Vocal labeling of others by nonhuman primates.

Humans, dolphins, and elephants are the only known species that vocally label their conspecifics. It remains unclear whether nonhuman primates share this ability. We recorded spontaneous "phee-call" dialogues between pairs of marmoset monkeys. We discovered that marmosets use these calls to vocally label their conspecifics. Moreover, they respond more consistently and correctly to calls that are specifically directed at them. Analysis of calls from multiple monkeys revealed that family members use similar calls and acoustic features to label others and perform vocal learning. These findings shed light on the complexities of social vocalizations among nonhuman primates and suggest that marmoset vocalizations may provide a model for understanding aspects of human language, thereby offering new insights into the evolution of social communication.

Cognitive development from infancy to young adulthood in common marmosets (Callithrix jacchus): Effect of age, sex, and hormones on learning and affective state.

Studies looking at individual variability in cognition have increased in recent years. We followed 43 marmosets (21 males, 22 females) from infancy to young adulthood. At 3-months old, marmosets were trained to touch a rewarded stimulus. At 9-, 15-, and 21-months old, they were given visual discrimination and cognitive bias tests, and urine samples were collected to examine hormone levels. Marmosets were significantly more successful learners at 15 months than 9 months. Individuals who were more successful learners at 9 months were also more successful at 15 months, with more male learners than expected at 15 months. At 9 months, learning success was associated with higher cortisol levels. At 15 months, males with higher estradiol levels were more successful learners, whereas at 21 months, females with higher estradiol and cortisol levels tended to be less successful learners and more pessimistic. Nine months, therefore, appears to be an important developmental timepoint for acquiring cognitive control, which has developed by 15 months. Steroids may have differential effects on each sex, with complex interactions between gonadal and adrenal hormones having an influence on cognitive function over the lifespan. This longitudinal study offers new insight into cognition, including its development and biological underpinnings.

Cross-modal representation of identity in the primate hippocampus.

Faces and voices are the dominant social signals used to recognize individuals among primates. Yet, it is not known how these signals are integrated into a cross-modal representation of individual identity in the primate brain. We discovered that, although single neurons in the marmoset hippocampus exhibited selective responses when presented with the face or voice of a specific individual, a parallel mechanism for representing the cross-modal identities for multiple individuals was evident within single neurons and at the population level. Manifold projections likewise showed the separability of individuals as well as clustering for others' families, which suggests that multiple learned social categories are encoded as related dimensions of identity in the hippocampus. Neural representations of identity in the hippocampus are thus both modality independent and reflect the primate social network.

Encoding identity in the marmoset.

Hippocampal cells integrate multisensory input to represent the identity of others.

Personality and social environment predict cognitive performance in common marmosets (Callithrix jacchus).

Consistent inter-individual variation in cognition has been increasingly explored in recent years in terms of its patterns, causes and consequences. One of its possible causes are consistent inter-individual differences in behaviour, also referred to as animal personalities, which are shaped by both the physical and the social environment. The latter is particularly relevant for group-living species like common marmosets (Callithrix jacchus), apt learners that display substantial variation in both their personality and cognitive performance, yet no study to date has interlinked these with marmosets' social environment. Here we investigated (i) consistency of learning speed, and (ii) whether the PCA-derived personality traits Exploration-Avoidance and Boldness-Shyness as well as the social environment (i.e., family group membership) are linked with marmosets' speed of learning. We tested 22 individuals in series of personality and learning-focused cognitive tests, including simple motor tasks and discrimination learning tasks. We found that these marmosets showed significant inter-individual consistency in learning across the different tasks, and that females learned faster than males. Further, bolder individuals, and particularly those belonging to certain family groups, learned faster. These findings indicate that both personality and social environment affect learning speed in marmosets and could be important factors driving individual variation in cognition.

Temporal consistency and ecological validity of personality structure in common marmosets (Callithrix jacchus): A unifying field and laboratory approach.

