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Background: Being able to differentiate mild cognitive impairment (MCI) patients who would eventually convert (MCIc) to Alzheimer's disease (AD) from those who would not (MCInc) is a key challenge for prognosis., Objective: This study aimed to investigate the ability of sulcal morphometry to predict MCI progression to AD, dedicating special attention to an accurate identification of sulci., Methods: Twenty-five AD patients, thirty-seven MCI and twenty-five healthy controls (HC) underwent a brain-MR protocol (1.5T scanner) including a high-resolution T1-weighted sequence. MCI patients underwent a neuropsychological assessment at baseline and were clinically re-evaluated after a mean of 2.3 years. At follow-up, 12 MCI were classified as MCInc and 25 as MCIc. Sulcal morphometry was investigated using the BrainVISA framework. Consistency of sulci across subjects was ensured by visual inspection and manual correction of the automatic labelling in each subject. Sulcal surface, depth, length, and width were retrieved from 106 sulci. Features were compared across groups and their classification accuracy in predicting MCI conversion was tested. Potential relationships between sulcal features and cognitive scores were explored using Spearman's correlation., Results: The width of sulci in the temporo-occipital region strongly differentiated between each pair of groups. Comparing MCIc and MCInc, the width of several sulci in the bilateral temporo-occipital and left frontal areas was significantly altered. Higher width of frontal sulci was associated with worse performances in short-term verbal memory and phonemic fluency., Conclusions: Sulcal morphometry emerged as a strong tool for differentiating HC, MCI, and AD, demonstrating its potential prognostic value for the MCI population.

Automatic neuroimaging processing tools provide convenient and systematic methods for extracting features from brain magnetic resonance imaging scans. One tool, FreeSurfer, provides an easy-to-use pipeline to extract cortical and subcortical morphometric measures. There have been over 25 stable releases of FreeSurfer, with different versions used across published works. The reliability and compatibility of regional morphometric metrics derived from the most recent version releases have yet to be empirically assessed. Here, we used test-retest data from three public data sets to determine within-version reliability and between-version compatibility across 42 regional outputs from FreeSurfer versions 7.1, 6.0, and 5.3. Cortical thickness from v7.1 was less compatible with that of older versions, particularly along the cingulate gyrus, where the lowest version compatibility was observed (intraclass correlation coefficient 0.37-0.61). Surface area of the temporal pole, frontal pole, and medial orbitofrontal cortex, also showed low to moderate version compatibility. We confirm low compatibility between v6.0 and v5.3 of pallidum and putamen volumes, while those from v7.1 were compatible with v6.0. Replication in an independent sample showed largely similar results for measures of surface area and subcortical volumes, but had lower overall regional thickness reliability and compatibility. Batch effect correction may adjust for some inter-version effects when most sites are run with one version, but results vary when more sites are run with different versions. Age associations in a quality controlled independent sample (N = 106) revealed version differences in results of downstream statistical analysis. We provide a reference to highlight the regional metrics that may yield recent version-related inconsistencies in published findings. An interactive viewer is provided at http://data.brainescience.org/Freesurfer_Reliability/., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Objective: To define for women at low obstetric risk methods of management that respect the rhythm and the spontaneous course of giving birth as well as each woman's preferences., Methods: These clinical practice guidelines were developed through professional consensus based on an analysis of the literature and of the French and international guidelines available on this topic., Results: Labor should be monitored with a partograph (professional consensus). Digital cervical examination should be offered every 4 h during the first stage of labor, hourly during the second. The choice between continuous (cardiotocography) or discontinuous (by cardiotocography or intermittent auscultation) monitoring should be left to the woman (professional consensus). In the active phase of the first stage of labor, dilation speed is considered abnormal if it is less than 1 cm/4 h between 5 and 7 cm or less than 1 cm/2 h after 7 cm. In those cases, an amniotomy is recommended if the membranes are intact, and the administration of oxytocin if the membranes are already broken and uterine contractions are judged insufficient (professional consensus). It is recommended that pushing not begin when full dilation has been reached; rather, the fetus should be allowed to descend (grade A). Umbilical cord clamping should be delayed beyond the first 30 s in newborns who do not require resuscitation (grade C)., Conclusion: The establishment of these clinical practice guidelines should enable women at low obstetric risk to receive better care in conditions of optimal safety while supporting physiologic birth.

