An analysis of MRI derived cortical complexity in premature-born adults : regional patterns, risk factors, and potential significance

Premature birth bears an increased risk for aberrant brain development concerning its structure and function. Cortical complexity (CC) expresses the fractal dimension of the brain surface and changes during neurodevelopment. We hypothesized that CC is altered after premature birth and associated with long-term cognitive development. One-hundred-and-one very premature-born adults (gestational age <32 weeks and/or birth weight <1500 ​g) and 111 term-born adults were assessed by structural MRI and cognitive testing at 26 years of age. CC was measured based on MRI by vertex-wise estimation of fractal dimension. Cognitive performance was measured based on Griffiths-Mental-Development-Scale (at 20 months) and Wechsler-Adult-Intelligence-Scales (at 26 years). In premature-born adults, CC was decreased bilaterally in large lateral temporal and medial parietal clusters. Decreased CC was associated with lower gestational age and birth weight. Furthermore, decreased CC in the medial parietal cortices was linked with reduced full-scale IQ of premature-born adults and mediated the association between cognitive development at 20 months and IQ in adulthood. Results demonstrate that CC is reduced in very premature-born adults in temporoparietal cortices, mediating the impact of prematurity on impaired cognitive development. These data indicate functionally relevant long-term alterations in the brain’s basic geometry of cortical organization in prematurity

Sequelae of premature birth in young adults

Background and Purpose Qualitative studies about the abnormalities appreciated on routine magnetic resonance imaging (MRI) sequences in prematurely born adults are lacking. This article aimed at filling this knowledge gap by (1) qualitatively describing routine imaging findings in prematurely born adults, (2) evaluating measures for routine image interpretation and (3) investigating the impact of perinatal variables related to premature birth. Methods In this study two board-certified radiologists assessed T1-weighted and FLAIR-weighted images of 100 prematurely born adults born very preterm (VP <32 weeks) and/or at very low birth weight (VLBW <1500 g) and 106 controls born at full term (FT) (mean age 26.8 ± 0.7 years). The number of white matter lesions (WML) was counted according to localization. Lateral ventricle volume (LVV) was evaluated subjectively and by measurements of Evans’ index (EI) and frontal-occipital-horn ratio (FOHR). Freesurfer-based volumetry served as reference standard. Miscellaneous incidental findings were noted as free text. Results The LVV was increased in 24.7% of VP/VLBW individuals and significantly larger than in FT controls. This was best identified by measurement of FOHR (AUC = 0.928). Ventricular enlargement was predicted by low gestational age (odds ratio: 0.71, 95% CI 0.51–0.98) and presence of neonatal intracranial hemorrhage (odds ratio: 0.26, 95% CI 0.07–0.92). The numbers of deep and periventricular WML were increased while subcortical WMLs were not. Conclusion Enlargement of the LVV and deep and periventricular WMLs are typical sequelae of premature birth that can be appreciated on routine brain MRI. To increase sensitivity of abnormal LVV detection, measurement of FOHR seems feasible in clinical practice

A different appetite for sovereignty? Independence movements in subnational island jurisdictions

Local autonomy in a subnational jurisdiction is more likely to be gained, secured or enhanced where there are palpable movements or political parties agitating for independence in these smaller territories. A closer look at the fortunes, operations and dynamics of independence parties from subnational island jurisdictions can offer some interesting insights on the appetite for sovereignty and independence, but also the lack thereof, in the twenty-first century.peer-reviewe

Progress with the Upgrade of the SPS for the HL-LHC Era

The demanding beam performance requirements of the High Luminosity (HL-) LHC project translate into a set of requirements and upgrade paths for the LHC injector complex. In this paper the performance requirements for the SPS and the known limitations are reviewed in the light of the 2012 operational experience. The various SPS upgrades in progress and still under consideration are described, in addition to the machine studies and simulations performed in 2012. The expected machine performance reach is estimated on the basis of the present knowledge, and the remaining decisions that still need to be made concerning upgrade options are detailed.Comment: 3 p. Presented at 4th International Particle Accelerator Conference (IPAC 2013

Aberrant gyrification contributes to the link between gestational age and adult IQ after premature birth

