Newborn auditory brainstem response and sudden infant death syndrome.

Sudden infant death syndrome (SIDS)-the sudden and unexplained death of a seemingly healthy infant, <1 year old-may be associated with abnormalities in the brain regions that underlie breathing and arousal during sleep. While post-mortem studies suggest abnormalities in SIDS infants' brainstems, there are no studies of these infants' brainstem function before death. One way to assess the function of the brainstem is with auditory brainstem response (ABR), a routine hearing-screening method that noninvasively measures the brainstem's response to sound. We hypothesize that anomalies in newborns' ABR measures may predict SIDS. Indeed, previous studies identified abnormalities in ABR characteristics in small samples of near-miss SIDS infants hospitalized for infant apnea syndrome. However, there is a need to examine the ABRs of infants who died of SIDS. Therefore, in the current study, we propose integrating two secondary datasets to examine newborns' ABRs (N = 156,972), including those who later died of SIDS (n = ~42; .27 out of every 1000 infants), using existing archived records of neonatal ABR results from a sample of newborns born in Florida. We hypothesize that infants who die from SIDS are more likely than non-SIDS infants to have abnormal ABRs as newborns. Understanding the association between SIDS and ABR may facilitate more accurate identification of an infant's risk for SIDS at birth, enabling increased monitoring, which may facilitate interventions and improve survivorship.

Infants' salivary oxytocin and positive affective reactions to people.

Oxytocin is a neuropeptide positively associated with prosociality in adults. Here, we studied whether infants' salivary oxytocin can be reliably measured, is developmentally stable, and is linked to social behavior. We longitudinally collected saliva from 62 U.S. infants (44 % female, 56 % Hispanic/Latino, 24 % Black, 18 % non-Hispanic White, 11 % multiracial) at 4, 8, and 14 months of age and offline-video-coded the valence of their facial affect in response to a video of a smiling woman. We also captured infants' affective reactions in terms of excitement/joyfulness during a live, structured interaction with a singing woman in the Early Social Communication Scales at 14 months. We detected stable individual differences in infants' oxytocin levels over time (over minutes and months) and in infants' positive affect over months and across contexts (video-based and in live interactions). We detected no statistically significant changes in oxytocin levels between 4 and 8 months but found an increase from 8 to 14 months. Infants with higher oxytocin levels showed more positive facial affect to a smiling person video at 4 months; however, this association disappeared at 8 months, and reversed at 14 months (i.e., higher oxytocin was associated with less positive facial affect). Infant salivary oxytocin may be a reliable physiological measure of individual differences related to socio-emotional development.

Infection detection in faces: Children's development of pathogen avoidance.

This study examined the development of children's avoidance and recognition of sickness using face photos from people with natural, acute, contagious illness. In a U.S. sample of fifty-seven 4- to 5-year-olds (46% male, 70% White), fifty-two 8- to 9-year-olds (26% male, 62% White), and 51 adults (59% male, 61% White), children and adults avoided and recognized sick faces (ds ranged from 0.38 to 2.26). Both avoidance and recognition improved with age. Interestingly, 4- to 5-year-olds' avoidance of sick faces positively correlated with their recognition, suggesting stable individual differences in these emerging skills. Together, these findings are consistent with a hypothesized immature but functioning and flexible behavioral immune system emerging early in development. Characterizing children's sickness perception may help design interventions to improve health.

Validation of an open source, remote web-based eye-tracking method (WebGazer) for research in early childhood.

Measuring eye movements remotely via the participant's webcam promises to be an attractive methodological addition to in-person eye-tracking in the lab. However, there is a lack of systematic research comparing remote web-based eye-tracking with in-lab eye-tracking in young children. We report a multi-lab study that compared these two measures in an anticipatory looking task with toddlers using WebGazer.js and jsPsych. Results of our remotely tested sample of 18-27-month-old toddlers (N = 125) revealed that web-based eye-tracking successfully captured goal-based action predictions, although the proportion of the goal-directed anticipatory looking was lower compared to the in-lab sample (N = 70). As expected, attrition rate was substantially higher in the web-based (42%) than the in-lab sample (10%). Excluding trials based on visual inspection of the match of time-locked gaze coordinates and the participant's webcam video overlayed on the stimuli was an important preprocessing step to reduce noise in the data. We discuss the use of this remote web-based method in comparison with other current methodological innovations. Our study demonstrates that remote web-based eye-tracking can be a useful tool for testing toddlers, facilitating recruitment of larger and more diverse samples; a caveat to consider is the larger drop-out rate.

Maximizing valid eye-tracking data in human and macaque infants by optimizing calibration and adjusting areas of interest.