Genetic associations with macroscopic brain structure can provide insights into brain function and disease. However, specific associations with measures of local brain folding are largely under-explored. Here, we conducted large-scale genome- and exome-wide associations of regional cortical sulcal measures derived from magnetic resonance imaging scans of 40,169 individuals in UK Biobank. We discovered 388 regional brain folding associations across 77 genetic loci, with genes in associated loci enriched for expression in the cerebral cortex, neuronal development processes, and differential regulation during early brain development. We integrated brain eQTLs to refine genes for various loci, implicated several genes involved in neurodevelopmental disorders, and highlighted global genetic correlations with neuropsychiatric phenotypes. We provide an interactive 3D visualisation of our summary associations, emphasising added resolution of regional analyses. Our results offer new insights into the genetic architecture of brain folding and provide a resource for future studies of sulcal morphology in health and disease., (© 2022. The Author(s).)

We conducted a systematic review and meta-analysis of 30 functional magnetic resonance imaging studies investigating processing of musical rhythms in neurotypical adults. First, we identified a general network for musical rhythm, encompassing all relevant sensory and motor processes (Beat-based, rest baseline, 12 contrasts) which revealed a large network involving auditory and motor regions. This network included the bilateral superior temporal cortices, supplementary motor area (SMA), putamen, and cerebellum. Second, we identified more precise loci for beat-based musical rhythms (Beat-based, audio-motor control, 8 contrasts) in the bilateral putamen. Third, we identified regions modulated by beat based rhythmic complexity (Complexity, 16 contrasts) which included the bilateral SMA-proper/pre-SMA, cerebellum, inferior parietal regions, and right temporal areas. This meta-analysis suggests that musical rhythm is largely represented in a bilateral cortico-subcortical network. Our findings align with existing theoretical frameworks about auditory-motor coupling to a musical beat and provide a foundation for studying how the neural bases of musical rhythm may overlap with other cognitive domains., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Here we review the motivation for creating the enhancing neuroimaging genetics through meta-analysis (ENIGMA) Consortium and the genetic analyses undertaken by the consortium so far. We discuss the methodological challenges, findings, and future directions of the genetics working group. A major goal of the working group is tackling the reproducibility crisis affecting "candidate gene" and genome-wide association analyses in neuroimaging. To address this, we developed harmonized analytic methods, and support their use in coordinated analyses across sites worldwide, which also makes it possible to understand heterogeneity in results across sites. These efforts have resulted in the identification of hundreds of common genomic loci robustly associated with brain structure. We have found both pleiotropic and specific genetic effects associated with brain structures, as well as genetic correlations with psychiatric and neurological diseases., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Anorexia nervosa (AN) is a difficult to treat, pernicious psychiatric disorder that has been linked to decision-making abnormalities. We examined the structural characteristics of habitual and goal-directed decision-making circuits and their connecting white matter tracts in 32 AN and 43 healthy controls across two independent data sets of adults and adolescents as an explanatory sub-study. Total bilateral premotor/supplementary motor area-putamen tracts in the habit circuit had a significantly higher volume in adults with AN, relative to controls. Positive correlations were found between both the number of tracts and white matter volume (WMV) in the habit circuit, and the severity of ritualistic/compulsive behaviors in adults and adolescents with AN. Moreover, we found a significant influence of the habit circuit WMV on AN ritualistic/compulsive symptom severity, depending on the preoccupations symptom severity levels. These findings suggest that AN is associated with white matter plasticity alterations in the habit circuit. The association between characteristics of habit circuit white matter tracts and AN behavioral symptoms provides support for a circuit based neurobiological model of AN, and identifies the habit circuit as a focus for further investigation to aid in development of novel and more effective treatments based on brain-behavior relationships., (© 2021. The Author(s).)

