC) and the T1 relaxation time (T1), to study brain development. We report that the advancement of GM and WM maturation are inter-related and depend on the underlying brain connectivity architecture. Particularly, GM regions and their incident WM connections show corresponding maturation levels, which is also observed for GM regions connected through a WM tract. Based on these observations, we propose a simple computational model supporting a key role for the connectome in propagating maturation signals sequentially from external stimuli, through primary sensory structures to higher order functional cortices

Rethinking Phylogeny and Ontogeny in Hominin Brain Evolution

Theories of hominin and human cognitive evolution have traditionally focused on the phylogeny of the human brain, and on comparisons of human and primate brains in relation to social or ecological variables. Far less attention has been paid to ontogenetic processes, despite the recognition that experience has a profound influence on adult cognition. In this paper we discuss the interplay between phylogeny and ontogeny by examining relationships between human brain size, developmental scheduling and cognition. The correlates of large brains include not only altered subsistence and life-history strategies to meet associated energetic costs, but also on macro- and micro-scale structural adaptations required to meet increased processing costs. This means that larger brains are of necessity more highly interconnected brains, with higher degrees of folding of the neocortex (gyrification) and higher ratios of myelinated connections between neurons (white matter) to neurons themselves (grey matter). Here we argue that the combination of these evolutionary trends underpins the complexity of human behaviour, as the neural circuits involved in cognitive mechanisms such as the mirror neuron system (the system governing motor emulation and imitation) and theory of mind (fundamental in social cognition) mature only slowly, and require considerable socially-scaffolded experience to develop to their full potential. These abilities are likely to be fundamental in characteristically human behaviours such as the cultural transmission of complex forms of tool manufacture and use, attested to in the archaeological record. Their elaborated modern human forms, we argue, are possible only in the context of the evolution of relatively slower trajectories of brain growth and hence longer periods during which the growing brain can be influenced by experience among modern humans relative to other primates. Here we review some of the differences in ontogenetic brain development between humans and other primates, and compare the rates and trajectories of neural development between ourselves and our closest living relatives the chimpanzees to suggest that the human pattern of expanded periods of growth coupled with slower trajectories of neural development is likely to have been of huge significance during hominin evolution. In addition, we discuss fossil and archaeological proxies which might allow the reconstruction of evolutionary patterns of development, suggesting that it is only post-Homo erectus and specifically among Homo heidelbergensis and Homo neanderthalensis populations that developmental patterns approximate those of modern humans, arguing for a similar – but not identical – role for socially-scaffolded learning of complex technical skills as among modern groups in these species

MR connectomics: a conceptual framework for studying the developing brain

The combination of advanced neuroimaging techniques and major developments in complex network science, have given birth to a new framework for studying the brain: “connectomics.” This framework provides the ability to describe and study the brain as a dynamic network and to explore how the coordination and integration of information processing may occur. In recent years this framework has been used to investigate the developing brain and has shed light on many dynamic changes occurring from infancy through adulthood. The aim of this article is to review this work and to discuss what we have learned from it. We will also use this body of work to highlight key technical aspects that are necessary in general for successful connectome analysis using today's advanced neuroimaging techniques. We look to identify current limitations of such approaches, what can be improved, and how these points generalize to other topics in connectome research

Longitudinal maturation of auditory cortical function during adolescence

Cross-sectional studies have demonstrated that the cortical auditory evoked potential (CAEP) changes substantially in amplitude and latency from childhood to adulthood, suggesting that these aspects of the CAEP continue to mature through adolescence. However, no study to date has longitudinally followed maturation of these CAEP measures through this developmental period. Additionally, no study has examined the trial-to-trial variability of the CAEP during adolescence. Therefore, we longitudinally tracked changes in the latency, amplitude, and variability of the P1, N1, P2, and N2 components of the CAEP in 68 adolescents from age 14 years to age 17 years. Latency decreased for N1 and N2, and did not change for P1 or P2. Amplitude decreased for P1 and N2, increased for N1, and did not change for P2. Variability decreased with age for all CAEP components. These findings provide longitudinal support for the view that the human auditory system continues to mature through adolescence. Continued auditory system maturation through adolescence suggests that CAEP neural generators remain plastic during this age range and potentially amenable to experience-based enhancement or deprivation

Effects of adolescent alcohol binge drinking on prefrontal myelin

Alcohol binge drinking is highly prevalent in teenagers and is associated with various harmful health effects and social problems. During adolescence, brain regions such as the prefrontal cortex (PFC) are still undergoing active development, characterized by increases in white matter volume. While the morphological details and the cellular and molecular sequences governing adolescent white matter development are not fully known, it is known that this development process is sensitive and can be disrupted. Although consumption of alcohol in a binge drinking pattern has been linked to lower white matter integrity in humans, it is important to determine if alcohol is causing this change or if predisposing factors can influence drinking. A rodent model of voluntary binge drinking was used to elicit high alcohol intake during a short developmental window in adolescence. Myelin was then assessed using several histochemical measures. Results showed that adolescent development is marked by an increase in myelinated fibers in the PFC that accompanied an increase in conduction velocity, and alcohol reduces prefrontal white matter and myelinated fiber density. In addition, heavy drinking was associated with long-term cognitive deficits. I also investigated sex differences in the effects of adolescent alcohol consumption on PFC myelination, showing that males appear to be more vulnerable than females. The findings altogether increase our understanding of the developmental process of prefrontal myelination in adolescence and the maladaptive effects alcohol can have on this critical process