Remote eye tracking with automated corneal reflection provides insights into the emergence and development of cognitive, social, and emotional functions in human infants and non-human primates. However, because most eye-tracking systems were designed for use in human adults, the accuracy of eye-tracking data collected in other populations is unclear, as are potential approaches to minimize measurement error. For instance, data quality may differ across species or ages, which are necessary considerations for comparative and developmental studies. Here we examined how the calibration method and adjustments to areas of interest (AOIs) of the Tobii TX300 changed the mapping of fixations to AOIs in a cross-species longitudinal study. We tested humans (N = 119) at 2, 4, 6, 8, and 14 months of age and macaques (Macaca mulatta; N = 21) at 2 weeks, 3 weeks, and 6 months of age. In all groups, we found improvement in the proportion of AOI hits detected as the number of successful calibration points increased, suggesting calibration approaches with more points may be advantageous. Spatially enlarging and temporally prolonging AOIs increased the number of fixation-AOI mappings, suggesting improvements in capturing infants' gaze behaviors; however, these benefits varied across age groups and species, suggesting different parameters may be ideal, depending on the population studied. In sum, to maximize usable sessions and minimize measurement error, eye-tracking data collection and extraction approaches may need adjustments for the age groups and species studied. Doing so may make it easier to standardize and replicate eye-tracking research findings.

Behavioral and physiological sensitivity to natural sick faces.

The capacity to rapidly detect and avoid sick people may be adaptive. Given that faces are reliably available, as well as rapidly detected and processed, they may provide health information that influences social interaction. Prior studies used faces that were manipulated to appear sick (e.g., editing photos, inducing inflammatory response); however, responses to naturally sick faces remain largely unexplored. We tested whether adults detected subtle cues of genuine, acute, potentially contagious illness in face photos compared to the same individuals when healthy. We tracked illness symptoms and severity with the Sickness Questionnaire and Common Cold Questionnaire. We also checked that sick and healthy photos were matched on low-level features. We found that participants (N = 109) rated sick faces, compared to healthy faces, as sicker, more dangerous, and eliciting more unpleasant feelings. Participants (N = 90) rated sick faces as more likely to be avoided, more tired, and more negative in expression than healthy faces. In a passive-viewing eye-tracking task, participants (N = 50) looked longer at healthy than sick faces, especially the eye region, suggesting people may be more drawn to healthy conspecifics. When making approach-avoidance decisions, participants (N = 112) had greater pupil dilation to sick than healthy faces, and more pupil dilation was associated with greater avoidance, suggesting elevated arousal to threat. Across all experiments, participants' behaviors correlated with the degree of sickness, as reported by the face donors, suggesting a nuanced, fine-tuned sensitivity. Together, these findings suggest that humans may detect subtle threats of contagion from sick faces, which may facilitate illness avoidance. By better understanding how humans naturally avoid illness in conspecifics, we may identify what information is used and ultimately improve public health.

Social motivation predicts gaze following between 6 and 14 months.

Infants vary in their ability to follow others' gazes, but it is unclear how these individual differences emerge. We tested whether social motivation levels in early infancy predict later gaze following skills. We longitudinally tracked infants' (N = 82) gazes and pupil dilation while they observed videos of a woman looking into the camera simulating eye contact (i.e., mutual gaze) and then gazing toward one of two objects, at 2, 4, 6, 8, and 14 months of age. To improve measurement validity, we used confirmatory factor analysis to combine multiple observed measures to index the underlying constructs of social motivation and gaze following. Infants' social motivation-indexed by their speed of social orienting, duration of mutual gaze, and degree of pupil dilation during mutual gaze-was developmentally stable and positively predicted the development of gaze following-indexed by their proportion of time looking to the target object, first object look difference scores, and first face-to-object saccade difference scores-from 6 to 14 months of age. These findings suggest that infants' social motivation likely plays a role in the development of gaze following and highlight the use of a multi-measure approach to improve measurement sensitivity and validity in infancy research.

Infant temperamental fear, pupil dilation, and gaze aversion from smiling strangers.

