infant

Baby Toolbox Training and Certification Program

PROJECT SUMMARY Our objective is to improve early childhood outcomes and support the expansion of the NIH Infant and Toddler Toolbox (Baby Toolbox) by providing comprehensive training support to those interested in using it. The Baby Toolbox is a brand new, nationally-normed assessment for infants 1-42 months, commissioned by NICHD and released for public use in 2025. The Baby Toolbox is administered entirely on an iPad and includes 35 measures across six domains using novel technology (e.g., gaze tracking, automatic scoring, computerized adaptive testing). It has the potential to bring harmonization to the developmental fields, but in order for it to become a common currency for developmental research as envisioned, researchers need to know how to administer it and how to train others to administer it. We propose an education program that will include a week-long training workshop, certification activities, and post-workshop support to create expert cohorts of Baby Toolbox test administrators. Individuals who attend the workshops can become certified test trainers, capable of training others at their home institutions to administer the assessment thus creating a self-sufficient training model. Through the proposed educational program, we will provide funding to cover lodging, meals, and incidentals during the workshop, in addition to subsidizing transportation to/from the workshop and provide a one-year subscription to the Baby Toolbox. A portion of slots will also be set aside for those without current grant funding. Our team is highly qualified to complete these tasks because we have led the effort to develop the Baby Toolbox assessment and have already completed multiple training workshops for contract deliverables. This grant would continue the efforts started by the NICHD in funding the Baby Toolbox by helping support its rollout, implementation, and growth. To meet these goals, we have the following aims: Aim 1: Create cohorts of trained Baby Toolbox examiners who can catapult the Baby Toolbox into widespread use by hosting a comprehensive week-long education program (training workshop) yearly for individuals to learn how to administer and train others to administer the Baby Toolbox, Aim 2: Expand the use of the Baby Toolbox by recruiting and financially supporting individuals who will bring the Baby Toolbox into a variety of research and clinical settings. Aim 3: Build a virtual training resource of videos and materials to support ongoing fidelity checks with certified trainers, and future training efforts.

Factory-treated, long-lasting permethrin baby wraps for the prevention of malaria: A phase III randomized controlled trial

PROJECT SUMMARY/ABSTRACT Progress against malaria has stalled. Novel interventions – particularly those targeting outdoor and daytime biting – are needed. In a randomized, placebo-controlled trial of permethrin- vs. sham-treated baby wraps in Uganda, we found a significant reduction in clinical malaria incidence among children carried in permethrin- as compared to sham-treated wraps (Boyce et al, NEJM, 2025). Despite these promising results, our trial incorporated a monthly re-treatment strategy that would be difficult to operationalize at scale. Furthermore, we only followed participants for 6 months, which is shorter than the expected period of use. Therefore, implementation studies - and specifically trials of long-lasting, factory-treated textiles - are now needed. Factory-treated materials would not only eliminate the need for retreatment for up to 12 months, but because the chemicals are more tightly bound, result in less absorption across the skin. Therefore, we now propose to conduct a randomized, double-blind trial of factory-treated, long-lasting (FTLL) wraps. AIM 1: Determine the effectiveness of FTLL permethrin wraps in combination with existing interventions for the prevention of malaria in children. We will enroll 750 mother-infant pairs from routine immunization visits (~3 months of age) at 3 sites of varying transmission intensity across Uganda. All participants will receive new dual active ingredient (AI) bed nets and be randomized (1:1) to either FTLL or untreated wraps. The primary outcome will be clinical malaria incidence during the period of wrap use, defined as fever a positive malaria rapid diagnostic test (RDT) between the FTLL and untreated arms. AIM 2: Confirm the safety of extended exposure to FTLL permethrin wraps for use in young children. Although a review of factory-treated clothing by the US Environmental Protection Agency, including clothing for children and toddlers, did not identify scenarios of concern, the frequency of use envisioned here may be beyond that modeled. To accomplish this, we will perform semi-annual assessments of growth (e.g., height-for-weight) and neurodevelopment (ND) during the period of use and 12-months after discontinuation. AIM 3: Assess the effect of FTLL permethrin wraps on Anopheles mosquito indices and blood-meal seeking behaviors. We will conduct longitudinal entomological surveillance, including CDC-light trap and aspirator collections, supplemented by human landing catches at sentinel households (~10-15%) from both the FTLL and untreated arms. This work tests a novel intervention, which leverages technology developed by the US military, to reduce the burden of malaria in endemic countries. Addressing malaria in these countries minimizes the risk of importation into the US. If successful, the project will provide additional evidence for treated textiles, which may be used to protect American travelers and deployed military servicemembers. The project will be conducted in Uganda, where malaria is highly endemic and it will be possible to enroll at-risk women-infant pairs.

Perturbation of mammary immunoglobulins during maternal antibiotic administration

Project Summary Prescribed in up to 40% of pregnancies, antibiotics represent the most commonly used class of medication during pregnancy. Although this practice is often necessary for maternal health, accumulating evidence suggests that antibiotic exposure may have unintended consequences for the mother-infant dyad. Epidemiologic studies associate maternal antibiotic exposure, especially in the absence of infection, with increased risk of neonatal complications including late-onset sepsis (LOS) and necrotizing enterocolitis (NEC), yet the mechanisms driving these associations remain poorly understood. Secretory IgA (sIgA) in milk is an essential component of neonatal mucosal immunity, shaping early gut microbial colonization and providing protection against enteric pathogens. The mechanisms by which maternal physiology regulates the abundance and microbial specificity of these antibodies in milk remain poorly understood. In animal models, the maternal gut–mammary axis governs the generation of milk IgA: IgA-committed lymphocytes from the maternal intestine migrate to the mammary gland during advancing pregnancy via CCL- 28/CCR10 signaling. Our preliminary data suggest that maternal antibiotic exposure disrupts this process leading to a decrease in milk IgA. However, the timing and extent of antibody dysbiosis are undefined; the downstream effects on neonatal intestinal health are unknown; and the underlying mechanisms—whether due to altered microbial stimulation, impaired recruitment of IgA⁺ cells to the mammary gland, or both—remain to be elucidated. Our central hypothesis is that maternal antibiotic exposure reduces pathogen-reactive IgA in milk by impairing gut-to-mammary immune cell trafficking thereby compromising neonatal mucosal immunity and increasing infection susceptibility. We will address this hypothesis through three integrated aims: (1) Determine the magnitude and duration of antibiotic-mediated mammary antibody dysbiosis in women who deliver preterm and at term; (2) Identify microbial targets of mammary antibodies diminished by maternal antibiotic exposure and (3 Determine the role of maternal antibiotics in the disruption of mammary resident IgA+ plasma cells in animal models. This integrative human and animal study will uncover critical mechanisms by which maternal antibiotic use alters the maternal-infant immune axis. The results will provide mechanistic insight into the risks associated with perinatal antibiotic exposure and inform clinical strategies to mitigate risk to neonatal health.

