Deanne K. Thompson

Preterm infant hippocampal volumes correlate with later working memory deficits

Children born preterm exhibit working memory deficits. These deficits may be associated with structural brain changes observed in the neonatal period. In this study, the relationship between neonatal regional brain volumes and working memory deficits at age 2 years were investigated, with a particular interest in the dorsolateral prefrontal cortex, parietal cortex and the hippocampus. While the eligible sample consisted of 227 very preterm children who were born at the Royal Womens Hospital, Melbourne prior to 30 weeks gestation or weighing <1250 g, 156 children had complete data sets. Neonatal magnetic resonance images of the brain were obtained at term equivalent age and subsequently parcellated into eight sub-regions, while the hippocampus was manually segmented. The relationship between brain volumes for these regions and performance on a working memory task (delayed alternation) at 2 years of age was examined. Very preterm children who perseverated on the working memory task had significantly smaller hippocampal volumes than very preterm children who exhibited intact working memory, even after adjusting for relevant perinatal, sociodemographic and developmental factors. Preterm children appear to have altered hippocampal volumes by discharge from hospital which may have a lasting impact on working memory function.

Neonate hippocampal volumes: Prematurity, perinatal predictors, and 2‐year outcome

To compare preterm (PT) and full‐term (FT) infant hippocampal volumes and to investigate the relations among PT hippocampal volume, perinatal risk factors, and neurodevelopmental outcome.

Characterization of the corpus callosum in very preterm and full-term infants utilizing MRI

The corpus callosum is the largest white matter tract, important for interhemispheric communication. The aim of this study was to investigate and compare corpus callosum size, shape and diffusion characteristics in 106 very preterm infants and 22 full-term infants. Structural and diffusion magnetic resonance images were obtained at term equivalent. The corpus callosum was segmented, cross-sectional areas were calculated, and shape was analyzed. Fractional anisotropy, mean, axial and radial diffusivity measures were obtained from within the corpus callosum, with additional probabilistic tractography analysis. Very preterm infants had significantly reduced callosal cross-sectional area compared with term infants (p=0.004), particularly for the mid-body and posterior sub-regions. Very preterm callosi were more circular (p=0.01). Fractional anisotropy was lower (p=0.007) and mean (p=0.006) and radial (p=0.001) diffusivity values were higher in very preterm infants callosi, particularly at the anterior and posterior ends. The volume of tracts originating from the corpus callosum was reduced in very preterm infants (p=0.001), particularly for anterior mid-body (p=0.01) and isthmus tracts (p=0.04). This study characterizes callosal size, shape and diffusion in typically developing infants at term equivalent age, and reports macrostructural and microstructural abnormalities as a result of prematurity.

Corpus callosum alterations in very preterm infants: perinatal correlates and 2 year neurodevelopmental outcomes

The aim of this study was to relate altered corpus callosum (CC) integrity in 106 very preterm (VPT) infants (<30 weeks gestational age or <1250 g birth weight) at term equivalent to perinatal predictors and neurodevelopmental outcomes at two years. T1 and diffusion magnetic resonance images were obtained. The CC was traced, and divided into six sub-regions for cross-sectional area and shape analyses. Fractional anisotropy, mean, axial and radial diffusivity were sampled within the CC, and probabilistic tractography was performed. Perinatal predictors were explored. The Bayley Scales of Infant Development (BSID-II) was administered at two years. Intraventricular hemorrhage was associated with a smaller genu and altered diffusion values within the anterior and posterior CC of VPT infants. White matter injury was associated with widespread alterations to callosal diffusion values, especially posteriorly, and radial diffusivity was particularly elevated, indicating altered myelination. Reduced CC tract volume related to lower gestational age, particularly posteriorly. Reduced posterior callosal skew was associated with postnatal corticosteroid exposure. This more circular CC was associated with delayed cognitive development. Higher diffusivity, particularly in splenium tracts, was associated with impaired motor development. This study elucidates perinatal predictors and adverse neurodevelopmental outcomes associated with altered callosal integrity in VPT infants.

