Developmental trajectories of EEG aperiodic and periodic components in children 2-44 months of age.

The development of neural circuits has long-lasting effects on brain function, yet our understanding of early circuit development in humans remains limited. Here, periodic EEG power features and aperiodic components were examined from longitudinal EEGs collected from 592 healthy 2-44 month-old infants, revealing age-dependent nonlinear changes suggestive of distinct milestones in early brain maturation. Developmental changes in periodic peaks include (1) the presence and then absence of a 9-10 Hz alpha peak between 2-6 months, (2) nonlinear changes in high beta peaks (20-30 Hz) between 4-18 months, and (3) the emergence of a low beta peak (12-20 Hz) in some infants after six months of age. We hypothesized that the emergence of the low beta peak may reflect maturation of thalamocortical network development. Infant anesthesia studies observe that GABA-modulating anesthetics do not induce thalamocortical mediated frontal alpha coherence until 10-12 months of age. Using a small cohort of infants (n = 23) with EEG before and during GABA-modulating anesthesia, we provide preliminary evidence that infants with a low beta peak have higher anesthesia-induced alpha coherence compared to those without a low beta peak.

Caregiving stress and maternal mental health during the COVID-19 pandemic.

It has now been extensively documented that parental mental health has deteriorated since the beginning of the COVID-19 pandemic. Although pandemic-related stress has been widespread, parents faced the unique challenge of navigating remote schooling. Parental oversight of children's education, loss of access to school supportive resources, and the challenges of remote learning may have been most problematic for parents of children with or at elevated risk for mental health difficulties. In the current study, we examined interactive effects of parent-reported pandemic-related caregiving stress and child internalizing and externalizing problems on parental depressive symptoms in a community-based cohort (N = 115) in the Northeast of the United States. Results indicated that parents experiencing higher levels of pandemic-related caregiving stress whose children exhibited elevated externalizing behaviors reported heightened levels of depressive symptoms. Greater child internalizing problems were associated with higher parental depressive symptoms independent of caregiving stress. These findings point to conditions that might heighten risk for parent mental health challenges in the context of ongoing remote or hybrid learning and pandemic-associated restrictions. Further, the findings point to conditions and characteristics that may be screened to identify and intervene with vulnerable families to mitigate mental health problems.

Resting state EEG in young children with Tuberous Sclerosis Complex.

Background: Tuberous Sclerosis Complex (TSC) manifests behaviorally with features of autism, epilepsy, and intellectual disability. Resting state electroencephalography (EEG) offers a window into neural oscillatory activity and may serve as an intermediate biomarker between gene expression and behavioral manifestations. Such a biomarker could be useful in clinical trials as an endpoint or predictor of treatment response. However, seizures and antiepileptic medications also affect resting neural oscillatory activity and could undermine the utility of resting state EEG features as biomarkers in neurodevelopmental disorders such as TSC. Methods: This paper compares resting state EEG features in a cross-sectional cohort of young children with TSC (n=49, ages 12-37 months) to 49 age- and sex-matched typically developing controls. Within children with TSC, associations were examined between resting state EEG features, seizure severity composite score, and use of GABA agonists. Results: Compared to matched typically developing controls, children with TSC showed significantly greater alpha and beta power in permutation cluster analyses iterated across a broad frequency range (2-50Hz). Children with TSC also showed significantly greater aperiodic offset after power spectra were parameterized using SpecParam into aperiodic and periodic components. Within children with TSC, greater seizure severity was significantly related to increased periodic peak beta power. Use of GABA agonists was also independently and significantly associated with increased periodic peak beta power; the interaction between seizure severity and GABA agonist use had no significant effect on peak beta power. Conclusions: The elevated peak beta power observed in children with TSC compared to matched typically developing controls may be driven by both seizures and GABA agonist use. It is recommended to collect seizure and mediation data alongside EEG data for clinical trials. These results highlight the challenge of using resting state EEG features as biomarkers in trials with neurodevelopmental disabilities when epilepsy and anti-epileptic medication are common.

Neural network classification of beams carrying orbital angular momentum after propagating through controlled experimentally generated optical turbulence.

