A transdiagnostic examination of cognitive heterogeneity in children and adolescents with neurodevelopmental disorders.

Children and adolescents with neurodevelopmental disorders demonstrate extensive cognitive heterogeneity that is not adequately captured by traditional diagnostic systems, emphasizing the need for alternative assessment and classification techniques. Using a transdiagnostic approach, a retrospective cohort study of cognitive functioning was conducted using a large heterogenous sample (n = 1529) of children and adolescents 7 to 18 years of age with neurodevelopmental disorders. Measures of short-term memory, verbal ability, and reasoning were administered to participants with attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), comorbid ADHD/ASD, and participants without neurodevelopmental disorders (non-NDD) using a 12-task, web-based neurocognitive testing battery. Unsupervised machine learning techniques were used to create a self-organizing map, an artificial neural network, in conjunction with k-means clustering to identify data-driven subgroups. The study aims were to: 1) identify cognitive profiles in the sample using a data-driven approach, and 2) determine their correspondence with traditional diagnostic statuses. Six clusters representing different cognitive profiles were identified, including participants with varying forms of cognitive impairment. Diagnostic status did not correspond with cluster-membership, providing evidence for the application of transdiagnostic approaches to understanding cognitive heterogeneity in children and adolescents with neurodevelopmental disorders. Additionally, the findings suggest that many typically developing participants may have undiagnosed learning difficulties, emphasizing the need for accessible cognitive assessment tools in school-based settings.

Every minute matters: Improving outcomes for penetrating trauma through prehospital advanced resuscitative care.

INTRODUCTION: Prehospital resuscitation with blood products is gaining popularity for patients with traumatic hemorrhage. The MEDEVAC trial demonstrated a survival benefit exclusively among patients who received blood or plasma within 15 minutes of air medical evacuation. In fast-paced urban EMS systems with a high incidence of penetrating trauma, mortality data based on the timing to first blood administration is scarce. We hypothesize a survival benefit in patients with severe hemorrhage when blood is administered within the first 15 minutes of EMS patient contact. METHODS: This was a retrospective analysis of a prospective database of prehospital blood (PHB) administration between 2021 and 2023 in an urban EMS system facing increasing rates of gun violence. PHB patients were compared to trauma registry controls from an era before prehospital blood utilization (2016-2019). Included were patients with penetrating injury and SBP ≤ 90 mmHg at initial EMS evaluation that received at least one unit of blood product after injury. Excluded were isolated head trauma or prehospital cardiac arrest. Time to initiation of blood administration before and after PHB implementation and in-hospital mortality were the primary variables of interest. RESULTS: A total of 143 patients (PHB = 61, controls = 82) were included for analysis. Median age was 34 years with no difference in demographics. Median scene and transport intervals were longer in the PHB cohort, with a 5-minute increase in total prehospital time. Time to administration of first unit of blood was significantly lower in the PHB vs. control group (8 min vs 27 min; p < 0.01). In-hospital mortality was lower in the PHB vs. control group (7% vs 29%; p < 0.01). When controlling for patient age, NISS, tachycardia on EMS evaluation, and total prehospital time interval, multivariate regression revealed an independent increase in mortality by 11% with each minute delay to blood administration following injury (OR 1.11, 95%CI 1.04-1.19). CONCLUSION: Compared to patients with penetrating trauma and hypotension who first received blood after hospital arrival, resuscitation with blood products was started 19 minutes earlier after initiation of a PHB program despite a 5-minute increase in prehospital time. A survival for early PHB use was demonstrated, with an 11% mortality increase for each minute delay to blood administration. Interventions such as PHB may improve patient outcomes by helping capture opportunities to improve trauma resuscitation closer to the point of injury. LEVEL OF EVIDENCE: Prospective, Level IV.

A design for life: Predicting cognitive performance from lifestyle choices.

