Functional thalamocortical connectivity at term equivalent age and outcome at 2 years in infants born preterm

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Evidence from in vivo 31-phosphorus magnetic resonance spectroscopy phosphodiesters that exhaled ethane is a biomarker of cerebral n-3 polyunsaturated fatty acid peroxidation in humans

<p>Abstract</p> <p>Background</p> <p>This study tested the hypothesis that exhaled ethane is a biomarker of cerebral <it>n</it>-3 polyunsaturated fatty acid peroxidation in humans. Ethane is released specifically following peroxidation of <it>n</it>-3 polyunsaturated fatty acids. We reasoned that the cerebral source of ethane would be the docosahexaenoic acid component of membrane phospholipids. Breakdown of the latter also releases phosphorylated polar head groups, giving rise to glycerophosphorylcholine and glycerophosphorylethanolamine, which can be measured from the 31-phosphorus neurospectroscopy phosphodiester peak. Schizophrenia patients were chosen because of evidence of increased free radical-mediated damage and cerebral lipid peroxidation in this disorder.</p> <p>Methods</p> <p>Samples of alveolar air were obtained from eight patients and ethane was analyzed and quantified by gas chromatography and mass spectrometry (<it>m</it>/<it>z </it>= 30). Cerebral 31-phosphorus spectra were obtained from the same patients at a magnetic field strength of 1.5 T using an image-selected <it>in vivo </it>spectroscopy sequence (TR = 10 s; 64 signal averages localized on a 70 × 70 × 70 mm³voxel). The quantification of the 31-phosphorus signals using prior knowledge was carried out in the temporal domain after truncating the first 1.92 ms of the signal to remove the broad component present in the 31-phosphorus spectra.</p> <p>Results</p> <p>The ethane and phosphodiester levels, expressed as a percentage of the total 31-phosphorus signal, were positively and significantly correlated (<it>r</it>_{<it>s </it>}= 0.714, <it>p </it>< 0.05).</p> <p>Conclusion</p> <p>Our results support the hypothesis that the measurement of exhaled ethane levels indexes cerebral <it>n</it>-3 lipid peroxidation. From a practical viewpoint, if human cerebral <it>n</it>-3 polyunsaturated fatty acid catabolism can be measured by ethane in expired breath, this would be more convenient than determining the area of the 31-phosphorus neurospectroscopy phosphodiester peak.</p

Maturation of sensori-motor functional responses in the preterm brain

†Authors contributed equally to the work and have shared first authorship. Preterm birth engenders an increased risk of conditions like cerebral palsy and therefore this timemay be crucial for the brain’s developing sensori-motor system. However, little is known about how cortical sensori-motor function matures at this time, whether development is influencedbyexperience, andabout its role in spontaneousmotor behavior.Weaimed to systematically characterize spatial and temporal maturation of sensori-motor functional brain activity across this period using functional MRI and a custom-made robotic stimulation device. We studied 57 infants aged from 30+ 2 to 43 + 2 weeks postmenstrual age. Following both induced and spontaneous right wrist movements, we saw consistent positive blood oxygen level–dependent functional responses in the contralateral (left) primary somatosensory and motor cortices. In addition, we saw a maturational trend toward faster, higher amplitude, and more spatially dispersed functional responses; and increasing integration of the ipsilateral hemisphere and sensori-motor associative areas. We also found that interhemispheric functional connectivity was significantly related to ex-utero exposure, suggesting the influence of experience-dependent mechanisms. At term equivalent age, we saw a decrease in both response amplitude and interhemispheric functional connectivity, and an increase in spatial specificity, culminating in the establishment of a sensori-motor functional response similar to that seen in adults

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

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

Advanced magnetic resonance imaging detects altered placental development in pregnancies affected by congenital heart disease

Congenital heart disease (CHD) is the most common congenital malformation and is associated with adverse neurodevelopmental outcomes. The placenta is crucial for healthy fetal development and placental development is altered in pregnancy when the fetus has CHD. This study utilized advanced combined diffusion-relaxation MRI and a data-driven analysis technique to test the hypothesis that placental microstructure and perfusion are altered in CHD-affected pregnancies. 48 participants (36 controls, 12 CHD) underwent 67 MRI scans (50 control, 17 CHD). Significant differences in the weighting of two independent placental and uterine-wall tissue components were identified between the CHD and control groups (both pFDR < 0.001), with changes most evident after 30 weeks gestation. A significant trend over gestation in weighting for a third independent tissue component was also observed in the CHD cohort (R = 0.50, pFDR = 0.04), but not in controls. These findings add to existing evidence that placental development is altered in CHD. The results may reflect alterations in placental perfusion or the changes in fetal-placental flow, villous structure and maturation that occur in CHD. Further research is needed to validate and better understand these findings and to understand the relationship between placental development, CHD, and its neurodevelopmental implications

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