White matter maturation profiles through early childhood predict general cognitive ability

Infancy and early childhood are periods of rapid brain development, during which brain structure and function mature alongside evolving cognitive ability. An important neurodevelopmental process during this postnatal period is the maturation of the myelinated white matter, which facilitates rapid communication across neural systems and networks. Though prior brain imaging studies in children (4 years of age and above), adolescents, and adults have consistently linked white matter development with cognitive maturation and intelligence, few studies have examined how these processes are related throughout early development (birth to 4 years of age). Here, we show that the profile of white matter myelination across the first 5 years of life is strongly and specifically related to cognitive ability. Using a longitudinal design, coupled with advanced magnetic resonance imaging, we demonstrate that children with above-average ability show differential trajectories of myelin development compared to average and below average ability children, even when controlling for socioeconomic status, gestation, and birth weight. Specifically, higher ability children exhibit slower but more prolonged early development, resulting in overall increased myelin measures by ~3 years of age. These results provide new insight into the early neuroanatomical correlates of cognitive ability, and suggest an early period of prolonged maturation with associated protracted white matter plasticity may result in strengthened neural networks that can better support later development. Further, these results reinforce the necessity of a longitudinal perspective in investigating typical or suspected atypical cognitive maturation.     

Pediatric neuroimaging using magnetic resonance imaging during non-sedated sleep

Background

Etiological studies of many neurological and psychiatric disorders are increasingly turning toward longitudinal investigations of infant brain development in order to discern predisposing structural and/or functional differences prior to the onset of overt clinical symptoms. While MRI provides a noninvasive window into the developing brain, MRI of infants and toddlers is challenging due to the modality’s extreme motion sensitivity and children’s difficulty in remaining still during image acquisition.

Objective

Here, we outline a broad research protocol for successful MRI of children under 4 years of age during natural, non-sedated sleep.

Materials and methods

All children were imaged during natural, non-sedated sleep. Active and passive measures to reduce acoustic noise were implemented to reduce the likelihood of the children waking up during acquisition. Foam cushions and vacuum immobilizers were used to limit intra-scan motion artifacts.

Results

More than 380 MRI datasets have been successfully acquired from 220 children younger than 4 years of age within the past 39 months. Implemented measures permitted children to remain asleep for the duration of the scan and allowed the data to be acquired with an overall 97% success rate.

Conclusion

The proposed method greatly advances current pediatric imaging techniques and may be readily implemented in other research and clinical settings to facilitate and further improve pediatric neuroimaging.     

Estimating the age of healthy infants from quantitative myelin water fraction maps

The trajectory of the developing brain is characterized by a sequence of complex, nonlinear patterns that occur at systematic stages of maturation. Although significant prior neuroimaging research has shed light on these patterns, the challenge of accurately characterizing brain maturation, and identifying areas of accelerated or delayed development, remains. Altered brain development, particularly during the earliest stages of life, is believed to be associated with many neurological and neuropsychiatric disorders. In this work, we develop a framework to construct voxel‐wise estimates of brain age based on magnetic resonance imaging measures sensitive to myelin content. 198 myelin water fraction (VF_M) maps were acquired from healthy male and female infants and toddlers, 3 to 48 months of age, and used to train a sigmoidal‐based maturational model. The validity of the approach was then established by testing the model on 129 different VF_M datasets. Results revealed the approach to have high accuracy, with a mean absolute percent error of 13% in males and 14% in females, and high predictive ability, with correlation coefficients between estimated and true ages of 0.945 in males and 0.94 in females. This work represents a new approach toward mapping brain maturity, and may provide a more faithful staging of brain maturation in infants beyond chronological or gestation‐corrected age, allowing earlier identification of atypical regional brain development. Hum Brain Mapp 36:1233–1244, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc .     

Synaptosomal Uptake of Alpha-Ketoglutarate and Glutamine in Thioacetamide-Induced Hepatic Encephalopathy in Rats

The kinetics of uptake of two astroglia-derived glutamate (GLU) precursors, α-ketoglutarate (α-KG) and glutamine (GLN) were determined in synaptosomes derived from rats with acute hepatic encephalopathy (HE) induced with a hepatotoxin, thioacetamide (TAA). TAA treatment increased by 33% Vmax for high affinity, low capacity α-KG uptake, without influencing its Km. The increase of the uptake capacity for α-KG may represent a response of the GLUergic nerve terminals to the decreased cerebral α-KG content, which during HE is associated with depressed activity of pyruvate carboxylase, an enzyme that replenishes α-KG in astrocytes. The result is thus consistent with the notion that HE affects the astroglial control of GLUergic neurotransmission. The Km and Vmax for the low affinity, high capacity GLN uptake was not affected by TAA treatment.     

Dietary habits of the middle-aged Warsaw population in 1984 relative to nutritional guidelines.

The dietary habits of 1265 men and 1309 women aged 35-64 years were assessed by food frequencies and 24-h recall. The consumption of fat was high relative to Recommended Dietary Allowances (mean 137% of RDA in the diet of men and 108% in women). The diet was deficient in carbohydrates (80 and 67% respectively), calcium (81 and 64%), vitamin A (84% for both sexes), vitamin B1 (91 and 74%), and vitamin C (41 and 30%). Energy, protein, dietary fibre, iron and vitamin B2 were at the RDA or exceeded it in the men's diet but were insufficient in the women's diet. Fat accounted for 38.5% (men) and 37.7% (women) of energy, with 15.8% of the energy derived from saturated fatty acids and 4.2% from polyunsaturates. The amount of cholesterol consumed was 641 and 452 mg, respectively. This type of diet may contribute to increased incidence of ischaemic heart disease. Only three meals a day were taken by over 83% of the respondents, with over 5-h intervals between meals which may, in addition, contribute to obesity.     

Ocular coloboma: Genetic variants reveal a dynamic model of eye development

Ocular coloboma is a congenital disorder of the eye where a gap exists in the inferior retina, lens, iris, or optic nerve tissue. With a prevalence of 2–19 per 100,000 live births, coloboma, and microphthalmia, an associated ocular disorder, represent up to 10% of childhood blindness. It manifests due to the failure of choroid fissure closure during eye development, and it is a part of a spectrum of ocular disorders that include microphthalmia and anophthalmia. Use of genetic approaches from classical pedigree analyses to next generation sequencing has identified more than 40 loci that are associated with the causality of ocular coloboma. As we have expanded studies to include singleton cases, hereditability has been very challenging to prove. As such, researchers over the past 20 years, have unraveled the complex interrelationship amongst these 40 genes using vertebrate model organisms. Such research has greatly increased our understanding of eye development. These genes function to regulate initial specification of the eye field, migration of retinal precursors, patterning of the retina, neural crest cell biology, and activity of head mesoderm. This review will discuss the discovery of loci using patient data, their investigations in animal models, and the recent advances stemming from animal models that shed new light in patient diagnosis.