Maintaining cognitive capacity through adulthood has been the target of many recent studies that have examined the influence of lifestyle choices such as exercise, diet, and sleeping habits. Many of these studies have focused on a single factor (e.g., diet) and its effect on cognitive abilities; however, humans make numerous lifestyle choices every single day, many of which interact and influence each other. Here, we investigated whether combinations of lifestyle choices can predict better or worse cognitive performance in the general population, and whether optimal combinations of choices existed depending on the cognitive domain. Specifically, we examined 20 self-reported lifestyle choices, such as playing video games, drinking alcohol, and amount of exercise taken, in a sample of almost 10,000 participants. All participants also completed 12 cognitive tests that have been shown to generate three composite cognitive domain scores pertaining to short-term memory, verbal abilities, and reasoning. Using recursive feature elimination and random forest regression, we were able to explain 9% of the variance in short-term memory scores, 8% of the variance in reasoning scores, and 7% of the variance in verbal ability scores. While the regression model provided predictive power in all three domains, these levels indicate that even when considering a large number of lifestyle choices, there remains a considerable degree of variability in predicting short-term memory, reasoning and verbal abilities. Thus, while some modifiable lifestyle factors may have an impact on cognitive capacity, there likely exists no single optimal design for life.

T2* Mapping of Placental Oxygenation to Estimate Fetal Cortical and Subcortical Maturation.

This cohort study investigates the association between T2* mapping of placental oxygenation and cortical and subcortical fetal brain volumes in typically developing fetuses scanned longitudinally in the third trimester.

Identifying cognitive profiles in children with neurodevelopmental disorders using online cognitive testing.

Children with neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD) tend to exhibit similar deficits in attention and memory ability. Early screening of cognitive deficits in children with NDDs, particularly in preschool children, is fundamental to improving cognitive and academic outcomes. In order to determine cognitive profiles in children with ASD and ADHD, we developed accessible audiovisual instructions for an online battery of 13 cognitive tests. Children ages 4-16 who were diagnosed with ADHD (n = 83), or ASD (n = 37), or who were typically developing children (TD) (n = 86) were recruited. Data were analyzed using a stepwise Discriminant Analysis to determine which cognitive tasks were the strongest discriminators between the diagnostic groups. Results revealed four tasks reflective of working memory, reasoning, and attentional processes, which correctly classified approximately 53-60% of each group. The ADHD group had lower scores on attentional tasks compared to TD, while ASD group had lower scores on reasoning tasks compared to the TD children, and made more attempts across all four tasks. The results from this study stress the need for cognitive screening assessments that include domain-specific items to improve the characterization of executive function deficits and promote academic achievement in all children with NDDs.

Commonly diagnosed Neurodevelopmental disorders (NDDs) include autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD). Children with NDDs often experience a wide range of cognitive difficulties which can seriously impact their academic, emotional and behavioural outcomes at school. In this study, we used online cognitive tests that were developed for adults. These 'gamified' tasks assess a number of cognitive abilities including working memory, attention, verbal skills, and reasoning. We developed audiovisual instructions to make these tasks more suitable to children with and without NDDs. These tasks were then used in an online sample of children with ASD, ADHD, and typically developing children. We wanted to see how each group of children performed on the tasks, to assess their relative cognitive strengths and difficulties. We found that the tasks could successfully categorize each group of children based on their task performance. The ADHD group had lower scores on attentional tasks compared to TD children. The ASD group had lower scores on reasoning compared to TD children. The cognitive task battery may eventually be used to help identify cognitive difficulties and improve outcomes in children with NDDs.

Faster refill in an urban emergency medical services system saves lives: A prospective preliminary evaluation of a prehospital advanced resuscitative care bundle.

INTRODUCTION: Military experience has demonstrated mortality improvement when advanced resuscitative care (ARC) is provided for trauma patients with severe hemorrhage. The benefits of ARC for trauma in civilian emergency medical services (EMS) systems with short transport intervals are still unknown. We hypothesized that ARC implementation in an urban EMS system would reduce in-hospital mortality. METHODS: This was a prospective analysis of ARC bundle administration between 2021 and 2023 in an urban EMS system with 70,000 annual responses. The ARC bundle consisted of calcium, tranexamic acid, and packed red blood cells via a rapid infuser. Advanced resuscitative care patients were compared with trauma registry controls from 2016 to 2019. Included were patients with a penetrating injury and systolic blood pressure ≤90 mm Hg. Excluded were isolated head trauma or prehospital cardiac arrest. In-hospital mortality was the primary outcome of interest. RESULTS: A total of 210 patients (ARC, 61; controls, 149) met the criteria. The median age was 32 years, with no difference in demographics, initial systolic blood pressure or heart rate recorded by EMS, or New Injury Severity Score between groups. At hospital arrival, ARC patients had lower median heart rate and shock index than controls ( p ≤ 0.03). Fewer patients in the ARC group required prehospital advanced airway placement ( p < 0.001). Twenty-four-hour and total in-hospital mortality were lower in the ARC group ( p ≤ 0.04). Multivariable regression revealed an independent reduction in in-hospital mortality with ARC (odds ratio, 0.19; 95% confidence interval, 0.05-0.68; p = 0.01). CONCLUSION: Early ARC in a fast-paced urban EMS system is achievable and may improve physiologic derangements while decreasing patient mortality. Advanced resuscitative care closer to the point of injury warrants consideration. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Sex- and age-based differences in fetal and early childhood hippocampus maturation: a cross-sectional and longitudinal analysis.