We generate an alphabet of spatially multiplexed Laguerre-Gaussian beams carrying orbital angular momentum, which are demultiplexed at reception by a convolutional neural network (CNN). In this investigation, a methodology for optimizing alphabet design for best classification rates is proposed, and three 256-symbol alphabets are designed for performance evaluation in optical turbulence. The beams were propagated in three environments: through underwater optical turbulence generated by Rayleigh-Bénard (RB) convection (C n2≅10-11 m -2/3), through a simulated propagation path derived from the Nikishov spectrum (C n2≅10-13 m -2/3), and through optical turbulence from a thermal point source located in a water tank (C n2≅10-10 m -2/3). We report a classification accuracy of 93.1% for the RB environment, 99.99% in simulation, and 48.5% in the point source environment. The project demonstrates that the CNN can classify the complex alphabet symbols in a practical turbulent flow that exhibits strong optical turbulence, provided sufficient training data is available and testing data is representative of the specific environment. We find the most important factor in a high classification accuracy is a diversification in the intensity profiles of the alphabet symbols.

Long-term measurement and characterization of boundary layer optical turbulence.

The United States Naval Academy long-term scintillation measurement campaign was a multi-year effort to characterize optical turbulence in the near-maritime atmospheric boundary layer (ABL). At its core, the field experiment consists of in situ measurements of bulk atmospheric and oceanographic parameters, as well as path-averaged measurements of the refractive index structure parameter, C n2, collected using a large-aperture scintillometer. The field experiment ran from January 1st, 2020, through September 26th, 2023, representing the most comprehensive collection of optical turbulence measurements in the near-maritime ABL to date. Long-term measurements enable researchers to evaluate existing theory and develop new models applicable to this environment. The present study characterizes some of the physical relationships that affect optical turbulence. This characterization focuses on the relationship between local optical turbulence and select atmospheric and oceanographic parameters. The impact of temperature gradients on the extent of optical turbulence was analyzed, along with its interactions with relative humidity and wind speed. The diurnal and seasonal variations in measured C n2 were examined, with comparisons drawn against other environments. Further information and the full dataset are publicly available through the optical turbulence benchmark repository [Jellen et al., GitHub, 2023].

Prediction of chronological age from resting-state EEG power in the first three years of life.

The infant brain undergoes rapid and significant developmental changes in the first three years of life. Understanding these changes through the prediction of chronological age using neuroimaging data can provide insights into typical and atypical brain development. We utilized longitudinal resting-state EEG data from 457 typically developing infants, comprising 938 recordings, to develop age prediction models. The multilayer perceptron model demonstrated the highest accuracy with an R2 of 0.82 and a mean absolute error of 92.4 days. Aperiodic offset and periodic theta, alpha, and beta power were identified as key predictors of age via Shapley values. Application of the model to EEG data from infants later diagnosed with autism spectrum disorder or Down syndrome revealed significant underestimations of chronological age. This study establishes the feasibility of using EEG to assess brain maturation in early childhood and supports its potential as a clinical tool for early identification of alterations in brain development.

Electroencephalographic Correlates of Clinical Severity in the Natural history study of RTT and Related Disorders.

OBJECTIVE: This study was undertaken to characterize quantitative electroencephalographic (EEG) features in participants from the Natural history study of RTT and Related Disorders and to assess the potential for these features to act as objective measures of cortical function for Rett syndrome (RTT). METHODS: EEG amplitude and power features were derived from the resting EEG of 60 females with RTT (median age = 10.7 years) and 26 neurotypical females (median age = 10.6 years). Analyses focus on group differences and within the RTT group, associations between the EEG parameters and clinical severity. For a subset of participants (n = 20), follow-up data were available for assessing the reproducibility of the results and the stability in the parameters over 1 year. RESULTS: Compared to neurotypical participants, participants with RTT had greater amplitude variability and greater low-frequency activity as reflected by greater delta power, more negative 1/f slope, and lower theta/delta, alpha/delta, beta/delta, alpha/theta, and beta/theta ratios. Greater delta power, more negative 1/f slope, and lower power ratios were associated with greater severity. Analyses of year 1 data replicated the associations between 1/f slope and power ratios and clinical severity and demonstrated good within-subject consistency in these measures. INTERPRETATION: Overall, group comparisons reflected a greater predominance of lower versus higher frequency activity in participants with RTT, which is consistent with prior clinical interpretations of resting EEG in this population. The observed associations between the EEG power measures and clinical assessments and the repeatability of these measures underscore the potential for EEG to provide an objective measure of cortical function and clinical severity for RTT. ANN NEUROL 2024;96:175-186.