Personality in animals has been extensively researched in recent decades. Temporal consistency of behaviors is almost always part of the personality definition and is usually explored in several different testing sessions or observation periods. However, it is still unclear whether the obtained personality constructs are stable across several years, which might be especially important for long-living animals, such as primates. Further, little is known on whether the personality structures obtained in the laboratory reflect the structures obtained under ecologically relevant conditions in the wild. Therefore, we conducted a battery of personality tests on common marmosets (Callithrix jacchus) (N = 27), compared it with a test battery conducted 4 years beforehand on a subset of animals in captivity (N = 13) and ran an adapted version under field conditions at Baracuhy Biological Field Station, Brazil (N = 18). Under captive conditions, we found a remarkably similar personality structure across 4 testing years. Further, we found high long-term temporal consistency in the first two personality components, Boldness and Exploration; however, monkeys that changed their social (i.e., breeding) status between the two testing periods showed a significant increase in Boldness scores. Under field conditions, we found a somewhat similar personality structure as compared to the laboratory, which to some extent corroborates ecological validity of our personality test design. Nevertheless, whether the structure in the wild is suppressed or expanded in comparison to captivity, and in which way the social setting influences personality structure, should be further explored. Taken together, our results contribute to the discussion about the reliability and ecological validity of personality structures in nonhuman primates.

Higher social tolerance in wild versus captive common marmosets: the role of interdependence.

Social tolerance in a group reflects the balance between within-group competition and interdependence: whereas increased competition leads to a reduction in social tolerance, increased interdependence increases it. Captivity reduces both feeding competition and interdependence and can therefore affect social tolerance. In independently breeding primates, social tolerance has been shown to be higher in captivity, indicating a strong effect of food abundance. It is not known, however, how social tolerance in cooperative breeders, with their much higher interdependence, responds to captivity. Here, we therefore compared social tolerance between free-ranging and captive groups in the cooperatively breeding common marmoset and found higher social tolerance (measured as proximity near food, co-feeding, and food sharing) in the wild. Most likely, social tolerance in the wild is higher because interdependence is particularly high in the wild, especially because infant care is more costly there than in captivity. These results indicate that the high social tolerance of these cooperative breeders in captivity is not an artefact, and that captive data may even have underestimated it. They may also imply that the cooperative breeding and foraging of our hominin ancestors, which relied on strong interdependence at multiple levels, was associated with high social tolerance.

Over-activation of primate subgenual cingulate cortex enhances the cardiovascular, behavioral and neural responses to threat.

Stress-related disorders such as depression and anxiety are characterized by enhanced negative emotion and physiological dysfunction. Whilst elevated activity within area 25 of the subgenual anterior cingulate cortex (sgACC/25) has been implicated in these illnesses, it is unknown whether this over-activity is causal. By combining targeted intracerebral microinfusions with cardiovascular and behavioral monitoring in marmosets, we show that over-activation of sgACC/25 reduces vagal tone and heart rate variability, alters cortisol dynamics during stress and heightens reactivity to proximal and distal threat. 18F-FDG PET imaging shows these changes are accompanied by altered activity within a network of brain regions including the amygdala, hypothalamus and dorsolateral prefrontal cortex. Ketamine, shown to have rapid antidepressant effects, fails to reverse elevated arousal to distal threat contrary to the beneficial effects we have previously demonstrated on over-activation induced reward blunting, illustrating the symptom-specificity of its actions.

Robustness of sex-differences in functional connectivity over time in middle-aged marmosets.

Nonhuman primates (NHPs) are an essential research model for gaining a comprehensive understanding of the neural mechanisms of neurocognitive aging in our own species. In the present study, we used resting state functional connectivity (rsFC) to investigate the relationship between prefrontal cortical and striatal neural interactions, and cognitive flexibility, in unanaesthetized common marmosets (Callithrix jacchus) at two time points during late middle age (8 months apart, similar to a span of 5-6 years in humans). Based on our previous findings, we also determine the reproducibility of connectivity measures over the course of 8 months, particularly previously observed sex differences in rsFC. Male marmosets exhibited remarkably similar patterns of stronger functional connectivity relative to females and greater cognitive flexibility between the two imaging time points. Network analysis revealed that the consistent sex differences in connectivity and related cognitive associations were characterized by greater node strength and/or degree values in several prefrontal, premotor and temporal regions, as well as stronger intra PFC connectivity, in males compared to females. The current study supports the existence of robust sex differences in prefrontal and striatal resting state networks that may contribute to differences in cognitive function and offers insight on the neural systems that may be compromised in cognitive aging and age-related conditions such as mild cognitive impairment and Alzheimer's disease.