The hippocampus, essential for cognitive and affective processes, develops exponentially with differential trajectories seen in girls and boys, yet less is known about its development during early fetal life until early childhood. In a cross-sectional and longitudinal study, we examined the sex-, age-, and laterality-related developmental trajectories of hippocampal volumes in fetuses, infants, and toddlers associated with age. Third trimester fetuses (27-38 weeks' gestational age), newborns (0-4 weeks' postnatal age), infants (5-50 weeks' postnatal age), and toddlers (2-3 years postnatal age) were scanned with magnetic resonance imaging. A total of 133 datasets (62 female, postmenstrual age [weeks] M = 69.38, SD = 51.39, range = 27.6-195.3) were processed using semiautomatic segmentation methods. Hippocampal volumes increased exponentially during the third trimester and the first year of life, beginning to slow at approximately 2 years. Overall, boys had larger hippocampal volumes than girls. Lateralization differences were evident, with left hippocampal growth beginning to plateau sooner than the right. This period of rapid growth from the third trimester, continuing through the first year of life, may support the development of cognitive and affective function during this period.

Subcortical brain volumes in neonatal hypoxic-ischemic encephalopathy.

BACKGROUND: Despite treatment with therapeutic hypothermia, hypoxic-ischemic encephalopathy (HIE) is associated with adverse developmental outcomes, suggesting the involvement of subcortical structures including the thalamus and basal ganglia, which may be vulnerable to perinatal asphyxia, particularly during the acute period. The aims were: (1) to examine subcortical macrostructure in neonates with HIE compared to age- and sex-matched healthy neonates within the first week of life; (2) to determine whether subcortical brain volumes are associated with HIE severity. METHODS: Neonates (n = 56; HIE: n = 28; Healthy newborns from the Developing Human Connectome Project: n = 28) were scanned with MRI within the first week of life. Subcortical volumes were automatically extracted from T1-weighted images. General linear models assessed between-group differences in subcortical volumes, adjusting for sex, gestational age, postmenstrual age, and total cerebral volumes. Within-group analyses evaluated the association between subcortical volumes and HIE severity. RESULTS: Neonates with HIE had smaller bilateral thalamic, basal ganglia and right hippocampal and cerebellar volumes compared to controls (all, p < 0.02). Within the HIE group, mild HIE severity was associated with smaller volumes of the left and right basal ganglia (both, p < 0.007) and the left hippocampus and thalamus (both, p < 0.04). CONCLUSIONS: Findings suggest that, despite advances in neonatal care, HIE is associated with significant alterations in subcortical brain macrostructure. IMPACT: Compared to their healthy counterparts, infants with HIE demonstrate significant alterations in subcortical brain macrostructure on MRI acquired as early as 4 days after birth. Smaller subcortical volumes impacting sensory and motor regions, including the thalamus, basal ganglia, and cerebellum, were seen in infants with HIE. Mild and moderate HIE were associated with smaller subcortical volumes.

Hippocampus long-axis specialization throughout development: A meta-analysis.

