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

Memory deficits following neonatal critical illness: A common neurodevelopmental pathway

Summary Over the last decade, knowledge has emerged that children growing up after neonatal critical illness, irrespective of underlying diagnosis, are at risk of memory impairment and school problems. Strikingly, these problems are manifest even when intelligence is normal. In this review, we propose a common neurodevelopmental pathway following neonatal critical illness by demonstrating that the survivors of preterm birth, congenital heart disease, and severe respiratory failure, share an increased risk of long-term memory deficits and associated hippocampal alterations. Rather than being a consequence of underlying diagnosis, we suggest that this shared vulnerability is most likely related to common conditions associated with neonatal critical illness. These include hypoxia, neuroinflammation, stress, exposure to anaesthetics, or a complex interplay of these factors at different postconceptional ages. Future work should be aimed at improving early identification of patients at risk and evaluating intervention modalities, such as cognitive or exercise training

Alteraciones neuropsicológicas y daño cerebral en la infancia y adolescencia asociados al nacimiento prematuro

Prematurity is defined by the World Health Organization (WHO, 1977) as a delivery occurring before 37 completed weeks of gestation. White matter (WM) abnormalities and periventricular leukomalacia (PVL) are the most prominent pathologies in the preterm neonate. Compared with their term-peers, children born preterm have lower intelligence quotient (IQ) scores, although within the normal range. Moreover, domain-specific measures of neuropsychological abilities such as executive functions, visuoperceptual and linguistic skills are often impaired. Preterm children with PVL have a similar profile, with lower IQ scores and poorer executive functions, mental calculation and visuoperceptual skills than controls. Cerebral structural gray matter (GM) abnormalities that might contribute to the poor performance of preterm samples are localized in the frontal, parietal, temporal and occipital lobes. The cerebellum and deep gray matter structures such as the caudate nuclei, the thalami and the hippocampus are also altered. Over the past few years, magnetic resonance imaging and neuropathological studies have shown that, in addition to the classical WM injury seen in preterm samples with PVL, cortical and subcortical GM injury may also contribute to the impaired cognitive performance.La prematuridad es definida por la Organización Mundial de la Salud (OMS, 1977) como el parto que ocurre antes de las 37 semanas de gestación. La alteración de la sustancia blanca (SB) es la principal característica de daño cerebral y la leucomalacia periventricular (LPV) es el hallazgo patológico más común en estudios de resonancia magnética Los niños nacidos prematuros comparados con los niños nacidos a término presentan un cociente de inteligencia (CI) con puntuaciones menores pero dentro de la normalidad. Las funciones neuropsicológicas específicas más afectadas son las ejecutivas, visuo-perceptivas y lingüísticas. Los niños prematuros con LPV, también muestran puntuaciones más bajas en el CI, en las funciones ejecutivas, en el cálculo mental y en las capacidades visuoperceptivas. Las alteraciones cerebrales estructurales de sustancia gris (SG) que pueden contribuir a una peor ejecución cognitiva en estas muestras de prematuros implican regiones en los lóbulos cerebrales temporal, parietal, frontal y occipital. Además, el cerebelo y diversos núcleos grises subcorticales tales como el núcleo caudado, el tálamo y el hipocampo están también afectados. En los últimos años, los estudios de resonancia magnética y neuropatológicos, están demostrando que además de la alteración clásica de SB, los niños prematuros con LPV presentan daño en la SG tanto cortical como subcortical a los cuales se les atribuye una implicación directa en la peor ejecución cognitiva

Alteraciones neuropsicológicas y daño cerebral en la infancia y adolescencia asociados al nacimiento prematuro

