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The ability to attribute mental states to other individuals is crucial for human cognition. A milestone of this ability is reached around the age of 4, when children start understanding that others can have false beliefs about the world. The neural basis supporting this critical step is currently unknown. Here, we relate this behavioural change to the maturation of white matter structure in 3- and 4-year-old children. Tract-based spatial statistics and probabilistic tractography show that the developmental breakthrough in false belief understanding is associated with age-related changes in local white matter structure in temporoparietal regions, the precuneus and medial prefrontal cortex, and with increased dorsal white matter connectivity between temporoparietal and inferior frontal regions. These effects are independent of co-developing cognitive abilities. Our findings show that the emergence of mental state representation is related to the maturation of core belief processing regions and their connection to the prefrontal cortex. At age 4, children start understanding other peoples' false beliefs, but the related neuroanatomical changes are unknown. Here, authors show that false belief understanding is associated with age-related changes in white matter structure, and that this effect is independent of other cognitive abilities.

Diffusion MRI (dMRI) measurements are used for inferring the microstructural properties of white matter and to reconstruct fiber pathways. Very often voxels contain complex fiber configurations comprising multiple bundles, rendering the simple diffusion tensor model unsuitable. Multi-compartment models deliver a convenient parameterization of the underlying complex fiber architecture, but pose challenges for fitting and model selection. Spherical deconvolution, in contrast, very economically produces a fiber orientation density function (fODF) without any explicit model assumptions. Since, however, the fODF is represented by spherical harmonics, a direct interpretation of the model parameters is impossible. Based on the fact that the fODF can often be interpreted as superposition of multiple peaks, each associated to one relatively coherent fiber population (bundle), we offer a solution that seeks to combine the advantages of both approaches: first the fiber configuration is modeled as fODF represented by spherical harmonics and then each of the peaks is parameterized separately in order to characterize the underlying bundle. In this work, the fODF peaks are approximated by Bingham distributions, capturing first and second-order statistics of the fiber orientations, from which we derive metrics for the parametric quantification of fiber bundles. We propose meaningful relationships between these measures and the underlying microstructural properties. We focus on metrics derived directly from properties of the Bingham distribution, such as peak length, peak direction, peak spread, integral over the peak, as well as a metric derived from the comparison of the largest peaks, which probes the complexity of the underlying microstructure. We compare these metrics to the conventionally used fractional anisotropy (FA) and show how they may help to increase the specificity of the characterization of microstructural properties. While metrics relying on the first moments of the Bingham distributions provide relatively robust results, second-order metrics representing the peak spread are only meaningful, if the SNR is very high and no fiber crossings are present in the voxel.

Modern approaches to investigate complex brain dynamics suggest to represent the brain as a functional network of brain regions defined by a brain atlas, while edges represent the structural or functional connectivity among them. This approach is also utilized for mathematical modeling of the resting-state brain dynamics, where the applied brain parcellation plays an essential role in deriving the model network and governing the modeling results. There is however no consensus and empirical evidence on how a given brain atlas affects the model outcome, and the choice of parcellation is still rather arbitrary. Accordingly, we explore the impact of brain parcellation on inter-subject and inter-parcellation variability of model fitting to empirical data. Our objective is to provide a comprehensive empirical evidence of potential influences of parcellation choice on resting-state whole-brain dynamical modeling. We show that brain atlases strongly influence the quality of model validation and propose several variables calculated from empirical data to account for the observed variability. A few classes of such data variables can be distinguished depending on their inter-subject and inter-parcellation explanatory power.

An ideal induction drug for cesarean section (CS) must have quick action, with minimum side effects such as awareness, hemodynamic compromise, and neonatal depression. Thiopentone is frequently used; however, no reliable evidence is available to support its use as a dedicated hypnotic agent in this setting. A systematic review and meta-analysis, using PRISMA methodology, of randomized controlled trials (RCTs), comparing women undergoing CS using thiopentone with those undergoing CS with propofol, ketamine, or benzodiazepines as hypnotic agents. Comprehensive search without language restrictions of MEDLINE, EMBASE, and the Cochrane Controlled Trials Registers until May 2015, with an update in January 2017. Included trials must have reported at least one of the following variables: neonatal arterial or venous umbilical blood gas, maternal systolic blood pressure pre- and post-intubation, or Apgar score. A total of 911 patients from 18 RCTs were eligible for quantitative analysis. The increase in maternal systolic blood pressure was smaller in patients administered propofol, compared with those administered thiopentone (weighted mean difference [WMD]: −11.52 [−17.60, −5.45]; p = 0.0002). Induction with propofol also resulted in a significantly lower umbilical arterial pO2 (WMD: −0.12 [−0.20, −0.04]; p = 0.004) than induction with thiopentone. A comparison between propofol and thiopentone revealed no significant differences in other umbilical blood gas parameters or in Apgar scores. In contrast, when comparing ketamine with thiopentone, the number of neonates with a lower Apgar score (<7) at 1 and 5 min was significantly higher in the ketamine group than in the thiopentone group (p = 0.004). The evidence, based on sparse and relatively old trials, indicates that propofol and thiopentone are equally suited for CS. After 1 and 5 min, ketamine yields lower Apgar scores than thiopentone. Additional well-designed trials are needed to reach firmer conclusions. •Propofol and Thiopentone are equally suited for the induction of cesarean section.•Ketamin for induction in cesarean section patients may initially cause lower Apgar scores.•In general, the evidence is sparse and consists of older trials with weak methodology.

