Individual differences in neonatal white matter are associated with executive function at 3 years of age

The development of executive function (EF) in early childhood contributes to social and academic aspects of school readiness and facilitates emerging self-regulatory competence. Numerous efforts are underway to identify aspects of early brain development that contribute to emerging EF. Existing research supports the importance of multiple white matter tracts for EF in older children and adults. However, this research has not been extended to young children. In this study, we consider neonatal white matter microstructure in relation to children’s performance on a battery of EF tasks three years later. We obtained diffusion tensor imaging data from a sample of neonates (N = 27) shortly after birth. At 3 years of age, children completed a computerized battery of EF tasks. The primary data analyses involved regression models estimated for each white matter tract. Multiple demographic and measure-related covariates were included in each model. A follow-up analysis of tracts determined to be associated with EF examined individual data points along those fibers. Among the white matter tracts analyzed, the cingulum was significantly associated with EF at 3 years of age. Specifically, lower axial diffusivity values along the cingulum were associated with increased performance on the EF battery. Results are discussed as providing initial evidence that individual differences in neonatal brain structure may facilitate the acquisition of EF abilities in early childhood. These findings are consistent with previous research that supports the value of the cingulum for higher-order cognitive abilities. Cautions and implications of these results are considered

Reduced brain mammillary body volumes and memory deficits in adolescents who have undergone the Fontan procedure.

BackgroundAdolescents with single ventricle heart disease (SVHD) who have undergone the Fontan procedure show cognitive/memory deficits. Mammillary bodies are key brain sites that regulate memory; however, their integrity in SVHD is unclear. We evaluated mammillary body (MB) volumes and their associations with cognitive/memory scores in SVHD and controls.MethodsBrain MRI data were collected from 63 adolescents (25 SVHD; 38 controls) using a 3.0-Tesla MRI scanner. Cognition and memory were assessed using Montreal Cognitive Assessment (MoCA) and Wide Range Assessment of Memory and Learning 2. MB volumes were calculated and compared between groups (ANCOVA, covariates: age, sex, and total brain volume [TBV]). Partial correlations and linear regression were performed to examine associations between volumes and cognitive scores (covariates: age, sex, and TBV).ResultsSVHD group showed significantly lower MoCA and WRAML2 scores over controls. MB volumes were significantly reduced in SVHD over controls. After controlling for age, sex, and TBV, MB volumes correlated with MoCA and delayed memory recall scores in SVHD and controls.ConclusionAdolescents with SVHD show reduced MB volumes associated with cognitive/memory deficits. Potential mechanisms of volume losses may include developmental and/or hypoxic/ischemic-induced processes. Providers should screen for cognitive deficits and explore possible interventions to improve memory

Inflammatory biomarkers and brain health indicators in children with overweight and obesity: The ActiveBrains project

INTRODUCTION: Chronic inflammation plays an important role on the pathogenesis of several cardiovascular and metabolic diseases, as well as on brain function and behaviour. The aim of the present study was to examine the associations between inflammatory biomarkers and a wide range of brain health indicators (i.e., academic performance, executive function, behavioural and emotional functioning, and brain volume) in children with overweight/obesity. METHODS: A total of 107 children (10.0 ± 1.1 years, 41% girls) from the ActiveBrains project were included in the analysis. Five inflammatory biomarkers were analysed in plasma: white blood cell (WBC) count, interleukin-6 (IL-6), interleukin-1beta, tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP). Academic performance was assessed by Woodcock-Munoz Tests of Achievement. Executive function was assessed through the Design Fluency Test for cognitive flexibility, the Stroop test for cognitive inhibition, and the Delayed Non-Match-to-Sample task for working memory. Behavioural and emotional functioning was evaluated through the Behavior Assessment System for Children (BASC) questionnaire. Total and regional brain volume was assessed by magnetic resonance imaging. RESULTS: IL-6 was inversely associated with adaptive skills (beta = -0.228; p = 0.030), while TNF-alpha was related to mathematics (beta = -0.198; p = 0.034). In addition, CRP was positively associated with externalizing (beta = 0.246; p = 0.046) and internalizing problems (beta = 0.234; p = 0.039), as well as the behavioural symptoms index (beta = 0.236; p = 0.047). However, these significant associations disappeared after multiple comparisons correction. Inflammatory biomarkers were not associated with executive function and total brain volumes. Regarding regional brain analyses, WBC was positively associated with gray matter volume in the left middle temporal gyrus (beta = 0.387; p < 0.001, k = 44), and CRP was positively associated with gray matter volume in the right superior temporal gyrus (beta = 0.439; p < 0.001, k = 29). Additionally, when adjusting by total brain volume, CRP was positively associated with gray matter volume in the right supplementary motor cortex (beta = 0.453; p < 0.001, k = 51). Moreover, both, IL-6 (beta = 0.366; p < 0.001, k = 81) and TNF-alpha (beta = 0.368; p < 0.001, k = 62) were positively associated with white matter volume around the right inferior frontal gyrus pars opercularis, while CRP was inversely associated with white matter volume around the left superior frontal gyrus (beta = -0.482; p < 0.001, k = 82). After adjusting by total brain volume, CRP was also inversely associated with white matter volume in 3 additional clusters (beta ranging from -0.473 to -0.404; p < 0.001, k = 87). CONCLUSIONS: Inflammation was slightly associated with brain health (i.e., academic performance, behavioural and emotional functioning and regional brain volume) in children with overweight or obesity. Further larger longitudinal and interventional studies are warranted to elucidate the short-term and long-term effect of systemic low-grade inflammation on children's brain health