Early learning in the common marmoset (Callithrix jacchus): Behavior in the family group is related to preadolescent cognitive performance.

Early environment can have a major impact on development, with family life known to play an important role. Longitudinal studies can therefore help increase our understanding of variance in cognitive abilities in young animals, as well as over time. We followed 22 marmosets (11 male and 11 female) from infancy through to early adolescence. At 3 months old, the marmosets were trained to reliably touch a rewarded stimulus. At 5 months, behavior was observed within the natal group. At 9 months, the marmosets were given a visual discrimination task to assess learning ability. Mann-Whitney U tests found no sex or family size differences in number of errors at 3 or 9 months. While no significant relationships were found between behavior in the family and learning at 3 months, significant negative correlations were found between duration spent in locomotion and learning errors (p = .05), as well as between frequency of calm vocalizations and learning errors (p = .001) at 9 months. A U-shape curve was found between amount of social play and learning at 9 months. Positive family interactions, including moderate amounts of play, as well as calm individual behavior, may therefore be important in learning. This study sheds light on cognitive development in much younger marmosets than previously studied, and helps increase understanding of how individual differences in learning may arise.

Callitrichid responses to dead and dying infants: the effects of paternal bonding and cause of death.

Many primates show responses to dead infants, yet testing explanations for these behaviors has been difficult. Callitrichids present a unique opportunity to delineate between hypotheses, since unlike most species, male caretakers form closer social bonds with infants than mothers. Callitrichids are also known to commit infanticide, leaving obvious wounds that may enable them to more readily recognize death. We present: (1) a case study of a wild common marmoset (Callithrix jacchus) group responding to an infant's natural death, and (2) a review of published infant deaths across callitrichids (N = 16), testing for trends in the sex of reacting individuals and cause of death. In our case study, several group members frequently interacted with the dead infant, attempting to carry it. However, the strongest response was from a male that remained with the corpse for ~ 3 h, despite his group leaving the area. Across callitrichid species, corpse interactions were significantly sex-biased: 100% (N = 6) of accidental deaths involved corpse interaction by males (p = 0.007), compared to 60% (N = 3 of 5) by females (p = 0.095). Cause of death also played a significant role, with individuals attempting to carry dead infants in 100% (N = 6) of accidental deaths, but only 11.1% (N = 1 of 9) of infanticides (p = 0.001). Although the available literature is small and potentially subject to publication biases, these data support the idea that visually obvious wounds may influence callitrichids' perception of dead conspecifics. Additionally, male-biased patterns of corpse interaction in callitrichids indicate that social bonds likely shape reactions to the dead, in addition to kinship. While published data on primate thanatology are limited, this study demonstrates quantitative approaches that can provide empirical insights into primates' responses to dead conspecifics.

Close-range vocal interaction in the common marmoset (Callithrix jacchus).

Vocal communication in animals often involves taking turns vocalizing. In humans, turn-taking is a fundamental rule in conversation. Among non-human primates, the common marmoset is known to engage in antiphonal calling using phee calls and trill calls. Calls of the trill type are the most common, yet difficult to study, because they are not very loud and uttered in conditions when animals are in close proximity to one another. Here we recorded trill calls in captive pair-housed marmosets using wearable microphones, while the animals were together with their partner or separated, but within trill call range. Trills were exchanged mainly with the partner and not with other animals in the room. Animals placed outside the home cage increased their trill call rate and uttered more trills in response to their partner compared to strangers. The fundamental frequency, F0, of trills increased when animals were placed outside the cage. Our results indicate that trill calls can be monitored using wearable audio equipment and that minor changes in social context affect trill call interactions and spectral properties of trill calls.

Vasopressin, but not oxytocin, modulates responses to infant stimuli in marmosets providing care to dependent infants.

