Faculty Bibliography

During the past decade, cognitive neuroscience has been calling for population diversity to address the challenge of validity and generalizability, ushering in a new era of population neuroscience. The developing Chinese Color Nest Project (devCCNP, 2013-2022), the first ten-year stage of the lifespan CCNP (2013-2032), is a two-stages project focusing on brain-mind development. The project aims to create and share a large-scale, longitudinal and multimodal dataset of typically developing children and adolescents (ages 6.0-17.9 at enrolment) in the Chinese population. The devCCNP houses not only phenotypes measured by demographic, biophysical, psychological and behavioural, cognitive, affective, and ocular-tracking assessments but also neurotypes measured with magnetic resonance imaging (MRI) of brain morphometry, resting-state function, naturalistic viewing function and diffusion structure. This Data Descriptor introduces the first data release of devCCNP including a total of 864 visits from 479 participants. Herein, we provided details of the experimental design, sampling strategies, and technical validation of the devCCNP resource. We demonstrate and discuss the potential of a multicohort longitudinal design to depict normative brain growth curves from the perspective of developmental population neuroscience. The devCCNP resource is shared as part of the "Chinese Data-sharing Warehouse for In-vivo Imaging Brain" in the Chinese Color Nest Project (CCNP) - Lifespan Brain-Mind Development Data Community ( https://ccnp.scidb.cn ) at the Science Data Bank.

The COVID-19 pandemic and resulting public health directives led to many changes in families' social and material environments. Prior research suggests that these changes are likely to impact composition of the gut microbiome, particularly during early childhood when the gut microbiome is developing most rapidly. Importantly, disruption to the gut microbiome during this sensitive period can have potentially long-lasting impacts on health and development. In the current study, we compare gut microbiome composition among a socioeconomically and racially diverse group of 12-month old infants living in New York City who provided stool samples before the pandemic (N = 34) to a group who provided samples during the first 9-months of the pandemic (March-December 2020; N = 20). We found that infants sampled during the pandemic had lower alpha diversity of the microbiome, lower abundance of Pasteurellaceae and Haemophilus, and significantly different beta diversity based on unweighted Unifrac distance than infants sampled before the pandemic. Exploratory analyses suggest that gut microbiome changes due to the pandemic occurred relatively quickly after the start of the pandemic and were sustained. Our results provide evidence that pandemic-related environmental disruptions had an impact on community-level taxonomic diversity of the developing gut microbiome, as well as abundance of specific members of the gut bacterial community.

HIGHLIGHTS/CONCLUSIONS:Interictal spikes (IIS) occur in 3 mouse lines with Alzheimer's disease featuresIIS in all 3 mouse lines were most frequent during rapid eye movement (REM) sleepThe dentate gyrus showed larger IIS and earlier current sources vs. CA1 or cortexChemogenetic silencing of medial septum (MS) cholinergic neurons reduced IIS during REMMS silencing did not change REM latency, duration, number of bouts or theta power. UNLABELLED:Interictal spikes (IIS) are a common type of abnormal electrical activity in Alzheimer's disease (AD) and preclinical models. The brain regions where IIS are largest are not known but are important because such data would suggest sites that contribute to IIS generation. Because hippocampus and cortex exhibit altered excitability in AD models, we asked which areas dominate the activity during IIS along the cortical-CA1-dentate gyrus (DG) dorso-ventral axis. Because medial septal (MS) cholinergic neurons are overactive when IIS typically occur, we also tested the novel hypothesis that silencing the MS cholinergic neurons selectively would reduce IIS.We used mice that simulate aspects of AD: Tg2576 mice, presenilin 2 (PS2) knockout mice and Ts65Dn mice. To selectively silence MS cholinergic neurons, Tg2576 mice were bred with choline-acetyltransferase (ChAT)-Cre mice and offspring were injected in the MS with AAV encoding inhibitory designer receptors exclusively activated by designer drugs (DREADDs). We recorded local field potentials along the cortical-CA1-DG axis using silicon probes during wakefulness, slow-wave sleep (SWS) and rapid eye movement (REM) sleep.We detected IIS in all transgenic or knockout mice but not age-matched controls. IIS were detectable throughout the cortical-CA1-DG axis and occurred primarily during REM sleep. In all 3 mouse lines, IIS amplitudes were significantly greater in the DG granule cell layer vs. CA1 pyramidal layer or overlying cortex. Current source density analysis showed robust and early current sources in the DG, and additional sources in CA1 and the cortex also. Selective chemogenetic silencing of MS cholinergic neurons significantly reduced IIS rate during REM sleep without affecting the overall duration, number of REM bouts, latency to REM sleep, or theta power during REM. Notably, two control interventions showed no effects.Consistent maximal amplitude and strong current sources of IIS in the DG suggest that the DG is remarkably active during IIS. In addition, selectively reducing MS cholinergic tone, at times when MS is hyperactive, could be a new strategy to reduce IIS in AD.