In childhood, higher levels of temperamental fear-an early-emerging proclivity to distress in the face of novelty-are associated with lower social responsivity and greater social anxiety. While the early emergence of temperamental fear in infancy is poorly understood, it is theorized to be driven by individual differences in reactivity and self-regulation to novel stimuli. The current study used eye tracking to capture infants' (N = 124) reactions to a video of a smiling stranger-a common social encounter-including infant gaze aversions from the stranger's face (indexing arousal regulation) and pupil dilation (indexing physiological reactivity), longitudinally at 2, 4, 6, and 8 months of age. Multilevel mixed-effects models indicated that more fearful infants took more time to look away from a smiling stranger's face than less fearful infants, suggesting that high-fear infants may have slower arousal regulation. At 2 and 4 months, more fearful infants also exhibited greater and faster pupil dilation before gaze aversions, consistent with greater physiological reactivity. Together, these findings suggest that individual differences in infants' gaze aversions and pupil dilation can index the development of fearful temperament in early infancy, facilitating the identification of, and interventions for, risk factors to social disruptions.

A Prediction Model for Positive Infant Meconium and Urine Drug Tests.

OBJECTIVE: This study aimed to determine the factors associated with positive infant drug screen and create a shortened screen and a prediction model. STUDY DESIGN: This is a retrospective cohort study of all infants who were tested for drugs of abuse from May 2012 through May 2014. The primary outcome was positive infant urine or meconium drug test. Multivariable logistic regression was used to identify independent risk factors. A combined screen was created, and test characteristics were analyzed. RESULTS: Among the 3,861 live births, a total of 804 infants underwent drug tests. Variables associated with having a positive infant test were (1) positive maternal urine test, (2) substance use during pregnancy, (3) ≤ one prenatal visit, and (4) remote substance abuse; each p-value was less than 0.0001. A model with an indicator for having at least one of these four predictors had a sensitivity of 94% and a specificity of 69%. Application of this screen to our population would have decreased drug testing by 57%. No infants had a positive urine drug test when their mother's urine drug test was negative. CONCLUSION: This simplified screen can guide clinical decision making for determining which infants should undergo drug testing. Infant urine drug tests may not be needed when a maternal drug test result is negative. KEY POINTS: · Many common drug screening criteria are not predictive.. · Four criteria predicted positive infant drug tests.. · No infant urine drug test is needed if the mother tests negative..

Improving the generalizability of infant psychological research: The ManyBabies model.

Yarkoni's analysis clearly articulates a number of concerns limiting the generalizability and explanatory power of psychological findings, many of which are compounded in infancy research. ManyBabies addresses these concerns via a radically collaborative, large-scale and open approach to research that is grounded in theory-building, committed to diversification, and focused on understanding sources of variation.

Superior Detection of Faces in Male Infants at 2 Months.

Females generally attend more to social information than males; however, little is known about the early development of these sex differences. With eye tracking, 2-month olds' (N = 101; 44 females) social orienting to faces was measured within four-item image arrays. Infants were more likely to detect human faces compared to objects, suggesting a functional face detection system. Unexpectedly, males looked longer at human faces than females, and only males looked faster and longer at human faces compared to objects. Females, in contrast, looked less at human faces relative to animal faces and objects, appearing socially disinterested. Notably, this is the first report of a male face detection advantage at any age. These findings suggest a unique stage in early infant social development.

Face detection in 2- to 6-month-old infants is influenced by gaze direction and species.

Humans detect faces efficiently from a young age. Face detection is critical for infants to identify and learn from relevant social stimuli in their environments. Faces with eye contact are an especially salient stimulus, and attention to the eyes in infancy is linked to the emergence of later sociality. Despite the importance of both of these early social skills-attending to faces and attending to the eyes-surprisingly little is known about how they interact. We used eye tracking to explore whether eye contact influences infants' face detection. Longitudinally, we examined 2-, 4-, and 6-month-olds' (N = 65) visual scanning of complex image arrays with human and animal faces varying in eye contact and head orientation. Across all ages, infants displayed superior detection of faces with eye contact; however, this effect varied as a function of species and head orientation. Infants were more attentive to human than animal faces and were more sensitive to eye and head orientation for human faces compared to animal faces. Unexpectedly, human faces with both averted heads and eyes received the most attention. This pattern may reflect the early emergence of gaze following-the ability to look where another individual looks-which begins to develop around this age. Infants may be especially interested in averted gaze faces, providing early scaffolding for joint attention. This study represents the first investigation to document infants' attention patterns to faces systematically varying in their attentional states. Together, these findings suggest that infants develop early, specialized functional conspecific face detection.

Early rearing history influences oxytocin receptor epigenetic regulation in rhesus macaques.