Impaired visual short-term memory capacity is distinctively associated with structural connectivity of the posterior thalamic radiation and the splenium of the corpus callosum in preterm-born adults

Preterm birth is associated with an increased risk for lasting changes in both the cortico-thalamic system and attention; however, the link between cortico-thalamic and attention changes is as yet little understood. In preterm newborns, cortico-cortical and cortico-thalamic structural connectivity are distinctively altered, with increased local clustering for cortico-cortical and decreased integrity for cortico-thalamic connectivity. In preterm-born adults, among the various attention functions, visual short-term memory (vSTM) capacity is selectively impaired. We hypothesized distinct associations between vSTM capacity and the structural integrity of cortico-thalamic and cortico-cortical connections, respectively, in preterm-born adults. A whole-report paradigm of briefly presented letter arrays based on the computationally formalized Theory of Visual Attention (TVA) was used to quantify parameter vSTM capacity in 26 preterm- and 21 full-term-born adults. Fractional anisotropy (FA) of posterior thalamic radiations and the splenium of the corpus callosum obtained by diffusion tensor imaging were analyzed by tract-based spatial statistics and used as proxies for cortico-thalamic and cortico-cortical structural connectivity. The relationship between vSTM capacity and cortico-thalamic and cortico-cortical connectivity, respectively, was significantly modified by prematurity. In full-term-born adults, the higher FA in the right posterior thalamic radiation the higher vSTM capacity; in preterm-born adults this FA-vSTM-relationship was inversed. In the splenium, higher FA was correlated with higher vSTM capacity in preterm-born adults, whereas no significant relationship was evident in full-term-born adults. These results indicate distinct associations between cortico-thalamic and cortico-cortical integrity and vSTM capacity in preterm-and full-term-born adults. Data suggest compensatory cortico-cortical fiber re-organization for attention deficits after preterm delivery

SOCIOECONOMIC AND NEUROANATOMIC CONTRIBUTIONS TO LANGUAGE PERFORMANCE IN CHILDREN BORN VERY PRETERM AT PRESCHOOL AND SCHOOL AGE

Background: Children born very preterm are more likely to have difficulties with language acquisition and use that persist throughout childhood. Preterm birth occurs at a critical time in brain development and interrupts neurodevelopment, which has downstream implications for altered neural structure and function. Prematurity and socioeconomic status greatly impact language performance in children, but the neural substrates are poorly understood. Here the neural constituents of language performance are examined in select cortical and subcortical regions. Methods: Fifty-one children born preterm (24-31 weeks) and 20 born full-term were seen at preschool (mean age = 47 months) and school age (mean age = 74 months). Diverse aspects of language performance were evaluated at preschool and school age and were also aggregated into a single score using principle components analysis. At preschool age, measures of cortical thickness, surface area, subcortical volumes, and fractional anisotropy of white matter tracts were calculated for select frontotemporal regions implicated in language. Caregivers reported on many sociodemographic variables which were reduced using principle components analysis. Repeated measures general linear models were used to examine group differences in language performance and to determine the contributions of group, socioeconomic status, and neuroanatomical substrates to language performance. Results: Children born very preterm performed more poorly than children born full-term on tests of receptive language, verbal fluency and verbal working memory at preschool and school age. Five measures of language performance were reduced to one principle component at both preschool and school age. Socioeconomic status significantly accounted for language performance across groups and time points. Initial neuroanatomical analyses found that subcortical volumes significantly accounted for language performance. Analyses of language performance including neuroanatomy and socioeconomic status revealed that socioeconomic status had a significant main effect, as did some specific measures of cortical thickness, subcortical volumes and white matter tracts. Conclusions: Our findings provide support for poorer language performance in children born very preterm at preschool and school age. The relationship between structural neuroanatomic variations associated with preterm birth and language deficits is supported by our findings that language performance was significantly associated with subcortical volumes. This result highlights the possible importance of corticostriatal learning circuits in poorer language performance in children born very preterm. Importantly, our findings that socioeconomic status substantially accounted for language performance also emphasizes the multifactorial determinants of language problems in preterm birth, which is still poorly understood despite decades of research. Finally, these results have important implications for early intervention on an individual level, as well as policy reform to improve the broader social conditions and medical resources needed by so many Americans

White matter microstructural development and cognitive ability in the first 2 years of life