Prematurity is defined by the World Health Organization (WHO, 1977) as a delivery occurring before 37 completed weeks of gestation. White matter (WM) abnormalities and periventricular leukomalacia (PVL) are the most prominent pathologies in the preterm neonate. Compared with their term-peers, children born preterm have lower intelligence quotient (IQ) scores, although within the normal range. Moreover, domain-specific measures of neuropsychological abilities such as executive functions, visuoperceptual and linguistic skills are often impaired. Preterm children with PVL have a similar profile, with lower IQ scores and poorer executive functions, mental calculation and visuoperceptual skills than controls. Cerebral structural gray matter (GM) abnormalities that might contribute to the poor performance of preterm samples are localized in the frontal, parietal, temporal and occipital lobes. The cerebellum and deep gray matter structures such as the caudate nuclei, the thalami and the hippocampus are also altered. Over the past few years, magnetic resonance imaging and neuropathological studies have shown that, in addition to the classical WM injury seen in preterm samples with PVL, cortical and subcortical GM injury may also contribute to the impaired cognitive performance.  La prematuridad es definida por la Organización Mundial de la Salud (OMS, 1977) como el parto que ocurre antes de las 37 semanas de gestación. La alteración de la sustancia blanca (SB) es la principal característica de daño cerebral y la leucomalacia periventricular (LPV) es el hallazgo patológico más común en estudios de resonancia magnética Los niños nacidos prematuros comparados con los niños nacidos a término presentan un cociente de inteligencia (CI) con puntuaciones menores pero dentro de la normalidad. Las funciones neuropsicológicas específicas más afectadas son las ejecutivas visuo-perceptivas y lingüísticas. Los niños prematuros con LPV, también muestran puntuaciones más bajas en el CI, en las funciones ejecutivas, en el cálculo mental y en las capacidades visuoperceptivas. Las alteraciones cerebrales estructurales de sustancia gris (SG) que pueden contribuir a una peor ejecución cognitiva en estas muestras de prematuros implican regiones en los lóbulos cerebrales temporal, parietal, frontal y occipital. Además, el cerebelo y diversos núcleos grises subcorticales tales como el núcleo caudado, el tálamo y el hipocampo están también afectados. En los últimos años, los estudios de resonancia magnética y neuropatológicos, están demostrando que además de la alteración clásica de SB, los niños prematuros con LPV presentan daño en la SG tanto cortical como subcortical a los cuales se les atribuye una implicación directa en la peor ejecución cognitiva

Reduced hippocampal subfield volumes and memory performance in preterm children with and without germinal matrix intraventricular hemorrhage.

Preterm newborns with germinal matrix-intraventricular hemorrhage (GM-IVH) are at a higher risk of evidencing neurodevelopmental alterations. Present study aimed to explore the long-term efects that GM-IVH have on hippocampal subfelds, and their correlates with memory. The sample consisted of 58 participants, including 36 preterm-born (16 with GM-IVH and 20 without neonatal brain injury), and 22 full-term children aged between 6 and 15 years old. All participants underwent a cognitive assessment and magnetic resonance imaging study. GM-IVH children evidenced lower scores in Full Intelligence Quotient and memory measures compared to their low-risk preterm and full-term peers. High-risk preterm children with GM-IVH evidenced signifcantly lower total hippocampal volumes bilaterally and hippocampal subfeld volumes compared to both low-risk preterm and full-term groups. Finally, signifcant positive correlations between memory and hippocampal subfeld volumes were only found in preterm participants together; memory and the right CA-feld correlation remained signifcant after Bonferroni correction was applied (p= .002). In conclusion, memory alterations and both global and regional volumetric reductions in the hippocampus were found to be specifcally related to a preterm sample with GM-IVH. Nevertheless, results also suggest that prematurity per se has a long-lasting impact on the association between the right CA-feld volume and memory during childhood

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

Subregional hippocampal morphology and psychiatric outcome in adolescents who were born very preterm and at term

Background: The hippocampus has been reported to be structurally and functionally altered as a sequel of very preterm birth ( < 33 weeks gestation), possibly due its vulnerability to hypoxic-ischemic damage in the neonatal period. We examined hippocampal volumes and subregional morphology in very preterm born individuals in mid- and late adolescence and their association with psychiatric outcome. Methods: Structural brain magnetic resonance images were acquired at two time points (baseline and follow-up) from 65 ex-preterm adolescents (mean age = 15.5 and 19.6 years) and 36 termborn controls (mean age=15.0 and 19.0 years). Hippocampal volumes and subregional morphometric differences were measured from manual tracings and with three-dimensional shape analysis. Psychiatric outcome was assessed with the Rutter Parents' Scale at baseline, the General Health Questionnaire at follow-up and the Peters Delusional Inventory at both time points. Results: In contrast to previous studies we did not find significant difference in the cross-sectional or longitudinal hippocampal volumes between individuals born preterm and controls, despite preterm individual having significantly smaller whole brain volumes. Shape analysis at baseline revealed subregional deformations in 28% of total bilateral hippocampal surface, reflecting atrophy, in ex-preterm individuals compared to controls, and in 22% at follow-up. In ex-preterm individuals, longitudinal changes in hippocampal shape accounted for 11% of the total surface, while in controls they reached 20%. In the whole sample (both groups) larger right hippocampal volume and bilateral anterior surface deformations at baseline were associated with delusional ideation scores at follow-up. Conclusions: This study suggests a dynamic association between cross-sectional hippocampal volumes, longitudinal changes and surface deformations and psychosis proneness. Copyright