Regional white matter microstructure in very preterm infants: Predictors and 7 year outcomes

The aims of this study were to investigate regional white matter microstructural differences between very preterm (VPT) (<30 weeks gestational age and/or <1250xa0g) and full term (FT) (≥37 weeks gestational age) infants at term corrected age with diffusion tensor imaging, and to explore perinatal predictors of diffusion measures, and the relationship between regional diffusion measures and neurodevelopmental outcomes at age 7 years in VPT children. Mean (MD) (pxa0=xa0.003), axial (AD) (pxa0=xa0.008), and radial diffusivity (RD) (pxa0=xa0.003) in total white matter were increased in VPT compared with FT infants, with similar fractional anisotropy (FA) in the two groups. There was little evidence that group-wise differences were specific to any of the 8 regions studied for each hemisphere. Perinatal white matter abnormality and intraventricular hemorrhage (grade III or IV) were associated with increased diffusivity in the white matter of VPT infants. Higher white matter diffusivity measures of the inferior occipital and cerebellar region at term-equivalent age were associated with increased risk of impairments in motor and executive function at 7 years in VPT children, but there was little evidence for associations with IQ or memory impairment. In conclusion, myelination is likely disrupted or delayed in VPT infants, especially those with perinatal brain abnormality (BA). Altered diffusivity at term-equivalent age helps explain impaired functioning at 7 years. This study defines the nature of microstructural alterations in VPT infant white matter, assists in understanding the associated risk factors, and is the first study to reveal an important link between inferior occipital and cerebellar white matter disorganization in infancy, and executive and motor functioning 7 years later.

MR-determined hippocampal asymmetry in full-term and preterm neonates.

Hippocampi are asymmetrical in children and adults, where the right hippocampus is larger. To date, no literature has confirmed that hippocampal asymmetry is evident at birth. Furthermore, gender differences have been observed in normal hippocampal asymmetry, but this has not been examined in neonates. Stress, injury, and lower IQ have been associated with alterations to hippocampal asymmetry. These same factors often accompany preterm birth. Therefore, prematurity is possibly associated with altered hippocampal asymmetry. There were three aims of this study: First, we assessed whether hippocampi were asymmetrical at birth, second whether there was a gender effect on hippocampal asymmetry, and third whether the stress of preterm birth altered hippocampal asymmetry. This study utilized volumetric magnetic resonance imaging to compare left and right hippocampal volumes in 32 full‐term and 184 preterm infants at term. Full‐term infants demonstrated rightward hippocampal asymmetry, as did preterm infants. In the case of preterm infants, hippocampal asymmetry was proportional to total hemispheric asymmetry. This study is the first to demonstrate that the normal pattern of hippocampal asymmetry is present this early in development. We did not find gender differences in hippocampal asymmetry at term. Preterm infants tended to have less asymmetrical hippocampi than full‐term infants, a difference which became significant after correcting for hemispheric brain tissue volumes. This study may suggest that hippocampal asymmetry develops in utero and is maintained into adulthood in infants with a normal neurological course.

Hippocampal shape variations at term equivalent age in very preterm infants compared with term controls: Perinatal predictors and functional significance at age 7

The hippocampus undergoes rapid growth and development in the perinatal months. Infants born very preterm (VPT) are vulnerable to hippocampal alterations, and can provide a model of disturbed early hippocampal development. Hippocampal shape alterations have previously been associated with memory impairment, but have never been investigated in infants. The aims of this study were to determine hippocampal shape differences between 184 VPT infants (<30 weeks gestation or <1250 g at birth) and 32 full-term infants, effects of perinatal factors, and associations between infant hippocampal shape and volume, and 7 year verbal and visual memory (California Verbal Learning Test - Childrens Version and Dot Locations). Infants underwent 1.5 T magnetic resonance imaging at term equivalent age. Hippocampi were segmented, and spherical harmonics-point distribution model shape analysis was undertaken. VPT infants hippocampi were less infolded than full-term infants, being less curved toward the midline and less arched superior-inferiorly. Straighter hippocampi were associated with white matter injury and postnatal corticosteroid exposure. There were no significant associations between infant hippocampal shape and 7 year memory measures. However, larger infant hippocampal volumes were associated with better verbal memory scores. Altered hippocampal shape in VPT infants at term equivalent age may reflect delayed or disrupted development. This study provides further insight into early hippocampal development and the nature of hippocampal abnormalities in prematurity.