The human adult hippocampus can be subdivided into the head, or anterior hippocampus and its body and tail, or posterior hippocampus, and a wealth of functional differences along the longitudinal axis have been reported. One line of literature emphasizes specialization for different aspects of cognition, whereas another emphasizes the unique role of the anterior hippocampus in emotional processing. While some research suggests that functional differences in memory between the anterior and posterior hippocampus appear early in development, it remains unclear whether this is also the case for functional differences in emotion processing. The goal of this meta-analysis was to determine whether the long-axis functional specialization observed in adults is present earlier in development. Using a quantitative meta-analysis, long-axis functional specialization was assessed using the data from 26 functional magnetic resonance imaging studies, which included 39 contrasts and 804 participants ranging in age from 4 to 21 years. Results indicated that emotion was more strongly localized to the anterior hippocampus, with memory being more strongly localized to the posterior hippocampus, demonstrating long-axis specialization with regard to memory and emotion in children similar to that seen in adults. An additional analysis of laterality indicated that while memory was left dominant, emotion was processed bilaterally.

Default mode network functional connectivity strength in utero and the association with fetal subcortical development.

The default mode network is essential for higher-order cognitive processes and is composed of an extensive network of functional and structural connections. Early in fetal life, the default mode network shows strong connectivity with other functional networks; however, the association with structural development is not well understood. In this study, resting-state functional magnetic resonance imaging and anatomical images were acquired in 30 pregnant women with singleton pregnancies. Participants completed 1 or 2 MR imaging sessions, on average 3 weeks apart (43 data sets), between 28- and 39-weeks postconceptional ages. Subcortical volumes were automatically segmented. Activation time courses from resting-state functional magnetic resonance imaging were extracted from the default mode network, medial temporal lobe network, and thalamocortical network. Generalized estimating equations were used to examine the association between functional connectivity strength between default mode network-medial temporal lobe, default mode network-thalamocortical network, and subcortical volumes, respectively. Increased functional connectivity strength in the default mode network-medial temporal lobe network was associated with smaller right hippocampal, left thalamic, and right caudate nucleus volumes, but larger volumes of the left caudate. Increased functional connectivity strength in the default mode network-thalamocortical network was associated with smaller left thalamic volumes. The strong associations seen among the default mode network functional connectivity networks and regionally specific subcortical volume development indicate the emergence of short-range connectivity in the third trimester.

A radiofrequency coil for infants and toddlers.

Infants and toddlers are a challenging population upon which to perform magnetic resonance imaging (MRI) of the brain, both in research and clinical settings. Because of the large range in head size during the early years of development, paediatric neuro-MRI requires a radiofrequency (RF) coil, or set of coils, that is tailored to head size to provide the highest image quality. Mitigating techniques must also be employed to reduce and correct for subject motion. This manuscript describes an RF coil with a tailored mechanical-electrical design that can adapt to the head size of 3-month-old infants to 3-year-old toddlers. The RF coil was designed with tight-fitting coil elements to improve the signal-to-noise ratio (SNR) in comparison with commercially available adult head coils, while simultaneously aiding in immobilization. The coil was designed without visual obstruction to facilitate an unimpeded view of the child's face and the potential application of camera or motion-tracking systems. Despite the lack of elements over the face, the paediatric coil produced higher SNR over most of the brain compared with adult coils, including more than twofold in the periphery. Acceleration rates of fourfold in each Cartesian direction could be achieved. High SNR allowed for short acquisition times through accelerated imaging protocols and reduced the probability of motion during a scan. Modification of the acquisition protocol, with immobilization of the head through the adjustable coil geometry, and subsequently being combined with a motion-tracking system, provides a compelling platform for scanning paediatric populations without sedation and with improved image quality.

Funcmasker-flex: An Automated BIDS-App for Brain Segmentation of Human Fetal Functional MRI data.

Fetal functional magnetic resonance imaging (fMRI) offers critical insight into the developing brain and could aid in predicting developmental outcomes. As the fetal brain is surrounded by heterogeneous tissue, it is not possible to use adult- or child-based segmentation toolboxes. Manually-segmented masks can be used to extract the fetal brain; however, this comes at significant time costs. Here, we present a new BIDS App for masking fetal fMRI, funcmasker-flex, that overcomes these issues with a robust 3D convolutional neural network (U-net) architecture implemented in an extensible and transparent Snakemake workflow. Open-access fetal fMRI data with manual brain masks from 159 fetuses (1103 total volumes) were used for training and testing the U-net model. We also tested generalizability of the model using 82 locally acquired functional scans from 19 fetuses, which included over 2300 manually segmented volumes. Dice metrics were used to compare performance of funcmasker-flex to the ground truth manually segmented volumes, and segmentations were consistently robust (all Dice metrics ≥ 0.74). The tool is freely available and can be applied to any BIDS dataset containing fetal bold sequences. Funcmasker-flex reduces the need for manual segmentation, even when applied to novel fetal functional datasets, resulting in significant time-cost savings for performing fetal fMRI analysis.