Systems Biology of Early Atopy: Role of Human Milk (SunBEAm-Milk)

Surprisingly little is known about the effect of breastfeeding (BF) on infant immune system development besides an effect on the gut microbiome, but its impact on metabolites and Tregs could support protection against food allergy (FA). BF is currently recommended to prevent the development of allergic diseases, especially asthma/recurrent wheezing and AD in early childhood, but firm conclusions could not be drawn regarding FA due to high heterogeneity and low quality of studies. Reverse causation, recall bias and the poor accuracy of outcome assessment are significant limitations. Most are inadequately powered to specific FA; however, a recent study showed that exclusively BF infants had lower odds of egg, sesame, and peanut allergies. Importantly, immunomodulatory composition of HM varies between mothers, which has not been taken into consideration. For over two decades we have been developing methods to assess immunomodulatory factors in the complex matrix of HM and their association with infant FA. We have shown that high levels of HM total and specific IgA are associated with protection against cow’s milk allergy, but it is unclear whether HM IgA is responsible for or is a biomarker of the vertical transfer of protection. Infant fecal and systemic IgA levels during breastfeeding and after weaning are also elevated in infants at low risk for atopic disease raising the question of whether HM factors such as cytokines can promote IgA production in infants. Consistent with this, we showed that HM cytokines, such as APRIL, induce IgA production in naïve infant B cells, and infants receiving HM with higher levels of APRIL had lower incidence of allergic disease. Finally, lower levels of several HM fatty acids including short-chain fatty acids and DHA were associated with FA. While some these factors were are associated with maternal atopic disease, several of them are not and suggest a role for diet instead. The System Biology of Early Atopy (SunBEAm) population-based cohort of 2500 mother-infant pairs is >50% recruited and provides an unprecedented opportunity to assess association of HM feeding and immune factors in HM with development of infant immune system and FA/AD. The Common Sample comprises a subset of 100 dyads with FA, 100 with FA+AD, 100 with AD, 100 with no FA or AD and more extensively profiled biological data. Utilizing all 2-month HM samples available in the Common Sample, we will assess levels of immune factors in HM and their association with maternal/infant characteristics (Aim 1). Utilizing data from the whole cohort, we will assess the association between HM vs formula feeding on well-defined FA/AD further adjusted based on high vs low levels of HM immune components in the Common Sample (Aim 2b). Finally, we will examine the immune cell and epithelial effects of HM on infant immune markers and intestinal organoids (Aim 3). Key findings will be validated in an independent birth cohort. The ultimate goal is to uncover protective properties of BF and HM in FA and subsequent design of policies and prevention strategies to address the increasing rates of FA.

Maternal Depression and Antidepressant Effects on Fetal Brain Structure and Function (FABMOMS)

PROJECT ABSTRACT Major depressive disorder (MDD) is one of the most common diseases in childbearing women, with a prevalence of 12.7% in pregnancy and 21.9% the year after birth. Exposure to maternal stress and depressive symptoms alters fetal/infant neurodevelopment, functional brain connectivity, and networks implicated in stress processing. About 5% of pregnant women are prescribed a serotonin selective or serotonin norepinephrine reuptake inhibitor (collectively, SRI). Remission of maternal MDD is crucial to the health and functioning of the mother and family. In observational studies typical of this field, differentiating the effects of drug exposure on offspring from the sequelae of the underlying psychiatric disease, both physiological and psychosocial, is challenging. Substantial progress has been made using sophisticated study designs and analytic approaches with large pregnancy cohorts that reduce the risk of spurious associations. Increased rates of overall and cardiac defects, stillbirth, preterm birth, and fetal growth have been largely explained by confounding by factors associated with both MDD and these outcomes rather than SRI exposure. Assessing the neurobehavioral development of children exposed in utero to SRI is the current research priority in this field. Our team pioneered the development of novel and safe fetal and neonatal quantitative magnetic resonance imaging (qMRI) tools, which will be combined with an evaluation of maternal heart rate variability to explore associations between exposures to stress, psychiatric symptoms and SRI on fetal and neonatal brain structure and function. The overarching goal of this project is to evaluate the separate and interactive effects of exposure to antidepressants in utero and maternal MDD on fetal and infant brain structure and function, with a specific focus on the hippocampus. We will accomplish this by evaluating four groups of pregnant women who have: 1) MDD treated with SRI to remission), 2) MDD treated with SRI (non-remitted, with both depressive symptom and SRI exposure), 3) MDD untreated with antidepressants, and 4) no current MDD or SRI treatment. Maternal assessments will occur at intake and in the early third trimesters and in then newborn period (at the time of fetal/newborn MRI) after birth. Maternal and infant evaluations will continue at 6 and 12 months postpartum. Maternal psychosocial and psychiatric status will provide extensive data on the context in which mothers experience pregnancy and infant care and allow adjustment for factors that will inevitably differ across groups. Lastly, we will explore the effects of maternal choline on MDD and offspring brain development. As these exposures and neurodevelopmental studies are conducted, exploring primary preventive strategies is a public health imperative. We will explore a potential mediator, poor maternal choline intake, a modifiable risk factor for both maternal MDD and altered fetal hippocampal growth and infant neurobehavior.

Programming Offspring Metabolism: The Role of Milk Extracellular Vesicles in Fat Development

SUMMARY Obesity is a global health crisis, contributing significantly to the prevalence of metabolic disorders, cardiovascular diseases, and various chronic conditions. A growing body of evidence suggests that maternal obesity during pregnancy and lactation can predispose offspring to obesity and metabolic dysfunction later in life. However, the mechanisms by which maternal obesity programs these adverse outcomes in offspring remain poorly understood. Breast milk is not only a source of essential nutrients but also contains bioactive components, including extracellular vesicles (EVs), which play crucial roles in cellular communication and development. Recent studies have shown that EVs can survive digestion and enter the infant’s circulation, influencing immune and metabolic development. Despite the established link between maternal obesity and altered breast milk composition, no study has investigated the role of milk-derived EVs (mEVs) in programming offspring fat development and metabolism. Understanding this novel pathway could revolutionize our approach to preventing intergenerational transmission of obesity. Our preliminary studies using a mouse model of maternal high-fat diet-induced obesity revealed significant alterations in mEV biogenesis and cargo composition, including changes in specific miRNAs. Oral administration of mEVs from obese dams to neonatal mice increased adiposity and impaired lipid metabolism, indicating that mEVs are crucial in modulating fat development and metabolic pathways in offspring. Several key miRNAs found in mouse mEVs are conserved in human milk EVs, highlighting the potential translational relevance of our findings to human health. We hypothesize that mEVs are critical mediators of maternal obesity’s programming effects on offspring metabolism and adiposity. In specific aim 1, we will use mouse models and advanced molecular techniques (miRNA sequencing, proteomics, and lipidomics) to characterize how maternal obesity affects mEV biogenesis and the composition of their bioactive cargo. We will also evaluate how maternal dietary intake, independent of obesity, influences mEV composition. Specific aim 2 will define the programming effects of mEVs on offspring energy metabolism and obesity. In addition, we will explore whether human milk EVs from lean and obese mothers exert similar programming effects on fat development and metabolism in a mouse model. This R21 application embodies a high-risk, high-reward approach to obesity research. It ventures into uncharted territory by proposing that mEVs are novel regulators of metabolic programming, a concept that has not been explored in prior studies. The potential reward is substantial: discovering a new mechanism by which maternal obesity influences offspring health could fundamentally shift our understanding of early-life metabolic programming and lead to innovative strategies for obesity prevention. If successful, this research could open a new field of study with broad implications for maternal and child health.

