Faculty Bibliography

INTRODUCTION/BACKGROUND:During the COVID-19 pandemic, birthing parents were identified as a high-risk group with greater vulnerability to the harms associated with SARS-CoV-2. This led to necessary changes in perinatal health policies but also to experiences of maternal isolation and loneliness, both in hospital settings, due to infection mitigation procedures, and once home, due to social distancing. METHODS:In this study, we qualitatively explored birthing and postpartum experiences in New York City during the early days of the pandemic when lockdowns were in effect and policies and practices were rapidly changing. Using thematic analysis, our focus was on experiences of isolation, navigating these experiences, and the potential impacts of isolation and loneliness on maternal health for 55 birthing people. RESULTS:Participants described numerous stressors related to isolation during the birthing process, including reconciling their hopes for their birth with the realities of the unknown and separation from partners, family, and friends in the hospital. During the postpartum period, loneliness manifested as having limited or no contact with family and friends, which led to feelings of a need for strengthened social support systems. The impact of these negative experiences shaped mental health. Overall, we found that solitary experiences during birthing and postpartum isolation were major sources of stress for participants in this study. DISCUSSION/CONCLUSIONS:To support impacted families and prepare for future crisis events, clinicians and researchers must prioritize the development of strong clinical and social support structures for perinatal people to ensure both maternal and child health.

Toddler visual attention development correlates with subsequent language, cognitive, and social developmental outcomes. This study investigates the association of maternal trauma on toddler looking behaviors in 39 mother-child dyads from the Western Cape Province, South Africa. At 15 months postpartum, maternal trauma was assessed using the Life Events Checklist and toddler multisensory attention skills were measured using the Multisensory Attention Assessment Protocol (MAAP) during eye-tracking. We used two-way mixed ANOVA to analyze the association of maternal trauma and MAAP condition with attention maintenance, intersensory matching, and attention shifting. This study provides support for the MAAP's reliability with a sample of 15-month-old toddlers from a low-income setting. We observed a significant interaction between MAAP condition and maternal trauma group on attention maintenance, but pairwise comparisons did not meet the threshold for statistical significance. In a stratified analysis, toddlers of mothers in the low trauma exposure group demonstrated significant differences in attention maintenance, intersensory matching, and attention shifting by condition. Unexpectedly, toddlers of mothers in the high trauma exposure group did not exhibit significant differences in these attentional skills, potentially indicating attentional adaptations. Further research is needed to explore the relationship between the intergenerational transmission of trauma on infant and toddler multisensory attention skills in low-income settings.

A long-standing theory for Alzheimer's disease (AD) has been that deterioration of synapses and depressed neuronal activity is a major contributing factor. We review the increasing evidence, in humans and in mouse models, that show that there is often neuronal hyperactivity at early stages rather than decreased activity. We discuss studies in mouse models showing that hyperexcitability can occur long before plaque deposition and memory impairment. In mouse models, a generator of the hyperactivity appears to be the dentate gyrus. We present evidence, based on mouse models, that inhibition of muscarinic cholinergic receptors or medial septal cholinergic neurons can prevent hyperactivity. Therefore, we hypothesize the novel idea that cholinergic neurons are overly active early in the disease, not depressed. In particular we suggest the medial septal cholinergic neurons are overly active and contribute to hyperexcitability. We further hypothesize that the high activity of cholinergic neurons at early ages ultimately leads to their decline in function later in the disease. We review the effects of a prenatal diet that increases choline, the precursor to acetylcholine and modulator of many other functions. In mouse models of AD, maternal choline supplementation (MCS) reduces medial septal cholinergic pathology, amyloid accumulation and hyperexcitability, especially in the dentate gyrus, and improves cognition.

Preterm birth poses a major public health challenge, with significant and heterogeneous developmental impacts. Latent profile analysis was applied to the National Institutes of Health Toolbox performance of 1891 healthy prematurely born children from the Adolescent Brain and Cognitive Development study (970 boys, 921 girls; 10.00 ± 0.61 years; 1.3% Asian, 13.7% Black, 17.5% Hispanic, 57.0% White, 10.4% Other). Three distinct neurocognitive profiles emerged: consistently performing above the norm (19.7%), mixed scores (41.0%), and consistently performing below the norm (39.3%). These profiles were associated with lasting cognitive, neural, behavioral, and academic differences. These findings underscore the importance of recognizing diverse developmental trajectories in prematurely born children, advocating for personalized diagnosis and intervention to enhance care strategies and long-term outcomes for this heterogeneous population.