White matter (WM) integrity has been related to cognitive ability in adults and children, but it remains largely unknown how WM maturation in early life supports emergent cognition. The associations between tract-based measures of fractional anisotropy (FA) and axial and radial diffusivity (AD, RD) shortly after birth, at age 1, and at age 2 and cognitive measures at 1 and 2 years were investigated in 447 healthy infants. We found that generally higher FA and lower AD and RD across many WM tracts in the first year of life were associated with better performance on measures of general cognitive ability, motor, language, and visual reception skills at ages 1 and 2, suggesting an important role for the overall organization, myelination, and microstructural properties of fiber pathways in emergent cognition. RD in particular was consistently related to ability, and protracted development of RD from ages 1 to 2 years in several tracts was associated with higher cognitive scores and better language performance, suggesting prolonged plasticity may confer cognitive benefits during the second year of life. However, we also found that cognition at age 2 was weakly associated with WM properties across infancy in comparison to child and demographic factors including gestational age and maternal education. Our findings suggest that early postnatal WM integrity across the brain is important for infant cognition, though its role in cognitive development should be considered alongside child and demographic factors

Language ability in preterm children is associated with arcuate fasciculi microstructure at term

In the mature human brain, the arcuate fasciculus mediates verbal working memory, word learning, and sublexical speech repetition. However, its contribution to early language acquisition remains unclear. In this work, we aimed to evaluate the role of the direct segments of the arcuate fasciculi in the early acquisition of linguistic function. We imaged a cohort of 43 preterm born infants (median age at birth of 30 gestational weeks; median age at scan of 42 postmenstrual weeks) using high b value high-angular resolution diffusion-weighted neuroimaging and assessed their linguistic performance at 2 years of age. Using constrained spherical deconvolution tractography, we virtually dissected the arcuate fasciculi and measured fractional anisotropy (FA) as a metric of white matter development. We found that term equivalent FA of the left and right arcuate fasciculi was significantly associated with individual differences in linguistic and cognitive abilities in early childhood, independent of the degree of prematurity. These findings suggest that differences in arcuate fasciculi microstructure at the time of normal birth have a significant impact on language development and modulate the first stages of language learning

Born too early and too small: higher order cognitive function and brain at risk at ages 8–16

Prematurity presents a risk for higher order cognitive functions. Some of these deficits manifest later in development, when these functions are expected to mature. However, the causes and consequences of prematurity are still unclear. We conducted a longitudinal study to first identify clinical predictors of ultrasound brain abnormalities in 196 children born very preterm (VP; gestational age 32 weeks) and with very low birth weight (VLBW; birth weight 1500 g). At ages 8–16, the subset of VP-VLBW children without neurological findings (124) were invited for a neuropsychological assessment and an MRI scan (41 accepted). Of these, 29 met a rigorous criterion for MRI quality and an age, and gender-matched control group (n = 14) was included in this study. The key findings in the VP-VLBW neonates were: (a) 37% of the VP-VLBW neonates had ultrasound brain abnormalities; (b) gestational age and birth weight collectively with hospital course (i.e., days in hospital, neonatal intensive care, mechanical ventilation and with oxygen therapy, surgeries, and retinopathy of prematurity) predicted ultrasound brain abnormalities. At ages 8–16, VP-VLBW children showed: a) lower intelligent quotient (IQ) and executive function; b) decreased gray and white matter (WM) integrity; (c) IQ correlated negatively with cortical thickness in higher order processing cortical areas. In conclusion, our data indicate that facets of executive function and IQ are the most affected in VP-VLBW children likely due to altered higher order cortical areas and underlying WMThis study was supported by the Spanish Government Institute Carlos III (FIS Pl11/02860), Spanish Ministry of Health to MM-L, and the University of Castilla-La Mancha mobility Grant VA1381500149

Language ability in preterm children is associated with arcuate fasciculi microstructure at term.

In the mature human brain, the arcuate fasciculus mediates verbal working memory, word learning, and sublexical speech repetition. However, its contribution to early language acquisition remains unclear. In this work, we aimed to evaluate the role of the direct segments of the arcuate fasciculi in the early acquisition of linguistic function. We imaged a cohort of 43 preterm born infants (median age at birth of 30 gestational weeks; median age at scan of 42 postmenstrual weeks) using high b value high-angular resolution diffusion-weighted neuroimaging and assessed their linguistic performance at 2 years of age. Using constrained spherical deconvolution tractography, we virtually dissected the arcuate fasciculi and measured fractional anisotropy (FA) as a metric of white matter development. We found that term equivalent FA of the left and right arcuate fasciculi was significantly associated with individual differences in linguistic and cognitive abilities in early childhood, independent of the degree of prematurity. These findings suggest that differences in arcuate fasciculi microstructure at the time of normal birth have a significant impact on language development and modulate the first stages of language learning. Hum Brain Mapp 38:3836-3847, 2017. © 2017 Wiley Periodicals, Inc