Hippocampal volume and memory and learning outcomes at 7 years in children born very preterm.

Using magnetic resonance imaging, this study compared hippocampal volume between 145 very preterm children and 34 children born full-term at 7 years of age. The relationship between hippocampal volume and memory and learning impairments at 7 years was also investigated. Manual hippocampal segmentation and subsequent three-dimensional volumetric analysis revealed reduced hippocampal volumes in very preterm children compared with term peers. However, this relationship did not remain after correcting for whole brain volume and neonatal brain abnormality. Contrary to expectations, hippocampal volume in the very preterm cohort was not related to memory and learning outcomes. Further research investigating the effects of very preterm birth on more extensive networks in the brain that support memory and learning in middle childhood is needed.

Alterations in the optic radiations of very preterm children—Perinatal predictors and relationships with visual outcomes

Children born very preterm (VPT) are at risk for visual impairments, the main risk factors being retinopathy of prematurity and cerebral white matter injury, however these only partially account for visual impairments in VPT children. This study aimed to compare optic radiation microstructure and volume between VPT and term-born children, and to investigate associations between 1) perinatal variables and optic radiations; 2) optic radiations and visual function in VPT children. We hypothesized that optic radiation microstructure would be altered in VPT children, predicted by neonatal cerebral white matter abnormality and retinopathy of prematurity, and associated with visual impairments. 142 VPT children and 32 controls underwent diffusion-weighted magnetic resonance imaging at 7 years of age. Optic radiations were delineated using constrained spherical deconvolution tractography. Tract volume and average diffusion tensor values for the whole optic radiations and three sub-regions were compared between the VPT and control groups, and correlated with perinatal variables and 7-year visual outcome data. Total tract volumes and average diffusion values were similar between VPT and control groups. On regional analysis of the optic radiation, mean and radial diffusivity were higher within the middle sub-regions in VPT compared with control children. Neonatal white matter abnormalities and retinopathy of prematurity were associated with optic radiation diffusion values. Lower fractional anisotropy in the anterior sub-regions was associated with poor visual acuity and increased likelihood of other visual defects. This study presents evidence for microstructural alterations in the optic radiations of VPT children, which are largely predicted by white matter abnormality or severe retinopathy of prematurity, and may partially explain the higher rate of visual impairments in VPT children.

Longitudinal growth and morphology of the hippocampus through childhood: Impact of prematurity and implications for memory and learning.

The effects of prematurity on hippocampal development through early childhood are largely unknown. The aims of this study were to (1) compare the shape of the very preterm (VPT) hippocampus to that of full‐term (FT) children at 7 years of age, and determine if hippocampal shape is associated with memory and learning impairment in VPT children, (2) compare change in shape and volume of the hippocampi from term‐equivalent to 7 years of age between VPT and FT children, and determine if development of the hippocampi over time predicts memory and learning impairment in VPT children. T1 and T2 magnetic resonance images were acquired at both term equivalent and 7 years of age in 125 VPT and 25 FT children. Hippocampi were manually segmented and shape was characterized by boundary point distribution models at both time‐points. Memory and learning outcomes were measured at 7 years of age. The VPT group demonstrated less hippocampal infolding than the FT group at 7 years. Hippocampal growth between infancy and 7 years was less in the VPT compared with the FT group, but the change in shape was similar between groups. There was little evidence that the measures of hippocampal development were related to memory and learning impairments in the VPT group. This study suggests that the developmental trajectory of the human hippocampus is altered in VPT children, but this does not predict memory and learning impairment. Further research is required to elucidate the mechanisms for memory and learning difficulties in VPT children. Hum Brain Mapp 35:4129–4139, 2014.