INTRODUCTION/UNASSIGNED:Assessing sustained attention presents methodological challenges, particularly when spanning diverse populations whose baseline sensorimotor functioning may vary significantly. METHODS/UNASSIGNED:This study introduces the Continuous Performance Critical Stability Task (cpCST), a novel paradigm combining high-density sampling of behavior (30 Hz), individualized calibration, and fixed-difficulty assessment to measure attentional control. In a sample of 166 adults (ages 18-76), we evaluated the psychometric properties of the cpCST's instantaneous reaction time (iRT) metric derived through dynamic time warping. RESULTS/UNASSIGNED:The cpCST demonstrated exceptional reliability (bootstrap split-half r = 0.999) and predictive validity for cognitive performance (flanker and Woodcock-Johnson) and cardiorespiratory fitness (VO2submax). The task achieved high temporal efficiency, with just 2 min of data correlating at r = 0.94 with full-task performance, outperforming a standard arrow-based flanker task. The cpCST's individualized calibration effectively isolated attentional control processes from baseline sensorimotor function, eliminating age-related slowing effects typically observed in reaction time tasks. DISCUSSION/UNASSIGNED:This approach offers methodological advantages for lifespan studies, clinical populations, integration with neurophysiological measures, and computational modeling approaches while addressing limitations of existing attention assessment paradigms.

INTRODUCTION/BACKGROUND:Maternal undernutrition and inflammation in utero may significantly impact the neurodevelopmental potential of offspring. However, few studies have investigated the effects of pregnancy interventions on long-term child growth and development. This study will examine the effects of prenatal nutrition and infection management interventions on long-term growth and neurodevelopmental outcomes of offspring. METHODS:The Enhancing Nutrition and Antenatal Infection Treatment ('ENAT') study (ISRCTN15116516) was a pragmatic, open-label, 2×2 factorial, randomised clinical effectiveness study implemented in 12 rural health centres in Amhara, Ethiopia. The study enrolled 2399 pregnant women who were randomised to receive routine care, an enhanced nutrition package (iron and folic acid, monthly household supply of iodised salt, and micronutrient-fortified balanced energy protein supplement for undernourished women), an enhanced infection management package (genitourinary tract infection screening and treatment, and enhanced deworming), or both packages. In the present Longitudinal Infant Development and Growth study, a subset of 480 children of mothers from ENAT will be recruited equally from each of the four study arms and visited at 12, 18, and 24 months of postnatal age. We will evaluate a range of domains and deploy multiple measures to assess child neurodevelopment, including resting electroencephalography and visual evoked potentials, Hammersmith Infant Neurological Examination, eye-tracking, Bayley Scales of Infant and Toddler Development (Bayley-III), and Magnetic Resonance Imaging (MRI). DISCUSSION/CONCLUSIONS:This study will advance understanding of the impact of nutrition and inflammation in pregnancy on long-term offspring neurodevelopment. This study aims to fill a critical knowledge gap on the benefits of prenatal interventions to promote the health of mothers and their offspring. ETHICS AND DISSEMINATION/BACKGROUND:This study was approved by the Institutional Review Boards of Addis Continental Institute of Public Health (ACIPH/IRB/002/2022) and Mass General Brigham (2023P000461). Results will be disseminated to local and international stakeholders. TRIAL REGISTRATION NUMBER/BACKGROUND:NCT06296238.

PURPOSE/OBJECTIVE:Children and adolescents are experiencing a mental health crisis. Neurodiverse patients have high rates of mental health conditions and worse outcomes. To address this disparity, the Autism Spectrum Disorder Care Pathway was applied to a pediatric emergency department (PED) and Observation Unit (OU) in order to decrease agitation experienced by these patients. METHODS:This prospective cohort study was in a community-based PED and OU from June 2023 to February 2024. A medical education curriculum consisting of a multidisciplinary champion training and toolkit rollout was completed. Agitation was measured by the Behavioral Activity Rating Scale. The primary aim was to decrease frequency of agitation experienced by neurodiverse patients at any point in the PED/OU. The secondary outcome was to decrease pharmacologic intervention and physical restraint use. RESULTS:We captured data from a total of 45 patients, with 19 baseline patients and 26 patients in the intervention group. At baseline, 9 out of 19 (47%) patients experienced agitation at some point in their PED/OU stay. After implementation of the curriculum, agitation levels decreased to 6 out of 26 (23%) patients (p = 0.04). Inter-rater reliability was 0.95. There were 3 incidences of pharmacologic intervention and no physical restraint use. CONCLUSIONS:This pilot medical education curriculum for PED and OU staff members decreased agitation in neurodiverse patients who presented for mental health complaints. This study is the foundation for expansion of the curriculum for use in general emergency departments.

