Impacts of early social experience on cognitive development in infant rhesus macaques.

Although much is known about the influences of early life experiences on the neurobiology and behavior of macaque models of child development, there is scant literature on cognitive development with respect to early rearing. Here, we examined the effects of rearing condition on affective reactivity and cognitive development in infant rhesus macaques. Infants were pseudo-randomly assigned to one of the two rearing conditions: nursery reared (NR, N = 32; 16 peer-reared, 16 surrogate-peer-reared) or mother-peer-reared (MPR, N = 7). During the first month of life, infants were administered the Primate Neonatal Neurobehavioral Assessment (PNNA). Beginning at 4 months old, infants were tested on cognitive tasks that assessed reward association, cognitive flexibility, and impulsivity. We found no gross cognitive differences between MPR and NR infants. However, MPR infants were more reactive than NR infants on the PNNA. Additionally, reactivity on the PNNA correlated with impulsivity, such that infants who were more reactive at 1 month of age completed fewer trials correctly on this task at 8-10 months. These findings are the first to directly compare cognitive development in MPR and NR infants, and add to the existing literature elucidating the influences of early social experience on temperament and development.

DNA vaccination before conception protects Zika virus-exposed pregnant macaques against prolonged viremia and improves fetal outcomes.

Zika virus (ZIKV) infection of pregnant women is associated with congenital Zika syndrome (CZS) and no vaccine is available, although several are being tested in clinical trials. We tested the efficacy of ZIKV DNA vaccine VRC5283 in a rhesus macaque model of congenital ZIKV infection. Most animal vaccine experiments have a set pathogen exposure several weeks or months after vaccination. In the real world, people encounter pathogens years or decades after vaccination, or may be repeatedly exposed if the virus is endemic. To more accurately mimic how this vaccine would be used, we immunized macaques before conception and then exposed them repeatedly to ZIKV during early and mid-gestation. In comparison to unimmunized animals, vaccinated animals had a significant reduction in peak magnitude and duration of maternal viremia, early fetal loss, fetal infection, and placental and fetal brain pathology. Vaccine-induced neutralizing antibody titers on the day of first ZIKV exposure were negatively associated with the magnitude of maternal viremia, and the absence of prolonged viremia was associated with better fetal outcomes. These data support further clinical development of ZIKV vaccine strategies to protect against negative fetal outcomes.

Noninvasive cardiac psychophysiology as a tool for translational science with marmosets.

The importance of marmosets for comparative and translational science has grown in recent years because of their relatively rapid development, birth cohorts of twins, family social structure, and genetic tractability. Despite this, they remain understudied in investigations of affective processes. In this methodological note, we establish the validity of using noninvasive commercially available equipment to record cardiac physiology and compute indices of autonomic nervous system activity-a major component of affective processes. Specifically, we recorded electrocardiogram and impedance cardiogram, from which we derived heart rate, respiration rate, measures of high-frequency heart rate variability (indices of parasympathetic autonomic nervous system activity), and ventricular contractility (an index of sympathetic autonomic nervous system activity). Our methods produced physiologically plausible data, and further, animals with increased heart rates during testing were also more reactive to isolation from their social partner and presentation of novel objects, though no relationship was observed between reactivity and specific indices of parasympathetic or sympathetic nervous system activity.

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.

Cortisol in Neonatal Mother's Milk Predicts Later Infant Social and Cognitive Functioning in Rhesus Monkeys.

Milk provides not only the building blocks for somatic development but also the hormonal signals that contribute to the biopsychological organization of the infant. Among mammals, glucocorticoids (GCs) in mother's milk have been associated with infant temperament. This study extended prior work to investigate rhesus monkey (Macaca mulatta) mother-infant dyads (N = 34) from birth through 8 months postpartum. Regression analysis revealed that cortisol concentrations in milk during the neonatal period predicted impulsivity on a cognitive task, but not global social behaviors, months later. During this time period, sex-differentiated social behavior emerged. For female infants, milk cortisol concentrations predicted total frequency of play. Collectively, these findings support and extend the "lactational programming" hypothesis on the impact of maternal-origin hormones ingested via milk.

Sex and rank affect how infant rhesus macaques look at faces.

We investigated how differences in infant sex and mothers' dominance status affect infant rhesus macaques' (Macaca mulatta) interest in visually exploring emotional facial expressions. Thirty-eight infants were presented with animated avatars of macaque facial expressions during the first month of life. Sons of high-ranking mothers looked more at faces, especially the eye region, than sons of low-ranking mothers, but no difference in looking duration was found for daughters. Males looked significantly more at eyes than females, but this effect was reversed in infants who were reared without mothers in a primate nursery facility. In addition, in mother-infant interactions, mothers of sons were more likely to gaze at their infant's face compared to mothers of daughters. Combined with previous research indicating that rhesus macaque mothers interact differently with infants based on their own rank and infant's sex, these results support the view that social experiences shape early face preferences in rhesus macaques.

Rank acquisition in rhesus macaque yearlings following permanent maternal separation: The importance of the social and physical environment.

Rank acquisition is a developmental milestone for young primates, but the processes by which primate yearlings attain social rank in the absence of the mother remain unclear. We studied 18 maternally reared yearling rhesus macaques (Macaca mulatta) that differed in their social and physical rearing environments. We found that early social experience and maternal rank, but not individual traits (weight, sex, age), predicted dominance acquisition in the new peer-only social group. Yearlings also used coalitions to reinforce the hierarchy, and social affiliation (play and grooming) was likely a product, rather than a determinant, of rank acquisition. Following relocation to a familiar environment, significant rank changes occurred indicating that familiarity with a physical environment was salient in rank acquisition. Our results add to the growing body of literature emphasizing the role of the social and physical environment on behavioral development, namely social asymmetries among peers.