Addressing C-F bonds and amyloid-formation in biological systems

The ingestion, pulmonary inhalation, and dermal infiltration of C-F bond-containing compounds, most commonly found in the form of per- and polyfluoroalkyl organic acids, causes oxidative stress, inflammation, DNA damage, and developmental defects in infants and adults. These chemicals accumulate in the brain, disrupt neurological function and compromise cognitive and locomotory behavior. Yet, we lack a high-resolution road-map of the interactions between C-F bonds and biomolecular assemblies driving the trajectory towards neurodegenerative outcomes. This gap constitutes a significant barrier to advancing measures designed to mitigate C-F chemistry-associated neurotoxicity. Emerging experimental and computational data from our laboratory reveals that perfluorooctanoic acid, perfluorodecanoic acid and perfluorosulfonic acid corrupt biomolecular structures through C-F:side-chain interactions in tested soluble, globular proteins found in milk and tissues (matrices where C-F chemistries have been detected). Furthermore, they impaired the physiological function in these proteins through displacement of physiological ligands or by compromising the binding of co-factors. The neuroblastoma-derived SHSY-5Y cell line insulted with the said C-F moieties displayed altered gene expression corresponding to reactive oxygen species (ROS), protein ubiquitination, inflammation along with compromised cytoskeletal integrity. C-F bond ingestion ablated dopaminergic (DA) neurons in the nematode C. elegans and induced locomotory deficits in a manner mimicking paraquat. Based on these findings, we propose to gather data towards our hypothesis that C-F bond exposure perturbs biomolecular, cellular and organismal assemblies to onset neurodegeneration-linked trajectories. In Aim 1, we will determine whether organic fluoroacids alter mRNA levels in differentiated SHSY-5Y cells and in neuroprotective gut bacteria (Lactobacillus rhamnosus, Bifidobacterium lactis and Lactobacillus acidophilus). We will examine whether the neuroblastoma cell line exposed to C-F chemistry displays readouts designed to inform the onset of neurodegeneration-associated trajectories (including α-synuclein aggregation). In Aim 2, we will further address in a preclinical model whether C-F burden induces protein aggregation (α-synuclein, amyloid β, mHTT), interferes with dopaminergic neuronal assembles and induces locomotory deficits. Completion of the proposed work will complement ongoing experimental biophysical, structural (crystallographic, NMR) and computational (docking, molecular dynamics simulations) mapping of the interactions between these anthropogenic “forever” chemicals and amyloid-forming proteins potentially resulting in a soluble-to-toxic transformation. It will prepare the stage for vertebrate testing. The findings from this relatively understudied area likely exposes interventional targets for C-F chemistry associated neurotoxicity, spurs therapeutic efforts and can also guide the development of more biocompatible alternatives.

Stability in disrupted maternal representations over the perinatal period: Contributors and consequences

Abstract High-quality mother-infant relationships promote social, emotional, and cognitive development while protecting against poor child behavioral, health, and psychological adaptation that create risk for long- term negative outcomes. As mothers transition to parenthood, their own experiences of being cared for influence their emerging views of parenting and representations of their developing child. Evidence suggests that ‘disrupted’ maternal representations of the child, i.e., representations characterized by mixed communication, role merging, extreme withdrawal, and other unusual psychological processes, are tied to both poor child socioemotional adjustment and both insecure and disorganized attachment. However, it is unclear whether disrupted representations that emerge during pregnancy remain stable across the first several years of the child’s life. In addition, to date, research has not examined how change/stability in these representations may affect maternal caregiving and subsequent child adaptation. Using data from a longitudinal, multi-method study, this proposed project will examine the stability of maternal representations of the child for 99 women living in high risk contexts using the Working Model of the Child Interview during the third trimester and again when the child is two years of age. Mothers’ demographic characteristics (i.e. SES and relationship status), interpersonal violence experiences (i.e. child maltreatment or intimate violence exposure), psychological health (i.e. depressive, anxious, and PTSD symptoms), and parenting stress (i.e. perceptions of the child as difficult and parent-child interactions as dysfunctional) are measured as well to examine influences on representation stability. Finally, the observed quality of maternal caregiving and child adaptation are measured and examined in relation to stability in maternal representations of the child. Findings from this study have the potential to identify which mother-child dyads are at greatest risk for poor adaptation across the perinatal period and to delineate the contributors and consequences of maternal representational stability. These findings will serve as an important step towards informing the development or modification of existing prevention/intervention approaches that are targeted specifically towards mother-child dyads who are most at need.

Characterization of biofilm formation in shigellosis

Abstract The intestinal pathogen Shigella flexneri is the causative agent of bacillary dysentery and is responsible for more than 250 million cases of dysentery annually, resulting in more than 200,000 deaths. S. flexneri is an intracellular pathogen that invade epithelial cells in the colon and spread from cell to cell. The dissemination process relies on a bacterial adaptor termed IcsA that recruits key components of the actin cytoskeleton and supports actin-based motility. We have recently discovered that in addition of its intracellular role in dissemination, IcsA also support bile salt-dependent biofilm formation. Here, we propose to characterize the structural determinants that support IcsA-mediated bile salts-dependent biofilm formation (Aim1) and the role of IcsA in extracellular and intracellular colonization in an infant rabbit model of shigellosis (Aim2). The characterization of the dual functions of IcsA will provide novel insights into the mechanisms supporting bacillary dysentery in humans.

The reinstatement of a forgotten infantile memory

From Spiking Predictive Coding to Learning Abstract Object Representation

In a first part of the talk, I will present Predictive Coding Light (PCL), a novel unsupervised learning architecture for spiking neural networks. In contrast to conventional predictive coding approaches, which only transmit prediction errors to higher processing stages, PCL learns inhibitory lateral and top-down connectivity to suppress the most predictable spikes and passes a compressed representation of the input to higher processing stages. We show that PCL reproduces a range of biological findings and exhibits a favorable tradeoff between energy consumption and downstream classification performance on challenging benchmarks. A second part of the talk will feature our lab’s efforts to explain how infants and toddlers might learn abstract object representations without supervision. I will present deep learning models that exploit the temporal and multimodal structure of their sensory inputs to learn representations of individual objects, object categories, or abstract super-categories such as „kitchen object“ in a fully unsupervised fashion. These models offer a parsimonious account of how abstract semantic knowledge may be rooted in children's embodied first-person experiences.