Gyrification is a hallmark of human brain development, starting in the second half of gestation in primary cortices, followed by unimodal and then transmodal associative cortices. Alterations in gyrification have been noted in premature-born newborns and children, suggesting abnormal cortical folding to be a permanent feature of prematurity. Furthermore, both gyrification and prematurity are tightly linked with cognitive performance, indicating a link between prematurity, gyrification, and cognitive performance. To investigate this triangular relation, we tested the following two hypotheses: (i) gyrification is aberrant in premature-born adults; and (ii) aberrant gyrification contributes to the impact of prematurity on adult cognitive performance. One hundred and one very premature-born adults (i.e. adults born before 32 weeks of gestation, and/or with birth weight <1500 g) and 111 mature-born adults were assessed by structural MRI and cognitive testing at 27 years of age. Gyrification was measured by local cortical absolute mean curvature (AMC), evaluated through structural MRI. Cognitive performance was assessed by the Wechsler Adult Intelligence Scale, full-scale IQ test. Two-sample t-tests, regression and mediation analyses were used to assess AMC group differences and the relation between AMC, birth-related variables, and full-scale IQ. Three key findings were identified. First, local AMC was widely increased in fronto-temporo-parietal primary and associative cortices of very premature-born adults. Increase of AMC was inversely associated with gestational age and birth weight and positively associated with medical complications at birth, respectively. Second, increased AMC of temporal associative cortices specifically contributed to the association between prematurity and reduced adult IQ (two-path mediation), indicating that aberrant gyrification of temporal associative cortices is critical for impaired cognitive performance after premature birth. Finally, further investigation of the relationship of gyrification between the early folding postcentral cortices and associative temporal cortices, folding later during neurodevelopment, revealed that the effect of gyrification abnormalities in associative temporal cortices on adult IQ is influenced itself by gyrification abnormalities occurring in the early folding postcentral cortices (three-path mediation). These results indicate that gyrification development across cortical areas in the brain conveys prematurity effects on adult IQ. Overall, these results provide evidence that premature birth leads to permanently aberrant gyrification patterns suggesting an altered neurodevelopmental trajectory. Statistical mediation modelling suggests that both aberrant gyrification itself as well as its propagation across the cortex express aspects of impaired neurodevelopment after premature birth and lead to reduced cognitive performance in adulthood. Thus, markers of gyrification appear as potential candidates for prognosis and treatment of prematurity effects

Reduced apparent fiber density in the white matter of premature-born adults

Premature-born adults exhibit lasting white matter alterations as demonstrated by widespread reduction in fractional anisotropy (FA) based on diffusion-weighted imaging (DWI). FA reduction, however, is non-specific for microscopic underpinnings such as aberrant myelination or fiber density (FD). Using recent advances in DWI, we tested the hypothesis of reduced FD in premature-born adults and investigated its link with the degree of prematurity and cognition. 73 premature- and 89 mature-born adults aged 25–27 years underwent single-shell DWI, from which a FD measure was derived using convex optimization modeling for microstructure informed tractography (COMMIT). Premature-born adults exhibited lower FD in numerous tracts including the corpus callosum and corona radiata compared to mature-born adults. These FD alterations were associated with both the degree of prematurity, as assessed via gestational age and birth weight, as well as with reduced cognition as measured by full-scale IQ. Finally, lower FD overlapped with lower FA, suggesting lower FD underlie unspecific FA reductions. Results provide evidence that premature birth leads to lower FD in adulthood which links with lower full-scale IQ. Data suggest that lower FD partly underpins FA reductions of premature birth but that other processes such as hypomyelination might also take place

Automated quantitative evaluation of brain MRI may be more accurate for discriminating preterm born adults

Objective To investigate the structural brain abnormalities and their diagnostic accuracy through qualitative and quantitative analysis in term born and very preterm birth or with very low birth weight (VP/VLBW) adults. Methods We analyzed 3-T MRIs acquired in 2011–2013 from 67 adults (27 term born controls, mean age 26.4 years, 8 females; 40 VP/VLBWs, mean age 26.6 years, 16 females). We compared automatic segmentations of the white matter, deep gray matter and cortical gray matter, manual corpus callosum measurements and visual ratings of the ventricles and white matter with t tests, logistic regression, and receiver operator characteristic (ROC) curves. Results Automatic segmentation correctly classified 84% of cases; visual ratings correctly classified 63%. Quantitative volumetry based on automatic segmentation revealed higher ventricular volume, lower posterior corpus callosum, and deep gray matter volumes in VP/VLBW subjects compared to controls (p < 0.01). Visual rating and manual measurement revealed a thinner corpus callosum in VP/VLBW adults (p = 0.04) and deformed lateral ventricles (p = 0.03) and tendency towards more “dirty” white matter (p = 0.06). Automatic/manual measures combined with visual ratings correctly classified 87% of cases. Stepwise logistic regression identified three independent features that correctly classify 81% of cases: ventricular volume, deep gray matter volume, and white matter aspect. Conclusion Enlarged and deformed lateral ventricles, thinner corpus callosum, and “dirty” white matter are prevalent in preterm born adults. Their visual evaluation has low diagnostic accuracy. Automatic volume quantification is more accurate but time consuming. It may be useful to ask for prematurity before initiating further diagnostics in subjects with these alterations