Mapping the cellular biogeography of human bone marrow niches using single-cell transcriptomics and proteomic imaging.

Non-hematopoietic cells are essential contributors to hematopoiesis. However, heterogeneity and spatial organization of these cells in human bone marrow remain largely uncharacterized. We used single-cell RNA sequencing (scRNA-seq) to profile 29,325 non-hematopoietic cells and discovered nine transcriptionally distinct subtypes. We simultaneously profiled 53,417 hematopoietic cells and predicted their interactions with non-hematopoietic subsets. We employed co-detection by indexing (CODEX) to spatially profile over 1.2 million cells. We integrated scRNA-seq and CODEX data to link predicted cellular signaling with spatial proximity. Our analysis revealed a hyperoxygenated arterio-endosteal neighborhood for early myelopoiesis, and an adipocytic localization for early hematopoietic stem and progenitor cells (HSPCs). We used our CODEX atlas to annotate new images and uncovered mesenchymal stromal cell (MSC) expansion and spatial neighborhoods co-enriched for leukemic blasts and MSCs in acute myeloid leukemia (AML) patient samples. This spatially resolved, multiomic atlas of human bone marrow provides a reference for investigation of cellular interactions that drive hematopoiesis.

Neurodevelopment of children exposed to prolonged anesthesia in infancy: GABA study interim analysis of resting-state brain networks at 2, 4, and 10-months old.

BACKGROUND: Previous studies have raised concerns regarding neurodevelopmental impacts of early exposures to general anesthesia and surgery. Electroencephalography (EEG) can be used to study ontogeny of brain networks during infancy. As a substudy of an ongoing study, we examined measures of functional connectivity in awake infants with prior early and prolonged anesthetic exposures and in control infants. METHODS: EEG functional connectivity was assessed using debiased weighted phase lag index at source and sensor levels and graph theoretical measures for resting state activity in awake infants in the early anesthesia (n = 26 at 10 month visit, median duration of anesthesia = 4 [2, 7 h]) and control (n = 38 at 10 month visit) groups at ages approximately 2, 4 and 10 months. Theta and low alpha frequency bands were of primary interest. Linear mixed models incorporated impact of age and cumulative hours of general anesthesia exposure. RESULTS: Models showed no significant impact of cumulative hours of general anesthesia exposure on debiased weighted phase lag index, characteristic path length, clustering coefficient or small-worldness (conditional R2 0.05-0.34). An effect of age was apparent in many of these measures. CONCLUSIONS: We could not demonstrate significant impact of general anesthesia in the first months of life on early development of resting state brain networks over the first postnatal year. Future studies will explore these networks as these infants grow older.

Perinatal inflammation, fetal growth restriction, and long-term neurodevelopmental impairment in Bangladesh.

BACKGROUND: There are limited data on the impact of perinatal inflammation on child neurodevelopment in low-middle income countries and among growth-restricted infants. METHODS: Population-based, prospective birth cohort study of 288 infants from July 2016-March 2017 in Sylhet, Bangladesh. Umbilical cord blood was analyzed for interleukin(IL)-1α, IL-1ß, IL-6, IL-8, and C-reactive protein(CRP). Child neurodevelopment was assessed at 24 months with Bayley-III Scales of Infant Development. We determined associations between cord blood inflammation and neurodevelopmental outcomes, controlling for potential confounders. RESULTS: 248/288 (86%) live born infants were followed until 24 months, among whom 8.9% were preterm and 45.0% small-for-gestational-age(SGA) at birth. Among all infants, elevated concentrations (>75%) of CRP and IL-6 at birth were associated with increased odds of fine motor delay at 24 months; elevated CRP was also associated with lower receptive communication z-scores. Among SGA infants, elevated IL-1α was associated with cognitive delay, IL-8 with language delay, CRP with lower receptive communication z-scores, and IL-1ß with lower expressive communication and motor z-scores. CONCLUSIONS: In rural Bangladesh, perinatal inflammation was associated with impaired neurodevelopment at 24 months. The associations were strongest among SGA infants and noted across several biomarkers and domains, supporting the neurobiological role of inflammation in adverse fetal development, particularly in the setting of fetal growth restriction. IMPACT: Cord blood inflammation was associated with fine motor and language delays at 24 months of age in a community-based cohort in rural Bangladesh. 23.4 million infants are born small-for-gestational-age (SGA) globally each year. Among SGA infants, the associations between cord blood inflammation and adverse outcomes were strong and consistent across several biomarkers and neurodevelopmental domains (cognitive, motor, language), supporting the neurobiological impact of inflammation prominent in growth-restricted infants. Prenatal interventions to prevent intrauterine growth restriction are needed in low- and middle-income countries and may also result in long-term benefits on child development.

