The case of late preterm birth: sliding forwards the critical window for cognitive outcome risk

Many survivors of preterm birth experience neurodevelopmental disabilities, such as cerebral palsy, visual and hearing problems. However, even in the absence of major neurological complications, premature babies show significant neuropsychological and behavioural deficits during childhood and beyond. While the clinical tools routinely used to assess neurocognitive development in those infants have been useful in detecting major clinical complications in early infancy, they have not been equally sensitive in identifying subtle cognitive impairments emerging during childhood. These methodological concerns become even more relevant when considering the case of late preterm children (born between 34 and 36 gestational weeks). Although these children have been traditionally considered as having similar risks for developmental problems as neonates born at term, a recent line of research has provided growing evidence that even late preterm children display altered structural and functional brain maturation, with potential life-long implications for neurocognitive functioning. A recent study by Heinonen put forward the hypothesis that environmental factors, in this case educational attainment, could moderate the association between late preterm birth (LPT) and neuropsychological impairments commonly associated with aging. In this paper we bring together clinical literature and recent neuroimaging evidence in order to provide two different but complementary approaches for a better understanding of the "nature-nurture" interplay underlying the lifespan neurocognitive development of preterm babies

Studying the brain from adolescence to adulthood through sparse multi-view matrix factorisations

Men and women differ in specific cognitive abilities and in the expression of several neuropsychiatric conditions. Such findings could be attributed to sex hormones, brain differences, as well as a number of environmental variables. Existing research on identifying sex-related differences in brain structure have predominantly used cross-sectional studies to investigate, for instance, differences in average gray matter volumes (GMVs). In this article we explore the potential of a recently proposed multi-view matrix factorisation (MVMF) methodology to study structural brain changes in men and women that occur from adolescence to adulthood. MVMF is a multivariate variance decomposition technique that extends principal component analysis to "multi-view" datasets, i.e. where multiple and related groups of observations are available. In this application, each view represents a different age group. MVMF identifies latent factors explaining shared and age-specific contributions to the observed overall variability in GMVs over time. These latent factors can be used to produce low-dimensional visualisations of the data that emphasise age-specific effects once the shared effects have been accounted for. The analysis of two datasets consisting of individuals born prematurely as well as healthy controls provides evidence to suggest that the separation between males and females becomes increasingly larger as the brain transitions from adolescence to adulthood. We report on specific brain regions associated to these variance effects.Comment: Submitted to the 6th International Workshop on Pattern Recognition in Neuroimaging (PRNI

Altered Cortical Gyrification in Adults Who Were Born Very Preterm and Its Associations With Cognition and Mental Health

Background: The last trimester of pregnancy is a critical period for the establishment of cortical gyrification, and altered folding patterns have been reported following very preterm birth (\u3c 33 weeks of gestation) in childhood and adolescence. However, research is scant on the persistence of such alterations in adulthood and their associations with cognitive and psychiatric outcomes. Methods: We studied 79 very preterm and 81 age-matched full-term control adults. T1-weighted magnetic resonance images were used to measure a local gyrification index (LGI), indicating the degree of folding across multiple vertices of the reconstructed cortical surface. Group and group-by-sex LGI differences were assessed by means of per-vertex adjustment for cortical thickness and overall intracranial volume. Within-group correlations were also computed between LGI and functional outcomes, including general intelligence (IQ) and psychopathology. Results: Very preterm adults had significantly reduced LGI in extensive cortical regions encompassing the frontal, anterior temporal, and occipitoparietal lobes. Alterations in lateral fronto-temporal-parietal and medial occipitoparietal regions were present in both men and women, although men showed more extensive alterations. In both very preterm and control adults, higher LGI was associated with higher IQ and lower psychopathology scores, with the spatial distribution of these associations substantially differing between the two groups. Conclusions: Very preterm adults’ brains are characterized by significant and widespread local hypogyria, and these alterations might be implicated in cognitive and psychiatric outcomes. Gyrification reflects an early developmental process and provides a fingerprint for very preterm birth

A multimodal imaging study of recognition memory in very preterm born adults

Very preterm (<32 weeks of gestation) birth is associated with structural brain alterationsand memory impairments throughout childhood and adolescence. Here, we used functional MRI(fMRI) to study the neuroanatomy of recognition memory in 49 very preterm-born adults and 50 con-trols (mean age: 30 years) during completion of a task involving visual encoding and recognition ofabstract pictures. T1-weighted and diffusion-weighted images were also collected. Bilateral hippocam-pal volumes were calculated and tractography of the fornix and cingulum was performed and assessedin terms of volume and hindrance modulated orientational anisotropy (HMOA). Online recognitionmemory task performance, assessed with A scores, was poorer in the very preterm compared with thecontrol group. Analysis of fMRI data focused on differences in neural activity between the recognitionand encoding trials. Very preterm born adults showed decreased activation in the right middle frontalgyrus and posterior cingulate cortex/precuneus and increased activation in the left inferior frontalgyrus and bilateral lateral occipital cortex (LOC) compared with controls. Hippocampi, fornix and cin-gulum volume was significantly smaller and fornix HMOA was lower in very preterm adults. Amongall the structural and functional brain metrics that showed statistically significant group differences,LOC activation was the best predictor of online task performance (P 5 0.020). In terms of associationbetween brain function and structure, LOC activation was predicted by fornix HMOA in the pretermgroup only (P 5 0.020). These results suggest that neuroanatomical alterations in very preterm bornindividuals may be underlying their poorer recognition memory performance