The Environmental Influences on Child Health Outcomes (ECHO)-Wide Cohort Study (EWC), a collaborative research design comprising 69 cohorts in 31 consortia, was funded by the National Institutes of Health (NIH) in 2016 to improve children's health in the United States. The EWC harmonizes extant data and collects new data using a standardized protocol, the ECHO-Wide Cohort Data Collection Protocol (EWCP). EWCP visits occur at least once per life stage, but the frequency and timing of the visits vary across cohorts. As of March 4, 2022, the EWC cohorts contributed data from 60,553 children and consented 29,622 children for new EWCP data and biospecimen collection. The median (interquartile range) age of EWCP-enrolled children was 7.5 years (3.7-11.1). Surveys, interviews, standardized examinations, laboratory analyses, and medical record abstraction are used to obtain information in 5 main outcome areas: pre-, peri-, and postnatal outcomes; neurodevelopment; obesity; airways; and positive health. Exposures include factors at the level of place (e.g., air pollution, neighborhood socioeconomic status), family (e.g., parental mental health), and individuals (e.g., diet, genomics).

OBJECTIVE:Because changes to pediatric emergency medicine (PEM) education may help address barriers to youth suicide risk screening programs, this study aimed to understand the impact of formal training in areas that likely include suicide-related practices, developmental-behavioral pediatrics (DBP) and adolescent medicine (AM), on PEM physician-perceived level of training, attitudes, and confidence assessing and managing youth suicide risk. METHODS:Twenty-seven PEM attendings and trainees completed an online survey and were divided into 2 groups: those who had completed DBP and AM rotations (DBP/AM+; n = 20) and those who had not completed either rotation (DBP/AM-; n = 7). We compared perceived level of training, attitudes, and confidence in assessing and managing suicide risk across groups. We also examined the relationship between perceived level of training and confidence. Finally, we conducted exploratory analyses to evaluate the effect of an additional formal rotation in child psychiatry. RESULTS:The DBP/AM+ and DBP/AM- groups did not differ on perceived level of training or on attitudes and confidence in suicide risk assessment or management. Perceived level of training in assessment and management predicted confidence in both assessing and managing suicide risk. Additional training in child psychiatry was not associated with increased perceived level of training or confidence. CONCLUSIONS:The DBP and AM rotations were not associated with higher perceived levels of suicide risk training or greater confidence; however, perceived level of training predicted physician confidence, suggesting continued efforts to enhance formal PEM education in mental health would be beneficial.