Sleep complaints are the most prevalent syndromes in older adults, particularly in women. Moreover, they are frequently accompanied with a high level of depression and stress. Although several diffusion tensor imaging (DTI) studies reported associations between sleep quality and brain white matter (WM) microstructure, it is still unclear whether gender impacts the effect of sleep quality on structural alterations, and whether these alterations mediate the effects of sleep quality on emotional regulation. We included 389 older participants (176 females, age = 65.5 ± 5.5 years) from the 1000BRAINS project. Neuropsychological examinations covered the assessments of sleep quality, depressive symptomatology, current stress level, visual working memory, and selective attention ability. Based on the DTI dataset, the diffusion parameter maps, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), were calculated and normalized to a population-specific FA template. According to the global Pittsburgh Sleep Quality Index (PSQI), 119 poor sleepers (PSQI: 10~17) and 120 good sleepers (PSQI: 3~6) were identified. We conducted a two by two (good sleepers/poor sleepers) * (males/females) analysis of variance by using tract-based spatial statistics (TBSS) and JHU-ICBM WM atlas-based comparisons. Moreover, we performed a voxel-wise correlation analysis of brain WM microstructure with the neuropsychological tests. Finally, we applied a mediation analysis to explore if the brain WM microstructure mediates the relationship between sleep quality and emotional regulation. No significant differences in brain WM microstructure were detected on the main effect of sleep quality. However, the MD, AD, and RD of pontine crossing tract and bilateral inferior cerebellar peduncle were significant lower in the males than females. Voxel-wise correlation analysis revealed that FA and RD values in the corpus callosum were positively related with depressive symptomatology and negatively related with current stress levels. Additionally, we found a significantly positive association between higher FA values in visual-related WM tracts and better outcomes in a visual pattern recognition test. Furthermore, a mediation analysis suggested that diffusion metrics within the corpus callosum partially mediated the associations between poor sleep quality/high stress and depressive symptomatology.

Diffusion MRI is a non-invasive method that potentially gives insight into the brain's white matter structure regarding the pathway of connections and properties of the axons. Here, we propose a novel global tractography method named Plausibility Tracking that provides the most plausible pathway, modeled as a smooth spline curve, between two locations in the brain. Compared to other tractography methods, plausibility tracking combines the more complete connectivity pattern of probabilistic tractography with smooth tracks that are globally optimized using the fiber orientation density function and hence is relatively robust against local noise and error propagation. It has been tested on phantom and biological data and compared to other methods of tractography. Plausibility tracking provides reliable local directions all along the fiber pathways which makes it especially interesting for tract-based analysis in combination with direction dependent indices of diffusion MRI. In order to demonstrate this potential of plausibility tracking, we propose a framework for the assessment and comparison of diffusion derived tissue properties. This framework comprises atlas-guided parameterization of tract representation and advanced bundle-specific indices describing fiber density, fiber spread and white matter complexity. We explore the new method using real data and show that it allows for a more specific interpretation of the white matter's microstructure compared to rotationally invariant indices derived from the diffusion tensor. •Framework to compare bundle specific parameters derived from dMRI across subjects•Introduction of a new global tractography method called “Plausibility Tracking”•Fast and reliable initialization through probabilistic tractography•More specific results compared to analysis with indices of diffusion tensor

Recent studies suggest that neurobiological anomalies are already detectable in pre-school children with a family history of developmental dyslexia (DD). However, there is a lack of longitudinal studies showing a direct link between those differences at a preliterate age and the subsequent literacy difficulties seen in school. It is also not clear whether the prediction of DD in pre-school children can be significantly improved when considering neurobiological predictors, compared to models based on behavioral literacy precursors only. We recruited 53 pre-reading children either with (N=25) or without a family risk of DD (N=28). Quantitative T1 MNI data and literacy precursor abilities were assessed at kindergarten age. A subsample of 35 children was tested for literacy skills either one or two years later, that is, either in first or second grade. The group comparison of quantitative T1 measures revealed significantly higher T1 intensities in the left anterior arcuate fascicle (AF), suggesting reduced myelin concentration in preliterate children at risk of DD. A logistic regression showed that DD can be predicted significantly better (p=.024) when neuroanatomical differences between groups are used as predictors (80%) compared to a model based on behavioral predictors only (63%). The Wald statistic confirmed that the T1 intensity of the left AF is a statistically significant predictor of DD (p<.05). Our longitudinal results provide evidence for the hypothesis that neuroanatomical anomalies in children with a family risk of DD are related to subsequent problems in acquiring literacy. Particularly, solid white matter organization in the left anterior arcuate fascicle seems to play a pivotal role.