An accurate measure of the complexity of patterns of cortical folding or gyrification is necessary for understanding normal brain development and neurodevelopmental disorders. Conventional gyrification indices (GIs) are calculated based on surface curvature (curvature-based GI) or an outer hull surface of the cortex (outer surface-based GI). The latter is dependent on the definition of the outer hull surface and a corresponding function between surfaces. In the present study, we propose the Laplace Beltrami-based gyrification index (LB-GI). This is a new curvature-based local GI computed using the first three Laplace Beltrami eigenfunction level sets. As with outer surface-based GI methods, this method is based on the hypothesis that gyrification stems from a flat surface during development. However, instead of quantifying gyrification with reference to corresponding points on an outer hull surface, LB-GI quantifies the gyrification at each point on the cortical surface with reference to their surrounding gyral points, overcoming several shortcomings of existing methods. The LB-GI was applied to investigate the cortical maturation profile of the human brain from preschool to early adulthood using the PING database. The results revealed more detail in patterns of cortical folding than conventional curvature-based methods, especially on frontal and posterior tips of the brain, such as the frontal pole, lateral occipital, lateral cuneus, and lingual. Negative associations of cortical folding with age were observed at cortical regions, including bilateral lingual, lateral occipital, precentral gyrus, postcentral gyrus, and superior frontal gyrus. The results also indicated positive significant associations between age and the LB-GI of bilateral insula, the medial orbitofrontal, frontal pole and rostral anterior cingulate regions. It is anticipated that the LB-GI will be advantageous in providing further insights in the understanding of brain development and degeneration in large clinical neuroimaging studies., (Copyright © 2021. Published by Elsevier Inc.)

Magnetic resonance imaging (MRI) has a potential for early diagnosis of individuals at risk for developing Alzheimer's disease (AD). Cognitive performance in healthy elderly people and in those with mild cognitive impairment (MCI) has been associated with measures of cortical gyrification [1] and thickness (CT) [2], yet the extent to which sulcal measures can help to predict AD conversion above and beyond CT measures is not known. Here, we analyzed 721 participants with MCI from phases 1 and 2 of the Alzheimer's Disease Neuroimaging Initiative, applying a two-state Markov model to study the conversion from MCI to AD condition. Our preliminary results suggest that MRI-based cortical features, including sulcal morphometry, may help to predict conversion from MCI to AD.

Objective: The objective of these guidelines is to define for women at low obstetric risk modalities that respect the physiology of delivery and guarantee the quality and safety of maternal and newborn care., Methods: These guidelines were made by a consensus of experts based on an analysis of the scientific literature and the French and international recommendations available on the subject., Results: It is recommended to conduct a complete initial examination of the woman in labor at admission (consensus agreement). The labor will be monitored using a partogram that is a useful traceability tool (consensus agreement). A transvaginal examination may be offered every two to four hours during the first stage of labor and every hour during the second stage of labor or before if the patient requests it, or in case of a warning sign. It is recommended that if anesthesia is required, epidural or spinal anesthesia should be used to prevent bronchial inhalation (grade A). The consumption of clear fluids is permitted throughout labor in patients with a low risk of general anesthesia (grade B). It is recommended to carry out a "low dose" epidural analgesia that respects the experience of delivery (grade A). It is recommended to maintain the epidural analgesia through a woman's self-administration pump (grade A). It is recommended to give the woman the choice of continuous (by cardiotocography) or discontinuous (by cardiotocography or intermittent auscultation) monitoring if the conditions of maternity organization and the permanent availability of staff allow it and, after having informed the woman of the benefits and risks of each technique (consensus agreement). In the active phase of the first stage of labor, the dilation rate is considered abnormal if it is less than 1cm/4h between 5 and 7cm or less than 1cm/2h above 7cm (level of Evidence 2). It is then recommended to propose an amniotomy if the membranes are intact or an oxytocin administration if the membranes are already ruptured, and the uterine contractions considered insufficient (consensus agreement). It is recommended not to start expulsive efforts as soon as complete dilation is identified, but to let the presentation of the fetus drop (grade A). It is recommended to inform the gynecologist-obstetrician in case of nonprogression of the fetus after two hours of complete dilation with sufficient uterine dynamics (consensus agreement). It is recommended not to use abdominal expression (grade B). It is recommended to carry out preventive administration of oxytocin at 5 or 10 IU to prevent PPH after vaginal delivery (grade A). In the case of placental retention, it is recommended to perform a manual removal of the placenta (grade A). In the absence of bleeding, it should be performed 30minutes but not more than 60minutes after delivery (consensus agreement). It is recommended to assess at birth the breathing or screaming, and tone of the newborn to quickly determine if resuscitation is required (consensus agreement). If the parameters are satisfactory (breathing present, screaming frankly, and normal tonicity), it is recommended to propose to the mother that she immediately place the newborn skin-to-skin with her mother if she wishes, with a monitoring protocol (grade B). Delayed cord clamping is recommended beyond the first 30seconds in neonates, not requiring resuscitation (grade C). It is recommended that the first oral dose (2mg) of vitamin K (consensus agreement) be given systematically within two hours of birth., Conclusion: These guidelines allow women at low obstetric risk to benefit from a better quality of care and optimal safety conditions while respecting the physiology of delivery., (Copyright © 2020. Published by Elsevier Masson SAS.)