Dyslexia, Rhythm, Language and the Developing Brain

Recent insights from auditory neuroscience provide a new perspective on how the brain encodes speech. Using these recent insights, I will provide an overview of key factors underpinning individual differences in children’s development of language and phonology, providing a context for exploring atypical reading development (dyslexia). Children with dyslexia are relatively insensitive to acoustic cues related to speech rhythm patterns. This lack of rhythmic sensitivity is related to the atypical neural encoding of rhythm patterns in speech by the brain. I will describe our recent data from infants as well as children, demonstrating developmental continuity in the key neural variables.

Consciousness in the cradle: on the emergence of infant experience

Although each of us was once a baby, infant consciousness remains mysterious and there is no received view about when, and in what form, consciousness first emerges. Some theorists defend a ‘late-onset’ view, suggesting that consciousness requires cognitive capacities which are unlikely to be in place before the child’s first birthday at the very earliest. Other theorists defend an ‘early-onset’ account, suggesting that consciousness is likely to be in place at birth (or shortly after) and may even arise during the third trimester. Progress in this field has been difficult, not just because of the challenges associated with procuring the relevant behavioral and neural data, but also because of uncertainty about how best to study consciousness in the absence of the capacity for verbal report or intentional behavior. This review examines both the empirical and methodological progress in this field, arguing that recent research points in favor of early-onset accounts of the emergence of consciousness.

Vision Unveiled: Understanding Face Perception in Children Treated for Congenital Blindness

Despite her still poor visual acuity and minimal visual experience, a 2-3 month old baby will reliably respond to facial expressions, smiling back at her caretaker or older sibling. But what if that same baby had been deprived of her early visual experience? Will she be able to appropriately respond to seemingly mundane interactions, such as a peer’s facial expression, if she begins seeing at the age of 10? My work is part of Project Prakash, a dual humanitarian/scientific mission to identify and treat curably blind children in India and then study how their brain learns to make sense of the visual world when their visual journey begins late in life. In my talk, I will give a brief overview of Project Prakash, and present findings from one of my primary lines of research: plasticity of face perception with late sight onset. Specifically, I will discuss a mixed methods effort to probe and explain the differential windows of plasticity that we find across different aspects of distributed face recognition, from distinguishing a face from a nonface early in the developmental trajectory, to recognizing facial expressions, identifying individuals, and even identifying one’s own caretaker. I will draw connections between our empirical findings and our recent theoretical work hypothesizing that children with late sight onset may suffer persistent face identification difficulties because of the unusual acuity progression they experience relative to typically developing infants. Finally, time permitting, I will point to potential implications of our findings in supporting newly-sighted children as they transition back into society and school, given that their needs and possibilities significantly change upon the introduction of vision into their lives.

Internal representation of musical rhythm: transformation from sound to periodic beat

When listening to music, humans readily perceive and move along with a periodic beat. Critically, perception of a periodic beat is commonly elicited by rhythmic stimuli with physical features arranged in a way that is not strictly periodic. Hence, beat perception must capitalize on mechanisms that transform stimulus features into a temporally recurrent format with emphasized beat periodicity. Here, I will present a line of work that aims to clarify the nature and neural basis of this transformation. In these studies, electrophysiological activity was recorded as participants listened to rhythms known to induce perception of a consistent beat across healthy Western adults. The results show that the human brain selectively emphasizes beat representation when it is not acoustically prominent in the stimulus, and this transformation (i) can be captured non-invasively using surface EEG in adult participants, (ii) is already in place in 5- to 6-month-old infants, and (iii) cannot be fully explained by subcortical auditory nonlinearities. Moreover, as revealed by human intracerebral recordings, a prominent beat representation emerges already in the primary auditory cortex. Finally, electrophysiological recordings from the auditory cortex of a rhesus monkey show a significant enhancement of beat periodicities in this area, similar to humans. Taken together, these findings indicate an early, general auditory cortical stage of processing by which rhythmic inputs are rendered more temporally recurrent than they are in reality. Already present in non-human primates and human infants, this "periodized" default format could then be shaped by higher-level associative sensory-motor areas and guide movement in individuals with strongly coupled auditory and motor systems. Together, this highlights the multiplicity of neural processes supporting coordinated musical behaviors widely observed across human cultures.The experiments herein include: a motor timing task comparing the effects of movement vs non-movement with and without feedback (Exp. 1A & 1B), a transcranial magnetic stimulation (TMS) study on the role of the supplementary motor area (SMA) in transforming temporal information (Exp. 2), and a perceptual timing task investigating the effect of noisy movement on time perception with both visual and auditory modalities (Exp. 3A & 3B). Together, the results of these studies support the Bayesian cue combination framework, in that: movement improves the precision of time perception not only in perceptual timing tasks but also motor timing tasks (Exp. 1A & 1B), stimulating the SMA appears to disrupt the transformation of temporal information (Exp. 2), and when movement becomes unreliable or noisy there is no longer an improvement in precision of time perception (Exp. 3A & 3B). Although there is support for the proposed framework, more studies (i.e., fMRI, TMS, EEG, etc.) need to be conducted in order to better understand where and how this may be instantiated in the brain; however, this work provides a starting point to better understanding the intrinsic connection between time and movement

Epigenetic rewiring in Schinzel-Giedion syndrome

During life, a variety of specialized cells arise to grant the right and timely corrected functions of tissues and organs. Regulation of chromatin in defining specialized genomic regions (e.g. enhancers) plays a key role in developmental transitions from progenitors into cell lineages. These enhancers, properly topologically positioned in 3D space, ultimately guide the transcriptional programs. It is becoming clear that several pathologies converge in differential enhancer usage with respect to physiological situations. However, why some regulatory regions are physiologically preferred, while some others can emerge in certain conditions, including other fate decisions or diseases, remains obscure. Schinzel-Giedion syndrome (SGS) is a rare disease with symptoms such as severe developmental delay, congenital malformations, progressive brain atrophy, intractable seizures, and infantile death. SGS is caused by mutations in the SETBP1 gene that results in its accumulation further leading to the downstream accumulation of SET. The oncoprotein SET has been found as part of the histone chaperone complex INHAT that blocks the activity of histone acetyltransferases suggesting that SGS may (i) represent a natural model of alternative chromatin regulation and (ii) offer chances to study downstream (mal)adaptive mechanisms. I will present our work on the characterization of SGS in appropriate experimental models including iPSC-derived cultures and mouse.