Alterations in cortical thickness development in preterm-born individuals:Implications for high-order cognitive functions

AbstractVery preterm birth (gestational age <33weeks) is associated with alterations in cortical thickness and with neuropsychological/behavioural impairments. Here we studied cortical thickness in very preterm born individuals and controls in mid-adolescence (mean age 15years) and beginning of adulthood (mean age 20years), as well as longitudinal changes between the two time points. Using univariate approaches, we showed both increases and decreases in cortical thickness in very preterm born individuals compared to controls. Specifically (1) very preterm born adolescents displayed extensive areas of greater cortical thickness, especially in occipitotemporal and prefrontal cortices, differences which decreased substantially by early adulthood; (2) at both time points, very preterm-born participants showed smaller cortical thickness, especially in parahippocampal and insular regions. We then employed a multivariate approach (support vector machine) to study spatially discriminating features between the two groups, which achieved a mean accuracy of 86.5%. The spatially distributed regions in which cortical thickness best discriminated between the groups (top 5%) included temporal, occipitotemporal, parietal and prefrontal cortices. Within these spatially distributed regions (top 1%), longitudinal changes in cortical thickness in left temporal pole, right occipitotemporal gyrus and left superior parietal lobe were significantly associated with scores on language-based tests of executive function. These results describe alterations in cortical thickness development in preterm-born individuals in their second decade of life, with implications for high-order cognitive processing

Early development of structural networks and the impact of prematurity on brain connectivity

Preterm infants are at high risk of neurodevelopmental impairment, which may be due to altered development of brain connectivity. We aimed to (i) assess structural brain development from 25 to 45 weeks gestational age (GA) using graph theoretical approaches and (ii) test the hypothesis that preterm birth results in altered white matter network topology. Sixty-five infants underwent MRI between 25(+3) and 45(+6) weeks GA. Structural networks were constructed using constrained spherical deconvolution tractography and were weighted by measures of white matter microstructure (fractional anisotropy, neurite density and orientation dispersion index). We observed regional differences in brain maturation, with connections to and from deep grey matter showing most rapid developmental changes during this period. Intra-frontal, frontal to cingulate, frontal to caudate and inter-hemispheric connections matured more slowly. We demonstrated a core of key connections that was not affected by GA at birth. However, local connectivity involving thalamus, cerebellum, superior frontal lobe, cingulate gyrus and short range cortico-cortical connections was related to the degree of prematurity and contributed to altered global topology of the structural brain network. The relative preservation of core connections at the expense of local connections may support more effective use of impaired white matter reserve following preterm birth

Neonatal Brain Injury and Neuroanatomy of Memory Processing following Very Preterm Birth in Adulthood: An fMRI Study

Altered functional neuroanatomy of high-order cognitive processing has been described in very preterm individuals (born before 33 weeks of gestation; VPT) compared to controls in childhood and adolescence. However, VPT birth may be accompanied by different types of adverse neonatal events and associated brain injury, the severity of which may have differential effects on brain development and subsequent neurodevelopmental outcome. We conducted a functional magnetic resonance imaging (fMRI) study to investigate how differing degrees of neonatal brain injury, detected by neonatal ultrasounds, affect the functional neuroanatomy of memory processing in VPT young adults. We used a verbal paired associates learning task, consisting of four encoding, four cued-recall and four baseline condition blocks. To further investigate whether differences in neural activation between the groups were modulated by structural brain changes, structural MRI data were also collected. We studied 12 VPT young adults with a history of periventricular haemorrhage with associated ventricular dilatation, 17 VPT individuals with a history of uncomplicated periventricular haemorrhage, 12 individuals with normal ultrasonographic findings, and 17 controls. Results of a linear trend analysis demonstrated that during completion of the paired associates learning task right frontal and right parietal brain activation decreased as the severity of neonatal brain injury increased. There were no statistically significant between-group differences in on-line task performance and participants' intelligence quotient (IQ) at assessment. This pattern of differential activation across the groups was observed particularly in the right middle frontal gyrus during encoding and in the right posterior cingulate gyrus during recall. Structural MRI data analysis revealed that grey matter volume in the right superior temporal gyrus, right cerebellum, left middle temporal gyrus, right globus pallidus and right medial frontal gyrus decreased with increasing severity of neonatal brain injury. However, the significant between-group functional neuroanatomical differences were not directly attributable to the detected structural regional differences

White Matter and Cognition in Adults Who Were Born Preterm

BACKGROUND AND PURPOSE: Individuals born very preterm (before 33 weeks of gestation, VPT) are at risk of damage to developing white matter, which may affect later cognition and behaviour. METHODS: We used diffusion tensor MRI (DT-MRI) to assess white matter microstructure (fractional anisotropy; FA) in 80 VPT and 41 term-born individuals (mean age 19.1 years, range 17-22, and 18.5 years, range 17-22 years, respectively). VPT individuals were part of a 1982-1984 birth cohort which had been followed up since birth; term individuals were recruited by local press advertisement. General intellectual function, executive function and memory were assessed. RESULTS: The VPT group had reduced FA in four clusters, and increased FA in four clusters relative to the Term group, involving several association tracts of both hemispheres. Clusters of increased FA were associated with more severe neonatal brain injury in the VPT group. Clusters of reduced FA were associated with lower birth weight and perinatal hypoxia, and with reduced adult cognitive performance in the VPT group only. CONCLUSIONS: Alterations of white matter microstructure persist into adulthood in VPT individuals and are associated with cognitive function