Systematic reviews and meta-analyses have become crucial for evidence-based decision-making in recent decades. However, it is common for the results of multiple reviews on the same topic to be inconsistent, and it is widely recognised that the results of the reviews are not always effectively communicated to healthcare professionals and the lay public. This manuscript proposes a strategy to summarise and communicate the findings of previous systematic reviews and meta-analyses to wider audiences. The proposed approach couples the findings of umbrella reviews with the creation of open-access online platforms that present the results of these umbrella reviews in an accessible way to various stakeholders. The key potential methodological avenues of this approach are presented, and specific examples from the author's own works and those from other teams are provided. An accompanying website (https://u-reach.org/) has been designed to present this Umbrella-Review, Evaluation, Analysis, and Communication Hub (U-REACH) approach and to overcome the technical challenges associated with this type of project (by sharing the code used to build existing U-REACH projects). The present document is intended to serve as a methodological and technical guide for the creation of large-scale projects designed to synthesise and disseminate scientific information to a broad audience.

Numerous recommendations have been made to address the high rates of mental health disorders among justice-involved youth. Few data are available on the use, quality, appropriateness, or availability of services to address these needs. This study examined the relationship between trauma-informed mental health screening, other referral pathways for diagnostic evaluation, subsequent DSM-5 diagnoses, and treatments for evaluated youth. Eligible participants were all youth admitted to New York City secure juvenile detention facilities from September 17, 2015 to October 30, 2016 who remained in the facility for at least five days (N = 786). Of those, 581 (73.9%) were voluntarily screened and 309 (53.2%) later received a diagnostic evaluation. Youth who screened positive for depression, posttraumatic stress disorder, and problematic substance use were more likely to be evaluated. Treatment received was related to diagnosis rather than reason for referral. For youth who were referred for behavioral or emotional concerns, 99.1 percent (114 of 115) of those diagnosed with a neurodevelopmental disorder had attention-deficit/hyperactivity disorder (ADHD). These data are among the first to describe DSM-5 diagnoses and treatment among youth detainees. They highlight the prevalence of ADHD in detained youth and argue for the coordination of universal trauma-informed mental health screening and a structured referral system for this population.

Clinical, neuroimaging and genomics evidence have increasingly underscored a degree of overlap between autism and attention-deficit/hyperactivity disorder (ADHD). This study explores the specific contribution of their core symptoms to shared biology in a sample of N=166 verbal children (6-12 years) with rigorously-established primary diagnoses of either autism or ADHD (without autism). We investigated the associations between inter-individual differences in clinician-based dimensional measures of autism and ADHD symptoms and whole-brain low motion intrinsic functional connectivity (iFC). Additionally, we explored their linked gene expression patterns in silico. Whole-brain multivariate distance matrix regression revealed a transdiagnostic association between autism severity and iFC of two nodes: the middle frontal gyrus of the frontoparietal network and posterior cingulate cortex of the default mode network. Across children, the greater the iFC between these nodes, the more severe the autism symptoms, even after controlling for ADHD symptoms. Results from segregation analyses were consistent with primary findings, underscoring the significance of internetwork iFC interactions for autism symptom severity across diagnoses. No statistically significant brain-behavior relationships were observed for ADHD symptoms. Genetic enrichment analyses of the iFC maps associated with autism symptoms implicated genes known to: (i) have greater rate of variance in autism and ADHD, and (ii) be involved in neuron projection, suggesting shared genetic mechanisms for this specific brain-clinical phenotype. Overall, these findings underscore the relevance of transdiagnostic dimensional approaches in linking clinically-defined phenomena to shared presentations at the macroscale circuit- and genomic-levels among children with diagnoses of autism and ADHD.