A mind set in stone: fossil traces of human brain evolution

Brains do not fossilise, but as they grow and expand during fetal and infant development, they leave an imprint in the bony braincase. Such imprints of fossilised braincases provide direct evidence of brain evolution, but the underlying biological changes have remained elusive. Combining data from fossil skulls, ancient genomes, brain imaging and gene expression helps shed light on the evolutionary changes shaping the human brain. I will highlight two examples separated by more than 3 million years: the evolution of brain growth in Lucy and her kind, and differences between modern humans and Neanderthals.

Children’s inference of verb meanings: Inductive, analogical and abductive inference

Children need inference in order to learn the meanings of words. They must infer the referent from the situation in which a target word is said. Furthermore, to be able to use the word in other situations, they also need to infer what other referents the word can be generalized to. As verbs refer to relations between arguments, verb learning requires relational analogical inference, something which is challenging to young children. To overcome this difficulty, young children recruit a diverse range of cues in their inference of verb meanings, including, but not limited to, syntactic cues and social and pragmatic cues as well as statistical cues. They also utilize perceptual similarity (object similarity) in progressive alignment to extract relational verb meanings and further to gain insights about relational verb meanings. However, just having a list of these cues is not useful: the cues must be selected, combined, and coordinated to produce the optimal interpretation in a particular context. This process involves abductive reasoning, similar to what scientists do to form hypotheses from a range of facts or evidence. In this talk, I discuss how children use a chain of inferences to learn meanings of verbs. I consider not only the process of analogical mapping and progressive alignment, but also how children use abductive inference to find the source of analogy and gain insights into the general principles underlying verb learning. I also present recent findings from my laboratory that show that prelinguistic human infants use a rudimentary form of abductive reasoning, which enables the first step of word learning.

Do Capuchin Monkeys, Chimpanzees and Children form Overhypotheses from Minimal Input? A Hierarchical Bayesian Modelling Approach

Abstract concepts are a powerful tool to store information efficiently and to make wide-ranging predictions in new situations based on sparse data. Whereas looking-time studies point towards an early emergence of this ability in human infancy, other paradigms like the relational match to sample task often show a failure to detect abstract concepts like same and different until the late preschool years. Similarly, non-human animals have difficulties solving those tasks and often succeed only after long training regimes. Given the huge influence of small task modifications, there is an ongoing debate about the conclusiveness of these findings for the development and phylogenetic distribution of abstract reasoning abilities. Here, we applied the concept of “overhypotheses” which is well known in the infant and cognitive modeling literature to study the capabilities of 3 to 5-year-old children, chimpanzees, and capuchin monkeys in a unified and more ecologically valid task design. In a series of studies, participants themselves sampled reward items from multiple containers or witnessed the sampling process. Only when they detected the abstract pattern governing the reward distributions within and across containers, they could optimally guide their behavior and maximize the reward outcome in a novel test situation. We compared each species’ performance to the predictions of a probabilistic hierarchical Bayesian model capable of forming overhypotheses at a first and second level of abstraction and adapted to their species-specific reward preferences.

Development of multisensory perception and attention and their role in audiovisual speech processing

Dancing to a Different Tune: TANGO Gives Hope for Dravet Syndrome

The long-term goal of our research is to understand the mechanisms of SUDEP, defined as Sudden, Unexpected, witnessed or unwitnessed, nontraumatic and non-drowning Death in patients with EPilepsy, excluding cases of documented status epilepticus. The majority of SUDEP patients die during sleep. SUDEP is the most devastating consequence of epilepsy, yet little is understood about its causes and no biomarkers exist to identify at risk patients. While SUDEP accounts for 7.5-20% of all epilepsy deaths, SUDEP risk in the genetic epilepsies varies with affected genes. Patients with ion channel gene variants have the highest SUDEP risk. Indirect evidence variably links SUDEP to seizure-induced apnea, pulmonary edema, dysregulation of cerebral circulation, autonomic dysfunction, and cardiac arrhythmias. Arrhythmias may be primary or secondary to hormonal or metabolic changes, or autonomic discharges. When SUDEP is compared to Sudden Cardiac Death secondary to Long QT Syndrome, especially to LQT3 linked to variants in the voltage-gated sodium channel (VGSC) gene SCN5A, there are parallels in the circumstances of death. To gain insight into SUDEP mechanisms, our approach has focused on channelopathies with high SUDEP incidence. One such disorder is Dravet syndrome (DS), a devastating form of developmental and epileptic encephalopathy (DEE) characterized by multiple pharmacoresistant seizure types, intellectual disability, ataxia, and increased mortality. While all patients with epilepsy are at risk for SUDEP, DS patients may have the highest risk, up to 20%, with a mean age at SUDEP of 4.6 years. Over 80% of DS is caused by de novo heterozygous loss-of-function (LOF) variants in SCN1A, encoding the VGSC Nav1.1  subunit, resulting in haploinsufficiency. A smaller cohort of patients with DS or a more severe DEE have inherited, homozygous LOF variants in SCN1B, encoding the VGSC 1/1B non-pore-forming subunits. A related DEE, Early Infantile EE (EIEE) type 13, is linked to de novo heterozygous gain-of-function variants in SCN8A, encoding the VGSC Nav1.6. VGSCs underlie the rising phase and propagation of action potentials in neurons and cardiac myocytes. SCN1A, SCN8A, and SCN1B are expressed in both the heart and brain of humans and mice. Because of this, we proposed that cardiac arrhythmias contribute to the mechanism of SUDEP in DEE. We have taken a novel approach to the development of therapeutics for DS in collaboration with Stoke Therapeutics. We employed Targeted Augmentation of Nuclear Gene Output (TANGO) technology, which modulates naturally occurring, non-productive splicing events to increase target gene and protein expression and ameliorate disease phenotype in a mouse model. We identified antisense oligonucleotides (ASOs) that specifically increase the expression of productive Scn1a transcript in human and mouse cell lines, as well as in mouse brain. We showed that a single intracerebroventricular dose of a lead ASO at postnatal day 2 or 14 reduced the incidence of electrographic seizures and SUDEP in the F1:129S-Scn1a+/- x C57BL/6J mouse model of DS. Increased expression of productive Scn1a transcript and NaV1.1 protein were confirmed in brains of treated mice. Our results suggest that TANGO may provide a unique, gene-specific approach for the treatment of DS.

Pediatric Migraine: Who, What, When, Where

This talk will address important aspects of pediatric migraine research, including: 1) Who is affected by pediatric migraine? 2) What does pediatric migraine look like, and what does a clinician need to do to reach a migraine diagnosis in a child? 3) When does pediatric migraine begin, and how might it present clinically before it presents as headache (e.g., infant colic, benign paroxysmal torticollis, cyclic vomiting syndrome etc.) 4) Where does responsibility for decreasing pediatric migraine frequency rest? What is society's role in preventing migraine in young people?

