Uptake of fetal aneuploidy screening after the introduction of the non-invasive prenatal test: A national population-based register study.

INTRODUCTION: The introduction of the non-invasive prenatal test (NIPT) has shifted the prenatal screening landscape. Countries are exploring ways to integrate NIPT in their national prenatal screening programs, either as a first- or second-tier test. This study aimed to describe how the uptake of fetal aneuploidy screening changed after the introduction of NIPT as a second-tier and as a first-tier test within the national prenatal screening program of the Netherlands. MATERIAL AND METHODS: A population-based register study in the Netherlands, recording uptake of fetal aneuploidy screening. Data from all pregnant women choosing to have the first-trimester combined test (FCT) or first-tier NIPT between January 2007 and March 2019 were retrospectively collected using national registration systems. Uptake percentages for fetal aneuploidy screening (FCT and NIPT) were calculated and stratified by region and maternal age. Statistical significance was determined using trend analysis and chi-squared tests. RESULTS: Between 2007 and 2013 FCT uptake increased from 14.8% to 29.5% (P = .004). In April 2014 NIPT was introduced as a second-tier test for high-risk women after FCT (TRIDENT-1 study). FCT uptake rose from 29.5% in 2013 to 34.2% in 2015 (P < .0001). After the introduction of NIPT as a first-tier test for all women in April 2017 (TRIDENT-2 study), FCT uptake declined significantly from 35.8% in 2016 to 2.6% in 2018 (P < .0001). NIPT uptake increased to 43.4% in 2018. Regionally, NIPT uptake ranged from 31.8% to 67.9%. Total uptake (FCT and NIPT) between 2007 and 2018 increased significantly from 14.8% to 45.9% (P < .0001). However, total uptake stabilized at 46% for both years of TRIDENT-2 (April 2017-March 2019). CONCLUSIONS: An increase in total fetal aneuploidy screening uptake up to 45.9% was observed after the introduction of NIPT. Uptake appears to have stabilized within a year after introducing first-tier NIPT.

Oscillatory brain activity associates with neuroligin-3 expression and predicts progression free survival in patients with diffuse glioma.

INTRODUCTION: Diffuse gliomas have local and global effects on neurophysiological brain functioning, which are often seen as 'passive' consequences of the tumor. However, seminal preclinical work has shown a prominent role for neuronal activity in glioma growth: mediated by neuroligin-3 (NLGN3), increased neuronal activity causes faster glioma growth. It is unclear whether the same holds true in patients. Here, we investigate whether lower levels of oscillatory brain activity relate to lower NLGN3 expression and predict longer progression free survival (PFS) in diffuse glioma patients. METHODS: Twenty-four newly diagnosed patients with diffuse glioma underwent magnetoencephalography and subsequent tumor resection. Oscillatory brain activity was approximated by calculating broadband power (0.5-48 Hz) of the magnetoencephalography. NLGN3 expression in glioma tissue was semi-quantitatively assessed by immunohistochemistry. Peritumor and global oscillatory brain activity was then compared between different levels of NLGN3 expression with Kruskal-Wallis tests. Cox proportional hazards analyses were performed to estimate the predictive value of oscillatory brain activity for PFS. RESULTS: Patients with low expression of NLGN3 had lower levels of global oscillatory brain activity than patients with higher NLGN3 expression (P < 0.001). Moreover, lower peritumor (hazard ratio 2.17, P = 0.008) and global oscillatory brain activity (hazard ratio 2.10, P = 0.008) predicted longer PFS. CONCLUSIONS: Lower levels of peritumor and global oscillatory brain activity are related to lower NLGN3 expression and longer PFS, corroborating preclinical research. This study highlights the important interplay between macroscopically measured brain activity and glioma progression, and may lead to new therapeutic interventions in diffuse glioma patients.

Dynamic hub load predicts cognitive decline after resective neurosurgery.

Resective neurosurgery carries the risk of postoperative cognitive deterioration. The concept of 'hub (over)load', caused by (over)use of the most important brain regions, has been theoretically postulated in relation to symptomatology and neurological disease course, but lacks experimental confirmation. We investigated functional hub load and postsurgical cognitive deterioration in patients undergoing lesion resection. Patients (n = 28) underwent resting-state magnetoencephalography and neuropsychological assessments preoperatively and 1-year after lesion resection. We calculated stationary hub load score (SHub) indicating to what extent brain regions linked different subsystems; high SHub indicates larger processing pressure on hub regions. Dynamic hub load score (DHub) assessed its variability over time; low values, particularly in combination with high SHub values, indicate increased load, because of consistently high usage of hub regions. Hypothetically, increased SHub and decreased DHub relate to hub overload and thus poorer/deteriorating cognition. Between time points, deteriorating verbal memory performance correlated with decreasing upper alpha DHub. Moreover, preoperatively low DHub values accurately predicted declining verbal memory performance. In summary, dynamic hub load relates to cognitive functioning in patients undergoing lesion resection: postoperative cognitive decline can be tracked and even predicted using dynamic hub load, suggesting it may be used as a prognostic marker for tailored treatment planning.

Direction of information flow in large-scale resting-state networks is frequency-dependent.

Normal brain function requires interactions between spatially separated, and functionally specialized, macroscopic regions, yet the directionality of these interactions in large-scale functional networks is unknown. Magnetoencephalography was used to determine the directionality of these interactions, where directionality was inferred from time series of beamformer-reconstructed estimates of neuronal activation, using a recently proposed measure of phase transfer entropy. We observed well-organized posterior-to-anterior patterns of information flow in the higher-frequency bands (alpha1, alpha2, and beta band), dominated by regions in the visual cortex and posterior default mode network. Opposite patterns of anterior-to-posterior flow were found in the theta band, involving mainly regions in the frontal lobe that were sending information to a more distributed network. Many strong information senders in the theta band were also frequent receivers in the alpha2 band, and vice versa. Our results provide evidence that large-scale resting-state patterns of information flow in the human brain form frequency-dependent reentry loops that are dominated by flow from parieto-occipital cortex to integrative frontal areas in the higher-frequency bands, which is mirrored by a theta band anterior-to-posterior flow.