Adaptations to stress can occur through epigenetic processes and may be a conduit for informing offspring of environmental challenge. We employed ChIP-sequencing for H3K4me3 to examine effects of early maternal deprivation (peer-rearing, PR) in archived rhesus macaque hippocampal samples (male, n = 13). Focusing on genes with roles in stress response and behavior, we assessed the effects of rearing on H3K4me3 binding by ANOVA. We found decreased H3K4me3 binding at genes critical to behavioral stress response, the most robust being the oxytocin receptor gene OXTR, for which we observed a corresponding decrease in RNA expression. Based on this finding, we performed behavioral analyses to determine whether a gain-of-function nonsynonymous OXTR SNP interacted with early stress to influence relevant behavioral stress reactivity phenotypes (n = 194), revealing that this SNP partially rescued the PR phenotype. PR infants exhibited higher levels of separation anxiety and arousal in response to social separation, but infants carrying the alternative OXTR allele did not exhibit as great a separation response. These data indicate that the oxytocin system is involved in social-separation response and suggest that epigenetic down-modulation of OXTR could contribute to behavioral differences observed in PR animals. Epigenetic changes at OXTR may represent predictive adaptive responses that could impart readiness to respond to environmental challenge or maintain proximity to a caregiver but also contribute to behavioral pathology. Our data also demonstrate that OXTR polymorphism can permit animals to partially overcome the detrimental effects of early maternal deprivation, which could have translational implications for human psychiatric disorders.

Human and monkey infant attention to dynamic social and nonsocial stimuli.

The present study explored behavioral norms for infant social attention in typically developing human and nonhuman primate infants. We examined the normative development of attention to dynamic social and nonsocial stimuli longitudinally in macaques (Macaca mulatta) at 1, 3, and 5 months of age (N = 75) and humans at 2, 4, 6, 8, and 13 months of age (N = 69) using eye tracking. All infants viewed concurrently played silent videos-one social video and one nonsocial video. Both macaque and human infants were faster to look to the social than the nonsocial stimulus, and both species grew faster to orient to the social stimulus with age. Further, macaque infants' social attention increased linearly from 1 to 5 months. In contrast, human infants displayed a nonlinear pattern of social interest, with initially greater attention to the social stimulus, followed by a period of greater interest in the nonsocial stimulus, and then a rise in social interest from 6 to 13 months. Overall, human infants looked longer than macaque infants, suggesting humans have more sustained attention in the first year of life. These findings highlight potential species similarities and differences, and reflect a first step in establishing baseline patterns of early social attention development.

Interindividual differences in neonatal sociality and emotionality predict juvenile social status in rhesus monkeys.

In humans, socioeconomic status (SES) has profound outcomes on socio-emotional development and health. However, while much is known about the consequences of SES, little research has examined the predictors of SES due to the longitudinal nature of such studies. We sought to explore whether interindividual differences in neonatal sociality, temperament, and early social experiences predicted juvenile social status in rhesus monkeys (Macaca mulatta), as a proxy for SES in humans. We performed neonatal imitation tests in infants' first week of life and emotional reactivity assessments at 2 and 4 weeks of age. We examined whether these traits, as well as the rearing environment in the first 8 months of life (with the mother or with same-aged peers only) and maternal social status predicted juvenile (2-3 years old) social status following the formation of peer social groups at 8 months. We found that infants who exhibited higher rates of neonatal imitation and newborn emotional reactivity achieved higher social status as juveniles, as did infants who were reared with their mothers, compared to infants reared with peers. Maternal social status was only associated with juvenile status for infant dyads reared in the same maternal group, indicating that relative social relationships were transferred through social experience. These results suggest that neonatal imitation and emotional reactivity may reflect ingrained predispositions toward sociality that predict later outcomes, and that nonnormative social experiences can alter socio-developmental trajectories. Our results indicate that neonatal characteristics and early social experiences predict later social outcomes in adolescence, including gradients of social stratification.

Face detection in infants and adults: Effects of orientation and color.

Humans rapidly locate and recognize human faces, even in complex environments. In the current study, we explored some of the social and perceptual features of faces that may contribute to this ability. We measured infant and adult attention to complex, heterogeneous image arrays containing human and animal faces. Arrays were upright or inverted 180° and in color or grayscale. Infants, aged 3-5 months (n = 51) and 10-11 months (n = 34), viewed 6-item arrays (Experiment 1), whereas adults (n = 120) searched 64-item arrays (Experiment 2). We found that 3- to 5-month-olds already displayed strong own-species biases in face detection-in attention capture, attention holding, and overall detection-suggesting a surprisingly early specialization for human face detection. Furthermore, this remarkable ability was robust, evident even when color and orientation were disrupted, and grew stronger with age. Interestingly, infants' face detection was reduced by low-level manipulations in a species-specific way, negatively affecting only animal face detection but not affecting human face detection. In contrast, adults' face detection efficiency was equally reduced by low-level manipulations across species, suggesting potential age differences in own-species face detection. For infants, social relevance (species) may play a more important role than low-level perceptual features, ensuring that infants attend to, connect with, and learn from the people around them. Efficient human face detection during infancy may reflect the uniqueness of own-species faces as a category, perhaps due to their social relevance.