Sleepless in Vienna - how to rescue folding-deficient dopamine transporters by pharmacochaperoning

Diseases that arise from misfolding of an individual protein are rare. However, collectively, these folding diseases represent a large proportion of hereditary and acquired disorders. In fact, the term "Molecular Medicine" was coined by Linus Pauling in conjunction with the study of a folding disease, i.e. sickle cell anemia. In the past decade, we have witnessed an exponential growth in the number of mutations, which have been identified in genes encoding solute carriers (SLC). A sizable faction - presumably the majority - of these mutations result in misfolding of the encoded protein. While studying the export of the GABA transporter (SLC6A1) and of the serotonin transporter (SLC6A4), from the endoplasmic reticulum (ER), we discovered by serendipity that some ligands can correct the folding defect imparted by point mutations. These bind to the inward facing state. The most effective compound is noribogaine, the metabolite of ibogaine (an alkaloid first isolated from the shrub Tabernanthe iboga). There are 13 mutations in the human dopamine transporter (DAT, SLC6A3), which give rise to a syndrome of infantile Parkinsonism and dystonia. We capitalized on our insights to explore, if the disease-relevant mutant proteins were amenable to pharmacological correction. Drosopohila melanogaster, which lack the dopamine transporter, are hyperactive and sleepless (fumin in Japanese). Thus, mutated human DAT variants can be introduced into fumin flies. This allows for examining the effect of pharmacochaperones on delivery of DAT to the axonal territory and on restoring sleep. We explored the chemical space populated by variations of the ibogaine structure to identify an analogue (referred to as compound 9b), which was highly effective: compound 9b also restored folding in DAT variants, which were not amenable to rescue by noribogaine. Deficiencies in the human creatine transporter-1 (CrT1, SLC6A8) give rise to a syndrome of intellectual disability and seizures and accounts for 5% of genetically based intellectual disabilities in boys. Point mutations occur, in part, at positions, which are homologous to those of folding-deficient DAT variants. CrT1 lacks the rich pharmacology of monoamine transporters. Nevertheless, our insights are also applicable to rescuing some disease-related variants of CrT1. Finally, the question arises how one can address the folding problem. We propose a two-pronged approach: (i) analyzing the effect of mutations on the transport cycle by electrophysiological recordings; this allows for extracting information on the rates of conformational transitions. The underlying assumption posits that - even when remedied by pharmacochaperoning - folding-deficient mutants must differ in the conformational transitions associated with the transport cycle. (ii) analyzing the effect of mutations on the two components of protein stability, i.e. thermodynamic and kinetic stability. This is expected to provide a glimpse of the energy landscape, which governs the folding trajectory.

Representations of abstract relations in infancy

Abstract relations are considered the pinnacle of human cognition, allowing analogical and logical reasoning, and possibly setting humans apart from other animal species. Such relations cannot be represented in a perceptual code but can easily be represented in a propositional language of thought, where relations between objects are represented by abstract discrete symbols. Focusing on the abstract relations same and different, I will show that (1) there is a discontinuity along ontogeny with respect to the representations of abstract relations, but (2) young infants already possess representations of same and different. Finally, (3) I will investigate the format of representation of abstract relations in young infants, arguing that those representations are not discrete, but rather built by juxtaposing abstract representations of entities.

SCN1A/Nav1.1 sodium channel: loss and gain of function in epilepsy and migraine

Genetic mutations of the SCN1A gene, the voltage gated sodium channel NaV1.1, cause well-defined epilepsies, including the severe developmental and epileptic encephalopathy Dravet syndrome and genetic epilepsy with febrile seizures plus (GEFS+), as well as a severe form of migraine with aura, familial hemiplegic migraine (FHM). More recently, they have been identified in an extremely severe early infantile encephalopathy. Functional studies and animal models have contributed to disclose pathological mechanisms, which can be often linked to a straightforward loss- vs gain- of channel function. However, although this simple dichotomy is pertinent and useful, detailed pathological mechanisms in neuronal circuits can be more complex, sometimes because of unexpected homeostatic or pathologic responses. I will compare pathological mechanisms of epilepsy and migraine mutations studied with cellular, animal and computational models, highlighting a novel homeostatic response implemented by CCK-positive GABAergic neurons in a mouse model of Dravet syndrome, which may be boosted in therapeutic approaches.

The retrotrapezoid nucleus: an integrative and interoceptive hub in neural control of breathing

In this presentation, we will discuss the cellular and molecular properties of the retrotrapezoid nucleus (RTN), an integrative and interoceptive control node for the respiratory motor system. We will present the molecular profiling that has allowed definitive identification of a cluster of tonically active neurons that provide a requisite drive to the respiratory central pattern generator (CPG) and other pre-motor neurons. We will discuss the ionic basis for steady pacemaker-like firing, including by a large subthreshold oscillation; and for neuromodulatory influences on RTN activity, including by arousal state-dependent neurotransmitters and CO2/H+. The CO2/H+-dependent modulation of RTN excitability represents the sensory component of a homeostatic system by which the brain regulates breathing to maintain blood gases and tissue pH; it relies on two intrinsic molecular proton detectors, both a proton-activated G protein-coupled receptor (GPR4) and a proton-inhibited background K+ channel (TASK-2). We will also discuss downstream neurotransmitter signaling to the respiratory CPG, focusing especially on a newly-identified peptidergic modulation of the preBötzinger complex that becomes activated following birth and the initiation of air breathing. Finally, we will suggest how the cellular and molecular properties of RTN neurons identified in rodent models may contribute to understanding human respiratory disorders, such as congenital central hypoventilation syndrome (CCHS) and sudden infant death syndrome (SIDS).

Role of Oxytocin in regulating microglia functions to prevent brain damage of the developing brain

Every year, 30 million infants worldwide are delivered after intra-uterine growth restriction (IUGR) and 15 million are born preterm. These two conditions are the leading causes of ante/perinatal stress and brain injury responsible for neurocognitive and behavioral disorders in more than 9 million children each year. Both prematurity and IUGR are associated with perinatal systemic inflammation, a key factor associated with neuroinflammation and identified to be the best predictor of subsequent neurological impairments. Most of pharmacological candidates have failed to demonstrate any beneficial effect to prevent perinatal brain damage. In contrast, environmental enrichment based on developmental care, skin-to-skin contact and vocal/music intervention appears to confer positive effects on brain structure and function. However, mechanisms underlying these effects remain unknown. There is strong evidence that an adverse environment during pregnancy and the perinatal period can influence hormonal responses of the newborn with long-lasting neurobehavioral consequences in infancy and adulthood. Excessive cortisol release in response to perinatal stress induces pro-inflammatory and brain-programming effects. These deleterious effects are known to be balanced by Oxytocin (OT), a neuropeptide playing a key role during the perinatal period and parturition, in social behavior and regulating the central inflammatory response to injury in the adult brain. Using a rodent model of IUGR associated with perinatal brain damage, we recently reported that Carbetocin, a brain permeable long-lasting OT receptor (OTR) agonist, was associated with a significant reduction of activated microglia, the primary immune cells of the brain. Moreover this reduced microglia reactivity was associated to a long-term neuroprotection. These findings make OT a promising candidate for neonatal neuroprotection through neuroinflammation regulation. However, the causality between the endogenous OT and central inflammation response to injury has not been established and will be further studied by the lab.