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 W

Hippocampal Volume and Auditory Attention on a Verbal Memory Task with Adult Survivors of Pediatric Brain Tumor

Objective: We examined the nature of verbal memory deficits and the possible hippocampal underpinnings in long-term adult survivors of childhood brain tumor. Method: 35 survivors (M=24.10±4.93 years at testing; 54% female), on average 15 years post-diagnosis, and 59 typically developing adults (M=22.40±4.35 years, 54% female) participated. Automated FMRIB Software Library (FSL) tools were used to measure hippocampal, putamen, and whole brain volumes. The California Verbal Learning Test – Second Edition (CVLT-II) was used to assess verbal memory. Results: Hippocampal (F(1,91)=4.06, ηp2=.04), putamen (F(1,91)=11.18, ηp2=.11), and whole brain (F(1,92)=18.51, ηp2=.17) volumes were significantly lower for survivors than controls (pr=.62, pr=.09; r=.08), for survivors and controls. Verbal memory indices of auditory attention list span (Trial 1) (F (1,92)=12.70, η2=.12) and final list learning (Trial 5) (F (1,92)=6.01, η2=.06) were significantly lower for survivors (pr=.43, p=.01) with auditory attention, but none of the other CVLT-II indices. Secondary analyses for the effect of treatment factors are presented. Conclusion: Volumetric differences between survivors and controls exist for the whole brain and for subcortical structures on average 15 years post-diagnosis. Treatment factors seem to have a unique effect on subcortical structures. Memory differences between survivors and controls are largely contingent upon auditory attention list span. Only hippocampal volume is associated with the auditory attention list span component of verbal memory. These findings are particularly robust for survivors treated with radiation

Low birthweight and preterm birth in young people with special educational needs: a magnetic resonance imaging analysis

<p>Abstract</p> <p>Background</p> <p>Although neuroanatomical and cognitive sequelae of low birthweight and preterm birth have been investigated, little is understood as to the likely prevalence of a history of low birthweight or preterm birth, or neuroanatomical correlates of such a history, within the special educational needs population. Our aim was to address these issues in a sample of young people receiving additional learning support.</p> <p>Methods</p> <p>One hundred and thirty-seven participants aged 13–22 years, receiving additional learning support, were recruited via their schools or colleges and underwent structural magnetic resonance imaging (MRI). Obstetric records, available in 98 cases, included birthweight and gestational data in 90 and 95 cases, respectively. Both qualitative and quantitative voxel-based analyses of MRI data were conducted.</p> <p>Results</p> <p>A history of low birthweight and preterm birth was present in 13.3% and 13.7% of cases, respectively. Low birthweight and preterm birth were associated with specific qualitative anomalies, including enlargement of subarachnoid cisterns and thinning of the corpus callosum. Low birthweight was associated with reduced grey matter density (GMD) in the superior temporal gyrus (STG) bilaterally, left inferior temporal gyrus and left insula. Prematurity of birth was associated with reduced GMD in the STG bilaterally, right inferior frontal gyrus and left cerebellar hemisphere. Comparison of subjects with no history of low birthweight or preterm birth with a previously defined control sample of cognitively unimpaired adolescents (<it>n </it>= 72) demonstrated significantly greater scores for several anomalies, including thinning of the corpus callosum, loss of white matter and abnormalities of shape of the lateral ventricles.</p> <p>Conclusion</p> <p>Although a two-fold increased prevalence of a history of low birthweight and preterm birth exists within the special educational needs population, other aetiological factors must be considered for the overwhelming majority of cases. Neuroanatomical findings within this sample include qualitative anomalies of brain structure and grey matter deficits within temporal lobe structures and the cerebellum that persist into adolescence. These findings suggest a neurodevelopmental mechanism for the cognitive difficulties associated with these obstetric risk factors.</p