Decreased cortical thickness mediates the relationship between premature birth and cognitive performance in adulthood

Cortical thickness (CTh) reflects cortical properties such as dendritic complexity and synaptic density, which are not only vulnerable to developmental disturbances caused by premature birth but also highly relevant for cognitive performance. We tested the hypotheses whether CTh in young adults is altered after premature birth and whether these aberrations are relevant for general cognitive abilities. We investigated CTh based on brain structural magnetic resonance imaging and surface‐based morphometry in a large and prospectively collected cohort of 101 very premature‐born adults (<32 weeks of gestation and/or birth weight [BW] below 1,500 g) and 111 full‐term controls at 26 years of age. Cognitive performance was assessed by full‐scale intelligence quotient (IQ) using the Wechsler Adult Intelligence Scale. CTh was reduced in frontal, parietal, and temporal associative cortices predominantly in the left hemisphere in premature‐born adults compared to controls. We found a significant positive association of CTh with both gestational age and BW, particularly in the left hemisphere, and a significant negative association between CTh and intensity of neonatal treatment within limited regions bilaterally. Full‐scale IQ and CTh in the left hemisphere were positively correlated. Furthermore, CTh in the left hemisphere acted as a mediator on the association between premature birth and full‐scale IQ. Results provide evidence that premature born adults have widespread reduced CTh that is relevant for their general cognitive performance. Data suggest lasting reductions in cortical microstructure subserving CTh after premature birth

Hippocampal subfield volumes are nonspecifically reduced in premature‐born adults

Reduced global hippocampus volumes have been demonstrated in premature‐born individuals, from newborns to adults; however, it is unknown whether hippocampus subfield (HCSF) volumes are differentially affected by premature birth and how relevant they are for cognitive performance. To address these questions, we investigated magnetic resonance imaging (MRI)‐derived HCSF volumes in very premature‐born adults, and related them with general cognitive performance in adulthood. We assessed 103 very premature‐born (gestational age [GA] <32 weeks and/or birth weight <1,500 g) and 109 term‐born individuals with cognitive testing and structural MRI at 26 years of age. HCSFs were automatically segmented based on three‐dimensional T1‐ and T2‐weighted sequences and studied both individually and grouped into three functional units, namely hippocampus proper (HP), subicular complex (SC), and dentate gyrus (DG). Cognitive performance was measured using the Wechsler‐Adult‐Intelligence‐Scale (full‐scale intelligence quotient [FS‐IQ]) at 26 years. We observed bilateral volume reductions for almost all HCSF volumes in premature‐born adults and associations with GA and neonatal treatment intensity but not birth weight. Left‐sided HP, SC, and DG volumes were associated with adult FS‐IQ. Furthermore, left DG volume was a mediator of the association between GA and adult FS‐IQ in premature‐born individuals. Results demonstrate nonspecifically reduced HCSF volumes in premature‐born adults; but specific associations with cognitive outcome highlight the importance of the left DG. Data suggest that specific interventions toward hippocampus function might be promising to lower adverse cognitive effects of prematurity

The LBNO long-baseline oscillation sensitivities with two conventional neutrino beams at different baselines

The proposed Long Baseline Neutrino Observatory (LBNO) initially consists of $\sim 20$ kton liquid double phase TPC complemented by a magnetised iron calorimeter, to be installed at the Pyh\"asalmi mine, at a distance of 2300 km from CERN. The conventional neutrino beam is produced by 400 GeV protons accelerated at the SPS accelerator delivering 700 kW of power. The long baseline provides a unique opportunity to study neutrino flavour oscillations over their 1st and 2nd oscillation maxima exploring the $L/E$ behaviour, and distinguishing effects arising from $\delta_{CP}$ and matter. In this paper we show how this comprehensive physics case can be further enhanced and complemented if a neutrino beam produced at the Protvino IHEP accelerator complex, at a distance of 1160 km, and with modest power of 450 kW is aimed towards the same far detectors. We show that the coupling of two independent sub-MW conventional neutrino and antineutrino beams at different baselines from CERN and Protvino will allow to measure CP violation in the leptonic sector at a confidence level of at least $3\sigma$ for 50\% of the true values of $\delta_{CP}$ with a 20 kton detector. With a far detector of 70 kton, the combination allows a $3\sigma$ sensitivity for 75\% of the true values of $\delta_{CP}$ after 10 years of running. Running two independent neutrino beams, each at a power below 1 MW, is more within today's state of the art than the long-term operation of a new single high-energy multi-MW facility, which has several technical challenges and will likely require a learning curve.Comment: 21 pages, 12 figure