Assessing consciousness in human infants

In a few months, human infants develop complex capacities in numerous cognitive domains. They learn their native language, recognize their parents, refine their numerical capacities and their perception of the world around them but are they conscious and how can we study consciousness when no verbal report is possible? One way to approach this question is to rely on the neural responses correlated with conscious perception in adults (i.e. a global increase of activity in notably frontal regions with top-down amplification of the sensory levels). We can thus study at what age the developing anatomical architecture might be mature enough to allow this type of responses, but moreover we can use similar experimental paradigms than in adults in which we expect to observe a similar pattern of functional responses.

Vulnerable periods of brain development in ion channelopathies

Brain and neuronal network development depend on a complex sequence of events, which include neurogenesis, migration, differentiation, synaptogenesis, and synaptic pruning. Perturbations to any of these processes, for example associated with ion channel gene mutations (i.e., channelopathies), can underlie neurodevelopmental disorders such as neonatal and infantile epilepsies, strongly impair psychomotor development and cause persistent deficits in cognition, motor skills, or motor control. The therapeutic options available are very limited, and prophylactic therapies for patients at an increased risk of developing such epilepsies do not exist yet. By using genetic mouse models in which we controlled the activities of Kv7/M or HCN/h-channels during different developmental periods, we obtained offspring with distinct neurological phenotypes that could not simply be reversed by the re-introduction of the affected ion channel in juvenile or adult animals. The results indicate that channelopathy/mutation-specific treatments of neonatal and infantile epilepsies and their comorbidities need to be targeted to specific sensitive periods.

Social transmission of maternal behavior

Maternal care is profoundly important for mammalian survival, and in many species requires the contribution of non-biological parents, or alloparents. In the absence of partum and post-partum related hormonal changes, alloparents acquire maternal skills from experience, by yet unknown mechanisms. One critical molecular signal for maternal behavior is oxytocin, a hormone centrally released by hypothalamic paraventricular nucleus (PVN). Do experiences that induce maternal behavior act by engaging PVN oxytocin neurons? To answer this, we used virgin female mice, animals that in the wild live in colonies with experienced mothers and their pups, helping with pup care. We replicated this setup in the lab, and we continuously monitored homecage behavior of virgin mice co-housed for days with a mother and litter, synchronized with recordings from virgin PVN cells, including from oxytocin neurons. Mothers engaged virgins in maternal care in part by shepherding virgins towards the nest, ensuring their proximity to pups, and in part by self-generating pup retrieval episodes, demonstrating maternal behavior to virgins. The frequency of shepherding and of dam retrievals correlates with virgin's subsequent ability to retrieve pups, a quintessential mouse maternal skill. These social interactions activated virgin PVN and gated behaviorally-relevant cortical plasticity for pup vocalizations. Thus, rodents can acquire maternal behavior by social transmission, and our results describe a mechanism for adapting brains of adult caregivers to infant needs via endogenous oxytocin.

Preschoolers' Comprehension of Functional Metaphors

Previous work suggests that children’s ability to understand metaphors emerges late in development. Researchers argue that children’s initial failure to understand metaphors is due to an inability to reason about shared relational structures between concepts. However, recent work demonstrates that preschoolers, toddlers, and even infants are already capable of relational reasoning. Might preschoolers also be capable of understanding metaphors, given more sensitive experimental paradigms? I explore whether preschoolers (N = 200, ages 4-5) understand functional metaphors, namely metaphors based on functional similarities. In Experiment 1a, preschoolers rated functional metaphors (e.g. “Roofs are hats”; “Clouds are sponges”) as “smarter” than nonsense statements. In Experiment 1b, adults (N = 48) also rated functional metaphors as “smarter” than nonsense statements (e.g. “Dogs are scissors”; “Boats are skirts”). In Experiment 2, preschoolers preferred functional explanations (e.g. “Both hold water”) over perceptual explanations (e.g. “Both are fluffy”) when interpreting a functional metaphor (e.g. “Clouds are sponges”). In Experiment 3, preschoolers preferred functional metaphors over nonsense statements in a dichotomous-choice task. Overall, this work demonstrates preschoolers’ early-emerging ability to understand functional metaphors.

Becoming Human: A Theory of Ontogeny

Humans are biologically adapted for cultural life in ways that other primates are not. Humans have unique motivations and cognitive skills for sharing emotions, experience, and collaborative actions (shared intentionality). These motivations and skills first emerge in human ontogeny at around one year of age, as infants begin to participate with other persons in various kinds of collaborative and joint attentional activities, including linguistic communication. Our nearest primate relatives understand important aspects of intentional action - especially in competitive situations - but they do not seem to have the motivations and cognitive skills necessary to engage in activities involving collaboration, shared intentionality, and, in general, things cultural.

Infant Relational Learning - Interactions with Visual and Linguistic Factors

Humans are incredible learners, a talent supported by our ability to detect and transfer relational similarities between items and events. Spotting these common relations despite perceptual differences is challenging, yet there’s evidence that this ability begins early, with infants as young as 3 months discriminating same and different (Anderson et al., 2018; Ferry et al., 2015). How? To understand the underlying mechanisms, I examine how learning outcomes in the first year correspond with changes in input and in infant age. I discuss the commonalities in this process with that seen in older children and adults, as well as differences due to interactions with other maturing processes like language and visual attention.