Resting Frontal Gamma Power is Associated with Both Expressive Language and Non-verbal Cognitive Abilities in Young Autistic Children.

Previous research links resting frontal gamma power to key developmental outcomes in young neurotypical (NT) children and infants at risk for language impairment. However, it remains unclear whether gamma power is specifically associated with language or with more general cognitive abilities among young children diagnosed with autism spectrum disorder (ASD). The current study evaluates differences in resting frontal gamma power between young autistic and NT children and tests whether gamma power is uniquely associated with individual differences in expressive language, receptive language and non-verbal cognitive abilities in autistic and NT children. Participants included 48 autistic children and 58 age- and sex-matched NT children (ages 22-60 months). Baseline electroencephalography (EEG) recordings were acquired from each participant. Children also completed the Mullen Scales of Early Learning (MSEL). We found that frontal gamma power at rest did not differ between autistic and NT children. Among autistic children, reduced frontal gamma power was significantly associated with both higher expressive language skills and higher non-verbal cognitive skills, controlling for age and sex. The interaction between frontal gamma power and diagnostic status no longer explained unique variance in expressive language skills after controlling for variance associated with non-verbal cognitive skills across autistic and NT children. Together, these findings suggest that reduced gamma power is associated with both better expressive language and non-verbal cognitive skills among young autistic children. Moreover, associations between high frequency neural activity and cognition are not specific to verbal abilities but reflect neural mechanisms associated with general higher-order cognitive abilities in ASD.

Foster Care Leads to Lower Irritability Among Adolescents with a History of Early Psychosocial Deprivation.

Irritability reflects a propensity for frustration and anger, and is a transdiagnostic symptom of both externalizing and internalizing psychopathology. While early adverse experiences are associated with higher levels of irritability, experiences of early psychosocial deprivation and whether family-based placements can mitigate the impact on subsequent irritability, remain underexplored. The current study examined irritability in 107 16-year-olds with a history of institutional care from a randomized controlled trial of foster care as an alternative to institutional care and 49 community comparison children. At age 16 years, irritability was assessed using parent- and self-report forms of the Affective Reactivity Index. Compared to community adolescents, those with a history of institutional care exhibited significantly elevated irritability levels. Among those who experienced institutional care, those randomized to foster care had lower levels of irritability compared to participants randomized to the care-as-usual group, and this effect persists after controlling for baseline negative emotionality. These findings suggest a causal link between high-quality foster care and lower irritability following psychosocial deprivation. Additionally, longer duration in institutional care and non-family placement at age 16 years were associated with higher levels of irritability, highlighting the role of caregiving in explaining variation in irritability in adolescence. Policies that support long-term, high-quality family placements for children without regular caregivers should be prioritized.

Linking caregiving quality during infancy to brain activity in early childhood and later executive function.

There is no relationship more vital than the one a child shares with their primary caregivers early in development. Yet many children worldwide are raised in settings that lack the warmth, connection, and stimulation provided by a responsive primary caregiver. In this study, we used data from the Bucharest Early Intervention Project (BEIP), a longitudinal study of institutionally-reared and family-reared children, to test how caregiving quality during infancy is associated with average EEG power over the first 3.5 years of life in alpha, beta, and theta frequency bands, and associations with later executive function (EF) at age 8 years. The sample comprised 189 children (129 institutionally-reared; 60 family-reared) who contributed data on observed caregiving quality during infancy (baseline; average age of 22 months), resting EEG power at baseline, 30, and 42 months, and performance-based data on a series of EF tasks at 8 years. Using Bayesian estimation, observed caregiving quality at baseline was marginally linked with higher average alpha and beta power, and lower theta power, from baseline to 42 months. In turn, higher average beta power and lower average theta power were marginally associated with higher EF at 8 years. In indirect effects models, higher caregiving quality at baseline was associated with higher EF at 8 years, with a marginal indirect effect through average theta power from baseline to 42 months. Variation in the quality of the early caregiving environment may be associated with later executive function, which is partially underpinned by individual differences in brain activity during early childhood. RESEARCH HIGHLIGHTS: Examined associations between caregiving quality during infancy, brain activity during early childhood, and executive function during mid-childhood in sample of never-institutionalized and institutionally-reared children. Significant associations between higher quality caregiving during infancy and higher executive function during middle childhood. Marginal associations between caregiving quality during infancy and brain activity during early childhood. Marginal associations between brain activity during early childhood and executive function during mid-childhood.