Postnatal maternal distress, infant subcortical brain macrostructure and emotional regulation.

BACKGROUND: Maternal distress is associated with an increased risk for adverse emotional development in infants, including difficulties with emotion regulation. Prenatal maternal distress has been associated with alterations in infant brain development. However, less is known about these associations with postnatal maternal distress, despite this being an important modifiable risk factor that can promote healthy brain development and emotional outcomes in infants. METHODS & RESULTS: Infants underwent magnetic resonance imaging (MRI) and mothers completed standardized questionnaires concerning their levels of perceived distress 2-5 months postpartum. Infant emotion regulation was assessed at 8-11 months via maternal report. When examining the associations between maternal distress and infant macrostructure, maternal anxiety was associated with infant right pallidum volumes. Increased display of negative emotions at 8-11 months of age was associated with smaller hippocampal volumes and this association was stronger in girls than boys. CONCLUSION: Findings suggest that postnatal maternal distress may be associated with early infant brain development and emphasize the importance of maternal mental health, supporting previous work. Furthermore, macrostructural properties of infant subcortical structures may be further investigated as potential biomarkers to identify infants at risk of adverse emotional outcomes.

Semi-automatic segmentation of the fetal brain from magnetic resonance imaging.

Background: Volumetric measurements of fetal brain maturation in the third trimester of pregnancy are key predictors of developmental outcomes. Improved understanding of fetal brain development trajectories may aid in identifying and clinically managing at-risk fetuses. Currently, fetal brain structures in magnetic resonance images (MRI) are often manually segmented, which requires both time and expertise. To facilitate the targeting and measurement of brain structures in the fetus, we compared the results of five segmentation methods applied to fetal brain MRI data to gold-standard manual tracings. Methods: Adult women with singleton pregnancies (n = 21), of whom five were scanned twice, approximately 3 weeks apart, were recruited [26 total datasets, median gestational age (GA) = 34.8, IQR = 30.9-36.6]. T2-weighted single-shot fast spin echo images of the fetal brain were acquired on 1.5T and 3T MRI scanners. Images were first combined into a single 3D anatomical volume. Next, a trained tracer manually segmented the thalamus, cerebellum, and total cerebral volumes. The manual segmentations were compared with five automatic methods of segmentation available within Advanced Normalization Tools (ANTs) and FMRIB's Linear Image Registration Tool (FLIRT) toolboxes. The manual and automatic labels were compared using Dice similarity coefficients (DSCs). The DSC values were compared using Friedman's test for repeated measures. Results: Comparing cerebellum and thalamus masks against the manually segmented masks, the median DSC values for ANTs and FLIRT were 0.72 [interquartile range (IQR) = 0.6-0.8] and 0.54 (IQR = 0.4-0.6), respectively. A Friedman's test indicated that the ANTs registration methods, primarily nonlinear methods, performed better than FLIRT (p < 0.001). Conclusion: Deformable registration methods provided the most accurate results relative to manual segmentation. Overall, this semi-automatic subcortical segmentation method provides reliable performance to segment subcortical volumes in fetal MR images. This method reduces the costs of manual segmentation, facilitating the measurement of typical and atypical fetal brain development.

Redesigning a Clinical Advancement Program to Promote and Strengthen Competencies of Clinical Nurses.

Clinical advancement programs (CAPs) benefit direct care nursing staff, patients, and healthcare institutions. As standards in nursing practice and workforce evolve, changes in CAPs are necessary. In this quality improvement project, nursing leadership and a 15-member nurse committee redesigned a CAP using Benner's Novice to Expert Model. Changes included self-selection of specialty tracks by shadowing senior nurses in direct patient care, education, and leadership. CAPs increase satisfaction, collaboration, and generation of innovative knowledge.