Objective: To assess maternal postures during the second stage of labour on course of labour, mode of delivery and maternal and neonatal morbidity. To describe the different techniques of spontaneous vaginal delivery and their influence on maternal and neonatal morbidity. To describe the different perineal protection techniques., Method: Systematic review of the literature through consultation of Medline, Cochrane databases and international recommendations., Results: There is no particular posture that has demonstrated its superiority (Level of Evidence (LE) 2). In case of no contraindication and permanent maternal and fetal monitoring, it is recommended to encourage women to adopt the postures they consider most comfortable during the second stage of labour (Consensus agreement). There is insufficient evidence in the literature to recommend a technique for fetal head and shoulders delivery. There is not enough data in the literature to recommend the use of Ritgen maneuver (grade B), perineal massage (gradeC) or hot compresses (Consensus agreement). The abdominal expression must be abandoned (grade B)., Conclusion: The second stage of labour is a crucial time in labour that can lead to significant maternal and neonatal morbidity. It is necessary to take the greatest possible care in the supervision and management of women, especially for the perineal protection. The influence of non-medicinal techniques on the course of the second stage of labour should be studied., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.

Cortical folds help drive the parcellation of the human cortex into functionally specific regions. Variations in the length, depth, width, and surface area of these sulcal landmarks have been associated with disease, and may be genetically mediated. Before estimating the heritability of sulcal variation, the extent to which these metrics can be reliably extracted from in-vivo MRI must be established. Using four independent test-retest datasets, we found high reliability across the brain (intraclass correlation interquartile range: 0.65-0.85). Heritability estimates were derived for three family-based cohorts using variance components analysis and pooled (total N > 3000); the overall sulcal heritability pattern was correlated to that derived for a large population cohort (N > 9000) calculated using genomic complex trait analysis. Overall, sulcal width was the most heritable metric, and earlier forming sulci showed higher heritability. The inter-hemispheric genetic correlations were high, yet select sulci showed incomplete pleiotropy, suggesting hemisphere-specific genetic influences.

DS-1040, a novel low-molecular-weight inhibitor of activated thrombin-activatable fibrinolysis inhibitor, is under development for the treatment of thromboembolic diseases including venous thromboembolism and acute ischemic stroke. Here we describe the results of 3 studies that evaluated the safety and tolerability of DS-1040 along with the effect on DS-1040 pharmacokinetic (PK) parameters, when dosed alone or when coadministered with aspirin (NCT02071004), clopidogrel (NCT02560688), or enoxaparin in healthy subjects. Concomitant administration of single-dose DS-1040 with multiple-dose aspirin, multiple-dose clopidogrel, or single-dose enoxaparin, consistent with clinically relevant dose regimens, was safe and well tolerated with no serious treatment-emergent adverse events (TEAEs), TEAEs leading to discontinuation, bleeding-related TEAEs, and no significant changes in coagulation parameters. DS-1040 did not prolong bleeding time when administered concomitantly with aspirin or clopidogrel. In the aspirin study, DS-1040 PK was evaluated following the concomitant administration with multiple-dose aspirin, where the plasma DS-1040 exposure (peak plasma concentration [C max ] and area under the concentration-time curve [AUC inf ]) was to be similar to the data previously published in the first-in-human study of DS-1040 in healthy subjects. The PK parameters of DS-1040 coadministered with clopidogrel were similar to those of DS-1040 alone, with small increases in geometric means for C max (7%) and AUC last (9%). When coadministered with enoxaparin, the PK parameters of DS-1040 were not affected (1.1% and 1.5% decreases in geometric means for C max and AUC last , respectively). Therefore, concomitant administration of DS-1040 and clopidogrel or enoxaparin did not demonstrate PK drug-drug interactions., (© 2020, The American College of Clinical Pharmacology.)

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)