The infant gut microbiome and cognitive development in malnutrition.

Malnutrition affects 195 million children under the age of five worldwide with long term effects that include impaired cognitive development. Brain development occurs rapidly over the first 36 months of life. Whilst seemingly independent, changes to the brain and gut microbiome are linked by metabolites, hormones, and neurotransmitters as part of the gut-brain axis. In the context of severe malnutrition, the composition of the gut microbiome and the repertoire of biochemicals exchanged via the gut-brain axis vary when compared to healthy individuals. These effects are primarily due to the recognized interacting determinants, macro- and micronutrient deficiencies, infection, infestations and toxins related to poor sanitation, and a dearth of psycho-social stimulation. The standard of care for the treatment of severe acute malnutrition is focused on nutritional repletion and weight restoration through the provision of macro- and micronutrients, the latter usually in excess of recommended dietary allowances (RDA). However, existing formulations and supplements have not been designed to specifically address key recovery requirements for brain and gut microbiome development. Animal model studies indicate that treatments targeting the gut microbiome could improve brain development. Despite this, research on humans targeting the gut microbiome with the aim of restoring brain functionality are scarce. We conclude that there is a need for assessment of cognition and the use of various tools that permit visualization of the brain anatomy and function (e.g., Magnetic resonance imaging (MRI), functional near-infrared spectroscopy (fNIRS), electroencephalogram (EEG)) to understand how interventions targeting the gut microbiome impact brain development.

Acute Total Hip Arthroplasty Following Acetabular Fracture is Associated With a High Risk of Revision, Dislocation, and Periprosthetic Fracture.

BACKGROUND: The aim of this study was to compare outcomes between acute, subacute, and delayed arthroplasty for acetabular fractures occurring within 1 week, from 1 week to 6 months, or more than 6 months before the index total hip arthroplasty (THA), versus THA without a history of acetabular fracture as a control. METHODS: We analyzed the records of patients undergoing primary THA who were enrolled in a national database for at least 2 years before and after the index procedure. Patients who had an initial diagnostic code for acetabular fracture occurring less than 1 week, from 1 week to 6 months, or at least more than 6 months before the THA were classified as acute THA (aTHA), subacute THA (saTHA), or delayed THA (dTHA), respectively. The control group was patients undergoing THA who did not have a history of acetabular fracture. There were 430,349 control primary THAs, 462 aTHAs, 675 saTHAs, and 1,162 dTHAs. RESULTS: After adjusting for age, sex, region, and comorbidities, patients who had an aTHA and saTHA experienced statistically significant increased odds of revision, dislocation, and periprosthetic fracture compared to primary THA without a history of acetabular fracture. Similarly, dTHA was associated with increased odds of revision, dislocation, and periprosthetic fractures compared to primary THA. In the multivariate analysis, aTHA had statistically significant higher rates of dislocation when compared to dTHA. CONCLUSIONS: Patients who had a history of acetabular fractures undergoing aTHA, saTHA, or dTHA have significantly increased rates of revision, periprosthetic fracture, and dislocation compared to primary THA in those who did not have a history of acetabular fractures.

Mapping the Cellular Biogeography of Human Bone Marrow Niches Using Single-Cell Transcriptomics and Proteomic Imaging.