Machine learning-based predictive modeling of resilience to stressors in pregnant women during COVID-19: A prospective cohort study.

During the COVID-19 pandemic, pregnant women have been at high risk for psychological distress. Lifestyle factors may be modifiable elements to help reduce and promote resilience to prenatal stress. We used Machine-Learning (ML) algorithms applied to questionnaire data obtained from an international cohort of 804 pregnant women to determine whether physical activity and diet were resilience factors against prenatal stress, and whether stress levels were in turn predictive of sleep classes. A support vector machine accurately classified perceived stress levels in pregnant women based on physical activity behaviours and dietary behaviours. In turn, we classified hours of sleep based on perceived stress levels. This research adds to a developing consensus concerning physical activity and diet, and the association with prenatal stress and sleep in pregnant women. Predictive modeling using ML approaches may be used as a screening tool and to promote positive health behaviours for pregnant women.

Prenatal and postpartum maternal mental health and neonatal motor outcomes during the COVID-19 pandemic.

Background: Rates of prenatal and postpartum stress and depression in pregnant individuals have increased during the COVID-19 pandemic. Perinatal maternal mental health has been linked to worse motor development in offspring, with motor deficits appearing in infancy and early childhood. We aimed to evaluate the relationship between prenatal and postpartum stress and depression and motor outcome in infants born during the COVID-19 pandemic. Methods: One hundred and seventeen participants completed an online prospective survey study at two timepoints: during pregnancy and within 2 months postpartum. Depression was self-reported using the Edinburgh Perinatal/Postpartum Depression Scale (EPDS), and stress via the Perceived Stress Scale (PSS). Mothers reported total infant motor ability (fine and gross) using the interRAI 0-3 Developmental Domains questionnaire. Results: Prenatal (EPDS median=10.0, interquartile range[IQR]=6.0 - 14.0, B=-0.035, 95%CI=-0.062 to -0.007, p = 0.014) and postpartum maternal depression outcomes (median=7, IQR=4-12, B=-0.037, 95%CI= -0.066 to -0.008, p = 0.012) were significantlynegatively associated with total infant motor ability. Neither pregnancy nor postpartum perceived stress was associated with infant motor function. A cluster analysis revealed that preterm and low-birth weight infants whose mothers reported elevated depressive symptoms during pregnancy and in the postpartum period had the poorest motor outcomes. Conclusions: Prenatal and postpartum depression, but not stress, was associated with early infant motor abilities. Preterm and low-birth weight infants whose mothers reported elevated depressive symptoms maybe at-risk of experiencing poor motor outcomes. These results highlight the importance of identifying pre- and postnatal maternal mental health issues, especially during the ongoing COVID-19 pandemic.

Depression in pregnant women with and without COVID-19.

Evidence suggests that pregnant women who test positive for COVID-19 may develop more severe illness than non-pregnant women and may be at greater risk for psychological distress. The relationship between COVID-19 status (positive, negative, never tested) and symptoms of depression was examined in a survey study (May to September 2020) of pregnant women (n = 869). Pregnant women who reported testing positive for COVID-19 were significantly more likely to report depressive symptoms compared with women who tested negative (P = 0.027) and women who were never tested (P = 0.005). Findings indicate that pregnant women who test positive for COVID-19 should be screened and monitored for depressive symptoms.

Individual differences in representational similarity of first and second languages in the bilingual brain.

Current theories of bilingualism disagree on the extent to which separate brain regions are used to maintain or process one's first and second language. The present study took a novel multivariate approach to address this question. We examined whether bilinguals maintain distinct neural representations of two languages; specifically, we tested whether brain areas that are involved in processing word meaning in either language are reliably representing each language differently, and whether language representation is influenced by individual differences in proficiency level and age of acquisition (AoA) of L2. Thirty-one English-Mandarin bilingual adults performed a picture-word matching task in both languages. We then used representational similarity analysis to examine which brain regions reliably showed different patterns of activity for each language. We found that both proficiency and AoA predicted dissimilarity between language representations in several brain areas within the language network as well as several regions of the ventral visual pathway, demonstrating that top-down language knowledge and individual language experience shapes concept representation in this processing stream. The results support the model of an integrated language system in bilinguals, along with a novel description of how representations for each language change with proficiency level and L2 AoA.