Chronic pain is a leading cause of disability, reduced productivity, healthcare seeking behavior, and a contributor to opioid overdose in the United States. For many people, pain can be satisfactorily managed by existing medicines and comprehensive psychosocial treatments. For others, available treatments are either ineffective or not acceptable, due to side effects and concerns about risks. Preliminary evidence suggests that some psychedelics may be effective for certain types of pain and/or improved quality of life with increased functionality and reduced disability and distress in people whose pain may never be completely relieved. Efficacy in these quality-of-life related outcomes would be consistent with the 'reset in thinking' about chronic pain management being increasingly called for as a more realistic goal for some people as compared to complete elimination of pain. This commentary summarizes the rationale for conducting more basic research and clinical trials to further explore the potential for psychedelics in chronic pain management. Additionally, if shown to be effective, to then determine whether the effects of psychedelics are primarily due to direct antinociceptive or anti-inflammatory mechanisms, or via increased tolerability, acceptance, and sense of spirituality, that appear to at least partially mediate the therapeutic effects of psychedelics observed in psychiatric disorders such as major depression. This commentary represents a collaboration of clinical and more basic scientists examining these issues and developing recommendations for research ranging from neuropharmacology to the biopsychosocial treatment factors that appear to be as important in pain management as in depression and other disorders in which psychedelic medicines are under development. This article is part of the Special Issue on "National Institutes of Health Psilocybin Research Speaker Series".

Infant survival relies on rapid identification, remembering and behavioral responsiveness to caregivers' sensory cues. While neural circuits supporting infant attachment learning have largely remained elusive in children, use of invasive techniques has uncovered some of its features in rodents. During a 10-day sensitive period from birth, newborn rodents associate maternal odors with maternal pleasant or noxious thermo-tactile stimulation, which gives rise to a preference and approach behavior towards these odors, and blockade of avoidance learning. Here we review the neural circuitry supporting this neonatal odor learning, unique compared to adults, focusing specifically on the early roles of neurotransmitters such as glutamate, GABA (Gamma-AminoButyric Acid), serotonin, dopamine and norepinephrine, in the olfactory bulb, the anterior piriform cortex and amygdala. The review highlights the importance of deepening our knowledge of age-specific infant brain neurotransmitters and behavioral functioning that can be translated to improve the well-being of children during typical development and aid in treatment during atypical development in childhood clinical practice, and the care during rearing of domestic animals.

There has been considerable speculation regarding the function of the dentate gyrus (DG) - a subregion of the mammalian hippocampus - in learning and memory. In this Perspective article, we compare leading theories of DG function. We note that these theories all critically rely on the generation of distinct patterns of activity in the region to signal differences between experiences and to reduce interference between memories. However, these theories are divided by the roles they attribute to the DG during learning and recall and by the contributions they ascribe to specific inputs or cell types within the DG. These differences influence the information that the DG is thought to impart to downstream structures. We work towards a holistic view of the role of DG in learning and memory by first developing three critical questions to foster a dialogue between the leading theories. We then evaluate the extent to which previous studies address our questions, highlight remaining areas of conflict, and suggest future experiments to bridge these theories.

OBJECTIVE:The dimensional model of adversity and psychopathology hypothesizes deprivation and threat impact distinct neurobiological pathways, such as brain structure. This hypothesis has not been examined longitudinally or in young children. We tested longitudinal associations between threat and deprivation measured in preschool and brain structure in childhood. We hypothesized threat would be associated with amygdala and hippocampal subcortical volume and deprivation would be associated with cortical thickness in association cortex. METHOD/METHODS:The study included T1-weighted scans from 72 children (5-10 years old, 54.2% female participants). Threat was measured by the presence of domestic violence, sexual abuse, physical abuse, or neighborhood violence. Deprivation was measured by the presence of neglect. We examined associations of deprivation or threat with brain structure controlling for other dimension (deprivation or threat) and nuisance covariates using whole-brain vertex-wise analyses. We extracted subcortical volume and examined the same associations using multiple regression. RESULTS:Threat was associated with widespread decreases in cortical surface area across the prefrontal cortex and other regions. Threat was not associated with amygdala or hippocampal volume. Deprivation was associated with increased thickness in occipital cortex, insula and cingulate. CONCLUSION/CONCLUSIONS:Results suggest distinct associations of deprivation and threat on brain structure in early childhood. Threat is associated with widespread differences in surface area and deprivation is associated with differences in cortical thickness. These observations are consistent with work in adolescence and adulthood and reflect how dimensions of adversity differentially impact neural structure.