The bone marrow is the organ responsible for blood production. Diverse non-hematopoietic cells contribute essentially to hematopoiesis. However, these cells and their spatial organization remain largely uncharacterized as they have been technically challenging to study in humans. Here, we used fresh femoral head samples and performed single-cell RNA sequencing (scRNA-Seq) to profile 29,325 enriched non-hematopoietic bone marrow cells and discover nine transcriptionally distinct subtypes. We next employed CO-detection by inDEXing (CODEX) multiplexed imaging of 18 individuals, including both healthy and acute myeloid leukemia (AML) samples, to spatially profile over one million single cells with a novel 53-antibody panel. We discovered a relatively hyperoxygenated arterio-endosteal niche for early myelopoiesis, and an adipocytic, but not endosteal or perivascular, niche for early hematopoietic stem and progenitor cells. We used our atlas to predict cell type labels in new bone marrow images and used these predictions to uncover mesenchymal stromal cell (MSC) expansion and leukemic blast/MSC-enriched spatial neighborhoods in AML patient samples. Our work represents the first comprehensive, spatially-resolved multiomic atlas of human bone marrow and will serve as a reference for future investigation of cellular interactions that drive hematopoiesis.

Temperament and sex as moderating factors of the effects of exposure to maternal depression on telomere length in early childhood.

Individual differences in sensitivity to context are posited to emerge early in development and to influence the effects of environmental exposures on a range of developmental outcomes. The goal of the current study was to examine the hypothesis that temperament characteristics and biological sex confer differential vulnerability to the effects of exposure to maternal depression on telomere length in early childhood. Telomere length has emerged as a potentially important biomarker of current and future health, with possible mechanistic involvement in the onset of various disease states. Participants comprised a community sample of children followed from infancy to age 3 years. Relative telomere length was assessed from DNA in saliva samples collected at infancy, 2 years, and 3 years. Maternal depressive symptoms and the child temperament traits of negative affectivity, surgency/extraversion, and regulation/effortful control were assessed via maternal report at each timepoint. Analyses revealed a 3-way interaction among surgency/extraversion, sex, and maternal depressive symptoms, such that higher surgency/extraversion was associated with shorter telomere length specifically among males exposed to elevated maternal depressive symptoms. These findings suggest that temperament and sex influence children's susceptibility to the effects of maternal depression on telomere dynamics in early life.

Parental communicative input as a protective factor in Bangladeshi families living in poverty: A multi-dimensional perspective.

Studies from high-income populations have shown that stimulating, supportive communicative input from parents promote children's cognitive and language development. However, fewer studies have identified specific features of input supporting the healthy development of children growing up in low- or middle-income countries. The current study proposes and tests a multi-dimensional framework for understanding whether and how caregiver communicative input mediates the associations between socio-economic conditions and early development. We also examine how caregiver conceptual scaffolding and autonomy support uniquely and synergistically explain variation in child outcomes. Participants were 71 Bangladeshi families with five-year-olds who were exposed to a range of biological and psychosocial hazards from birth. Caregiver-child interactions during snack sharing and semi-structured play were coded for caregiver conceptual scaffolding, autonomy support, and child engagement. Findings indicate that the two dimensions of input were correlated, suggesting that caregivers who provided richer conceptual scaffolds were simultaneously more supportive of children's autonomy. Notably, conceptual scaffolding and autonomy support each mediated associations between maternal education and child verbal intelligence quotient (IQ) scores. Further, caregivers who supported greater autonomy in their children had children who participated in conversations more actively, and these children in turn had higher performance IQ scores. When considered simultaneously, conceptual scaffolding was associated with verbal IQ over and above autonomy support, whereas autonomy support related to child engagement, controlling for conceptual scaffolding. These findings shed new light on how environmental factors may support early development, contributing to the design of family-centered, culturally authentic interventions. A video abstract of this article can be viewed at https://youtu.be/9v_8sIv7ako RESEARCH HIGHLIGHTS: Studies from high-income countries have identified factors mitigating the impacts of socio-economic risks on development. Such research is scarce in low- and middle-income countries. The present study conceptualized and evaluated caregiver communicative input in Bangladeshi families along two interrelated yet distinct dimensions: conceptual scaffolding and autonomy support. Conceptual scaffolding and autonomy support individually mediated associations between maternal education and child verbal IQ, shedding light on protective factors in families living in poverty. Parents providing richer conceptual scaffolds were simultaneously more supportive of children's autonomy. However, the two dimensions each related to cognition and language through unique pathways.