Abstract Background: Bronchoscopic lung volume reduction (BLVR) using 1-way endobronchial valves (EBV) has become a guideline treatment in patients with advanced emphysema. Evidence from this minimally invasive treatment derives mainly from well-designed controlled trials conducted in high-volume specialized intervention centres. Little is known about real-life outcome data in hospitals setting up this novel treatment and which favourable conditions are required for a continuous successful program. Objectives: In this study, we aim to evaluate the eligibility rate for BLVR and whether the implementation of BLVR in our academic hospital is feasible and yields clinically significant outcomes. Method: A retrospective evaluation of patients treated with EBV between January 2016 and August 2019 was conducted. COPD assessment test (CAT), forced expiratory volume in 1 s (FEV1), residual volume (RV), and 6-min walking test (6MWT) were measured at baseline and 3 months after intervention. Paired sample t tests were performed to compare means before and after intervention. Results: Of 350 subjects screened, 283 (81%) were not suitable for intervention mostly due to lack of a target lobe. The remaining 67 subjects (19%) underwent bronchoscopic assessment, and if suitable, valves were placed in the same session. In total, 55 subjects (16%) were treated with EBV of which 10 did not have complete follow-up: 6 subjects had their valves removed because of severe pneumothorax (n = 2) or lack of benefit (n = 4) and the remaining 4 had missing follow-up data. Finally, 45 patients had complete follow-up at 3 months and showed an average change ± SD in CAT −4 ± 6 points, FEV1 +190 ± 140 mL, RV −770 ± 790 mL, and +37 ± 65 m on the 6MWT (all p < 0.001). After 1-year follow-up, 34 (76%) subjects had their EBV in situ. Conclusion: Implementing BLVR with EBV is feasible and effective. Only 16% of screened patients were eligible, indicating that this intervention is only applicable in a small subset of highly selected subjects with advanced emphysema, and therefore a high volume of COPD patients is essential for a sustainable BLVR program.

Factor XII (FXII) deficiency is a congenital disorder inherited as an autosomal recessive condition. In his heterozygous form, it is relatively common in the general population. However, a total absence of FXII as seen in homozygous patients, is rare, with an incidence of approximately 1/1,000,000 individuals. Surprisingly, FXII deficiency is rather associated with thromboembolic complications. Patients do not experience a higher risk of surgical bleeding despite a markedly prolonged activated partial thromboplastin time. Given its low incidence in the general population, the finding of an unknown FXII deficiency is rare during cardiac surgery. This unique case describes a patient with an unanticipated prolonged baseline activated clotting time (ACT) during cardiac surgery in which his bleeding history and rotational thromboelastometry tracings lead us to the diagnosis of a FXII deficiency. The finding of a hypocoagulable INTEM tracing and a concurrent normal EXTEM tracing in a sample of a patient with prolonged ACT and adverse anamnestic bleeding history should prompt clinicians to consider a FXII deficiency. It may help clinicians in further perioperative management where there is not enough time to wait for the results of individual coagulation factor testing.

The high spatial resolution of 7T MRI enables us to identify subtle volume changes in brain structures, providing potential biomarkers of mental disorders. Most volumetric approaches require that similar intensity values represent similar tissue types across different persons. By applying colour-coding to T1-weighted MP2RAGE images, we found that the high measurement accuracy achieved by high-resolution imaging may be compromised by inter-individual variations in the image intensity. To address this issue, we analysed the performance of five intensity standardisation techniques in high-resolution T1-weighted MP2RAGE images. Twenty images with extreme intensities in the GM and WM were standardised to a representative reference image. We performed a multi-level evaluation with a focus on the hypothalamic region-analysing the intensity histograms as well as the actual MR images, and requiring that the correlation between the whole-brain tissue volumes and subject age be preserved during standardisation. The results were compared with T1 maps. Linear standardisation using subcortical ROIs of GM and WM provided good results for all evaluation criteria: it improved the histogram alignment within the ROIs and the average image intensity within the ROIs and the whole-brain GM and WM areas. This method reduced the inter-individual intensity variation of the hypothalamic boundary by more than half, outperforming all other methods, and kept the original correlation between the GM volume and subject age intact. Mixed results were obtained for the other four methods, which sometimes came at the expense of unwarranted changes in the age-related pattern of the GM volume. The mapping of the T1 relaxation time with the MP2RAGE sequence is advertised as being especially robust to bias field inhomogeneity. We found little evidence that substantiated the T1 map's theoretical superiority over the T1-weighted images regarding the inter-individual image intensity homogeneity.