The developing visual brain – answers and questions

We will start our talk with a short video of our research, illustrating methods (some old and new) and findings that have provided our current understanding of how visual capabilities develop in infancy and early childhood. However, our research poses some outstanding questions. We will briefly discuss three issues, which are linked by a common focus on the development of visual attentional processing: (1) How do recurrent cortical loops contribute to development? Cortical selectivity (e.g., to orientation, motion, and binocular disparity) develops in the early months of life. However, these systems are not purely feedforward but depend on parallel pathways, with recurrent feedback loops playing a critical role. The development of diverse networks, particularly for motion processing, may explain changes in dynamic responses and resolve developmental data obtained with different methodologies. One possible role for these loops is in top-down attentional control of visual processing. (2) Why do hyperopic infants become strabismic (cross-eyes)? Binocular interaction is a particularly sensitive area of development. Standard clinical accounts suppose that long-sighted (hyperopic) refractive errors require accommodative effort, putting stress on the accommodation-convergence link that leads to its breakdown and strabismus. Our large-scale population screening studies of 9-month infants question this: hyperopic infants are at higher risk of strabismus and impaired vision (amblyopia and impaired attention) but these hyperopic infants often under- rather than over-accommodate. This poor accommodation may reflect poor early attention processing, possibly a ‘soft sign’ of subtle cerebral dysfunction. (3) What do many neurodevelopmental disorders have in common? Despite similar cognitive demands, global motion perception is much more impaired than global static form across diverse neurodevelopmental disorders including Down and Williams Syndromes, Fragile-X, Autism, children with premature birth and infants with perinatal brain injury. These deficits in motion processing are associated with deficits in other dorsal stream functions such as visuo-motor co-ordination and attentional control, a cluster we have called ‘dorsal stream vulnerability’. However, our neuroimaging measures related to motion coherence in typically developing children suggest that the critical areas for individual differences in global motion sensitivity are not early motion-processing areas such as V5/MT, but downstream parietal and frontal areas for decision processes on motion signals. Although these brain networks may also underlie attentional and visuo-motor deficits , we still do not know when and how these deficits differ across different disorders and between individual children. Answering these questions provide necessary steps, not only increasing our scientific understanding of human visual brain development, but also in designing appropriate interventions to help each child achieve their full potential.

Cerebro Parental: La biología aun invisible del desarrollo infantil

Desde la investigación en antropología evolutiva, las neurociencias del comportamiento parental y los estudios de cohortes de orfelinatos, los nuevos conocimientos confluyen en la mayor importancia critica del periodo postnatal inmediato para el desarrollo social humano. Surge la explicación biológica de la interdependencia de los cambios comportamentales en los adultos que crían y el recién nacido: Nature of Nurture. Del concepto unidireccional clásico de la necesidad de estimular un cerebro inmaduro, se comienza a comprender la naturaleza de la interacción en red entre el cerebro neonatal y el cerebro parental que también debe ser estimulado. Concebir, engendra y criar son etapas sucesivas de la reproducción pero no indispensablemente continuas. La función parental es primariamente dependiente de la disponibilidad para cuidar al recién nacido.

Plasticity in hypothalamic circuits for oxytocin release

Mammalian babies are “sensory traps” for parents. Various sensory cues from the newborn are tremendously efficient in triggering parental responses in caregivers. We recently showed that core aspects of maternal behavior such as pup retrieval in response to infant vocalizations rely on active learning of auditory cues from pups facilitated by the neurohormone oxytocin (OT). Release of OT from the hypothalamus might thus help induce recognition of different infant cues but it is unknown what sensory stimuli can activate OT neurons. I performed unprecedented in vivo whole-cell and cell-attached recordings from optically-identified OT neurons in awake dams. I found that OT neurons, but not other hypothalamic cells, increased their firing rate after playback of pup distress vocalizations. Using anatomical tracing approaches and channelrhodopsin-assisted circuit mapping, I identified the projections and brain areas (including inferior colliculus, auditory cortex, and posterior intralaminar thalamus) relaying auditory information about social sounds to OT neurons. In hypothalamic brain slices, when optogenetically stimulating thalamic afferences to mimic high-frequency thalamic discharge, observed in vivo during pup calls playback, I found that thalamic activity led to long-term depression of synaptic inhibition in OT neurons. This was mediated by postsynaptic NMDARs-induced internalization of GABAARs. Therefore, persistent activation of OT neurons following pup calls in vivo is likely mediated by disinhibition. This gain modulation of OT neurons by infant cries, may be important for sustaining motivation. Using a genetically-encoded OT sensor, I demonstrated that pup calls were efficient in triggering OT release in downstream motivational areas. When thalamus projections to hypothalamus were inhibited with chemogenetics, dams exhibited longer latencies to retrieve crying pups, suggesting that the thalamus-hypothalamus noncanonical auditory pathway may be a specific circuit for the detection of social sounds, important for disinhibiting OT neurons, gating OT release in downstream brain areas, and speeding up maternal behavior.

Learning from the infant’s point of view

Learning depends on both the learning mechanism and the regularities in the training material, yet most research on human and machine learning focus on the discovering the mechanisms that underlie powerful learning. I will present evidence from our research focusing on the statistical structure of infant visual learning environments. The findings suggest that the statistical structure of those learning environments are not like those used in laboratory experiments on visual learning, in machine learning, or in our adult assumptions about how teach visual categories. The data derive from our use of head cameras and head-mounted eye trackers capturing FOV experiences in the home as well as in simulated home environments in the laboratory. The participants range from 1 month of age to 24 months. The observed statistical structure offers new insights into the developmental foundations of visual object recognition and suggest a computational rethinking of the problem of visual category formation. The observed environmental statistics also have direct implications for understanding the development of cortical visual systems.

Integration of infant sensory cues and internal states for maternal motivated behaviors

COSYNE 2022

Integration of infant sensory cues and internal states for maternal motivated behaviors

COSYNE 2022

Characterizing the functional maturation of the brain activity using resting-state EEG in premature infants

Early life attachment in term and preterm born infants

Endocrine Disrupting Chemicals in breastmilk and infant neurobehavioral development: The Life Milch project

Functional Manipulation of Infant Engram Expression

Maternal SARS CoV-2 infection during pregnancy and infant neurobehavior at 6-11 months

Oscillatory brain activity in infants during visual attention to dynamic faces and objects at the age of 11 months

Recent and remote spatial memory formation in infant and adult rats

Structural 3D modeling of VMAT2 mutants to improve diagnostic and therapeutic treatment of infantile Parkinsonism

Associations between maternal pre-pregnancy BMI and white matter integrity in infants

FENS Forum 2024

Behavioral correlates of parent-infant dyadic emotional synchrony and association with child socioemotional development

FENS Forum 2024

CYFIP2 Arg87Cys mutation: Unraveling its role in early infantile epileptic encephalopathy

FENS Forum 2024

Effects of over-activation of mTOR in the infant amygdala on its functionality at adolescence in rats

FENS Forum 2024

Engram competition modulates infant memory expression in development

FENS Forum 2024

Experience-dependent modulation of sensory inputs in the postpartum hypothalamus for infant-directed motor actions

FENS Forum 2024

Exploring the influence of maternal prenatal depressive symptoms and hair cortisol concentration on infant corpus callosum integrity

FENS Forum 2024

Infantile ceroid neuro-lipofuscinosis: Linking autophagy, altered chloride homeostasis, and enhanced brain excitability

FENS Forum 2024

Integration of hunger and hormonal state gates infant-directed aggression

FENS Forum 2024

Network mechanisms for the reinstatement of infant latent memories

FENS Forum 2024

The role of the mean diffusivity of the amygdala in the perception of emotional faces in 8-month-old infants

FENS Forum 2024

Role of the prefrontal cortex and nucleus accumbens in maternal and infanticidal behavior in naïve mice (C57BL6)

FENS Forum 2024