Visual preferences for direct-gaze faces in infant macaques (Macaca mulatta) with limited face exposure.

From birth, human and nonhuman primates attend more to faces with direct gaze compared with averted gaze, and previous studies report that attention to the eyes is linked to the emergence of later social skills. Here, we explored whether early experiences influence attraction to eye contact in infant macaques by examining their attention to face pairs varying in their gaze direction across the first 13 weeks of life. Infants raised by human caretakers had limited conspecific interactions (nursery-reared; N = 16) and were compared to infants raised in rich social environments (mother-reared; N = 20). Both groups looked longer to faces and the eyes of direct compared to averted-gaze faces. Looking to all faces and eyes also increased with age. Nursery-reared infants did not display age-associated increases in attention to direct-gaze faces specifically, suggesting that, while there may be an initial preference for direct-gaze faces from birth, social experiences may support its early development.

Who's my little monkey? Effects of infant-directed speech on visual retention in infant rhesus macaques.

Both human and nonhuman primate adults use infant-directed facial and vocal expressions across many contexts when interacting with infants (e.g., feeding, playing). This infant-oriented style of communication, known as infant-directed speech (IDS), seems to benefit human infants in numerous ways, including facilitating language acquisition. Given the variety of contexts in which adults use IDS, we hypothesized that IDS supports learning beyond the linguistic domain and that these benefits may extend to nonhuman primates. We exposed 2.5-month-old rhesus macaque infants (N = 15) to IDS, adult-directed speech (ADS), and a non-social control (CTR) during a video presentation of unrelated stimuli. After a 5- or 60-minute delay, infants were shown the familiar video side-by-side with a novel video. Infants exhibited a novelty preference after the 5-minute delay, but not after the 60-minute delay, in the ADS and CTR conditions, and a novelty preference in the IDS condition only after the 60-minute delay. These results are the first to suggest that exposure to IDS affects infants' long-term memory, even in non-linguistic animals.

Face Detection and the Development of Own-Species Bias in Infant Macaques.

In visually complex environments, numerous items compete for attention. Infants may exhibit attentional efficiency-privileged detection, attention capture, and holding-for face-like stimuli. However, it remains unknown when these biases develop and what role, if any, experience plays in this emerging skill. Here, nursery-reared infant macaques' (Macaca mulatta; n = 10) attention to faces in 10-item arrays of nonfaces was measured using eye tracking. With limited face experience, 3-week-old monkeys were more likely to detect faces and looked longer at faces compared to nonfaces, suggesting a robust face detection system. By 3 months, after peer exposure, infants looked faster to conspecific faces but not heterospecific faces, suggesting an own-species bias in face attention capture, consistent with perceptual attunement.

Inhaled oxytocin increases positive social behaviors in newborn macaques.

Early caregiver-infant interactions are critical for infants' socioemotional and cognitive development. Several hormones and neuromodulators, including oxytocin, affect these interactions. Exogenous oxytocin promotes social behaviors in several species, including human and nonhuman primates. Although exogenous oxytocin increases social function in adults--including expression recognition and affiliation--it is unknown whether oxytocin can increase social interactions in infants. We hypothesized that nebulized oxytocin would increase affiliative social behaviors and such effects would be modulated by infants' social skills, measured earlier in development. We also hypothesized that oxytocin's effects on social behaviors may be due to its anxiolytic effects. We tested these hypotheses in a blind study by nebulizing 7- to 14-d-old macaques (n = 28) with oxytocin or saline. Following oxytocin administration, infants' facial gesturing at a human caregiver increased, and infants' salivary oxytocin was positively correlated with the time spent in close proximity to a caregiver. Infants' imitative skill (measured earlier in development: 1-7 d of age) predicted oxytocin-associated increases in affiliative behaviors--lip smacking, visual attention to a caregiver, and time in close proximity to a caregiver--suggesting that infants with higher propensities for positive social interactions are more sensitive to exogenous oxytocin. Oxytocin also decreased salivary cortisol, but not stress-related behaviors (e.g., scratching), suggesting the possibility of some anxiolytic effects. To our knowledge, this study provides the first evidence that oxytocin increases positive social behaviors in newborns. This information is of critical importance for potential interventions aimed at ameliorating inadequate social behaviors in infants with higher likelihood of developing neurodevelopmental disorder.