Relationships between affiliative social behavior and hair cortisol concentrations in semi-free ranging rhesus monkeys.

Sociality is a fundamental aspect of human behavior and health. One benefit of affiliative social relationships is reduced short-term levels of glucocorticoids (GCs), which are indicative of physiological stress. Less is known, however, about chronic GC production in relation to affiliative social behavior. To address this issue, we studied a semi-free ranging troop of rhesus macaques (Macaca mulatta) and collected hair samples to measure hair cortisol concentrations (HCCs), as a measure of chronic GC production, during routine biannual exams. We collected social behavior (both aggressive and affiliative) and hair samples for 32 adult female rhesus macaques over one year (Experiment 1). Our results indicated that adult females who initiated higher levels of social affiliation had significantly lower levels of HCCs. Neither the initiation nor the receipt of aggression were significantly related to HCCs in this study. In a second experiment we studied 28 mother-infant dyads for the first 90days postpartum to examine mother-infant facial interactions (i.e. mutual gazing). We analyzed HCCs during weaning approximately one year later, which is a major transitional period. We found that infants that engaged in higher levels of mutual gazing in the first 90days postpartum had significantly lower levels of HCCs during weaning. Finally, we studied 17 infant rhesus macaques (13 males) to examine whether social behavior (such as play) in the first five months of life correlated with infant HCCs over those months (Experiment 3). We found that infant males that engaged in more social play had significantly lower levels of HCCs. By relying on an animal model, our study shows that affiliative social traits are associated with lower long-term GC production. Future research should address the complex interactions between social behavior, chronic GC production, and mental and physical health.

Neonatal face-to-face interactions promote later social behaviour in infant rhesus monkeys.

In primates, including humans, mothers engage in face-to-face interactions with their infants, with frequencies varying both within and across species. However, the impact of this variation in face-to-face interactions on infant social development is unclear. Here we report that infant monkeys (Macaca mulatta) who engaged in more neonatal face-to-face interactions with mothers have increased social interactions at 2 and 5 months. In a controlled experiment, we show that this effect is not due to physical contact alone: monkeys randomly assigned to receive additional neonatal face-to-face interactions (mutual gaze and intermittent lip-smacking) with human caregivers display increased social interest at 2 months, compared with monkeys who received only additional handling. These studies suggest that face-to-face interactions from birth promote young primate social interest and competency.

First-time rhesus monkey mothers, and mothers of sons, preferentially engage in face-to-face interactions with their infants.

Face-to-face interactions between mothers and infants occur in both human and non-human primates, but there is large variability in the occurrence of these behaviors and the reason for this variability remains largely unexplored. Other types of maternal investment have been shown to be dependent on infant sex (e.g. milk production and maternal responsiveness) and maternal experience (e.g. symmetrical communication). Thus, we sought to determine whether variability in face-to-face interactions, that is, mutual gazing (MG), which are hypothesized to be important for later socio-cognitive development, could be explained by these variables. We studied 28 semi-free ranging rhesus monkey (Macaca mulatta) mother-infant dyads (6 primiparous; 12 male infants) born and reared at the Laboratory of Comparative Ethology field station at the NIH Animal Center in Poolesville, MD, across the first 90 postnatal days. Infant sex (i.e. male) was a significant predictor of maternal grooming (ß ± SE = 0.359 ± 0.164, Z = 2.19, P = 0.029) whereas both parity (i.e. first time mothers) and infant sex (i.e. male) significantly predicted MG (parity: ß ± SE = -0.735 ± 0.223, Z = -3.30, P < 0.001; infant sex: ß ± SE = 0.436 ± 0.201, Z = 2.17, P = 0.029). Separation from the mother (outside of arm's reach) was not influenced by parity or infant sex. Together with existing literature, these findings point toward differential maternal investment for sons versus daughters. Mothers may be investing differentially in sons, behaviorally, to ensure their future social competence and thus later reproductive success. Collectively, our findings add to the literature that is beginning to identify early life experiences that may lead to sex differences in neurological and behavioral development.

Development of a cognitive testing apparatus for socially housed mother-peer-reared infant rhesus monkeys.

Though cognitive testing of infant monkeys has been practiced for the past 40 years, these assessments have been limited primarily to nursery-reared infants due to the confounds of separating mother-reared infants for assessments. Here, we describe a pilot study in which we developed a cognitive testing apparatus for socially housed, mother-peer-reared rhesus macaques under 1 year of age (Macaca mulatta) that allowed the infants to freely return to their mothers for contact comfort. Infants aged 151.2 ± 18.3 days (mean ± SEM; n = 5) were trained and tested on an object detour reach task. Infants completed training in 5.0 ± 0.2 days, and completed testing in 6.2 ± 0.9 days. Across 4 days of testing, infants improved to nearly errorless performance (Friedman test: χ(2) = 13.27, df = 3, p = 0.004) and learned to do the task more quickly (Friedman test: χ(2) = 11.69, df = 3, p = 0.009). These are the first cognitive data in group-housed, mother-peer-reared rhesus monkeys under 1 year of age, and they underscore the utility of this apparatus for studying cognitive development in a normative population of infant monkeys.