In family-living species, the quality and patterning of caregiving is the product of an individual's role within the family (mother, father, sibling) and parental experience, both of which interact with underlying neurobiological substrates. Among these substrates are the nonapeptides vasopressin and oxytocin, which modulate maternal, paternal, and alloparental care. We used a nonhuman primate model of the "nuclear family," the marmoset (Callithrix jacchus), to investigate relationships between caregiving experience, role within the family, and activation of either the oxytocin or vasopressin systems in shaping responsiveness to offspring. During two phases of offspring development (early infancy, juvenile), mothers, fathers, and older siblings were treated with vasopressin, oxytocin, or saline via intranasal application, and tested for responses to infant distress stimuli in a within-subjects design. Interest in infant stimuli was highest among marmosets that were caring for infants compared to those caring for juveniles, and parentally experienced marmosets were quicker to respond to infant stimuli than first-time caregivers. Moreover, marmosets treated with vasopressin showed enhanced responsiveness to infant stimuli compared to control stimuli only when caring for infants. Thus, in all classes of marmoset caregivers, vasopressin enhances responsiveness to infant-associated stimuli in caregivers during periods in which infant care is most crucial.

The Importance of Complementary Collaboration of Researchers, Veterinarians, and Husbandry Staff in the Successful Training of Marmoset Behavioral Assays.

Interest in marmosets as research models has seen exponential growth over the last decade, especially given that the research community is eager to improve on gaps with historical animal models for behavioral and cognitive disorders. The spectrum of human disease traits that present naturally in marmosets, as well as the range of analogous human behaviors that can be assessed in marmosets, makes them ideally suited as translational models for behavioral and cognitive disorders. Regardless of the specific research aims of any project, without close collaboration between researchers, veterinarians, and animal care staff, it would be impossible to meet these goals. Behavior is inherently variable, as are marmosets that are genetically and phenotypically diverse. Thus, to ensure rigor, reliability, and reproducibility in results, it is important that in the research environment, the animal's daily husbandry and veterinary needs are being met and align with the research goals while keeping the welfare of the animal the most critical and highest priority. Much of the information described herein provides details on key components for successful behavioral testing, based on a compendium of methods from peer-reviewed publications and our own experiences. Specific areas highlighted include habituation procedures, selection of appropriate rewards, optimization of testing environments, and ways to integrate regular veterinary and husbandry procedures into the research program with minimal disruptions to the behavioral testing plan. This article aims to provide a broad foundation for researchers new to establishing behavioral and cognitive testing paradigms in marmosets and especially for the veterinary and husbandry colleagues who are indispensable collaborators of these research projects.

Baseline cortisol levels and social behavior differ as a function of handedness in marmosets (Callithrix jacchus).

Population hand preferences are rare in nonhuman primates, but individual hand preferences are consistent over a lifetime and considered to reflect an individual's preference to use a particular hemisphere when engaged in a specific task. Previous findings in marmosets have indicated that left-handed individuals tend to be more fearful than their right-handed counterparts. Based on these findings, we tested the hypotheses that left-handed marmosets are (a) more reactive to a social stressor and (b) are slower than right-handed marmosets in acquiring a reversal learning task. We examined the hand preference of 27 male and female marmosets (ages of 4-7 years old) previously tested in a social separation task and a reversal learning task. Hand preference was determined via a simple reaching task. In the social separation task, monkeys were separated from their partner and the colony for a single 7-hr session. Urinary cortisol levels and behavior were assessed at baseline, during the separation and 24 hr postseparation. Hand preferences were equally distributed between left (n = 10), right-handed (n = 10), and ambidextrous (n = 7) individuals. The separation phase was associated with an increase in cortisol levels and behavioral changes that were similar across handedness groups. However, cortisol levels at baseline were positively correlated with right-handedness, and this relationship was stronger in females than in males. In addition, the occurrence of social behaviors (pre- and postseparation) was positively correlated with right-handedness in both sexes. Baseline cortisol levels did not correlate significantly with social behavior. Acquisition of the reversals was poorer in females than males but did not differ as a function of handedness. We conclude that (a) both stress reactivity and cognitive flexibility are similar across handedness groups and (b) left-handers exhibit less social behavior and have lower basal cortisol levels than ambidextrous and right-handed subjects. The underlying causes for these differences remain to be established.

Task-based fMRI of a free-viewing visuo-saccadic network in the marmoset monkey.

Saccadic tasks are often used to index aberrations of cognitive function in patient populations, with several neuropsychiatric and neurologic disorders characterized by saccadic dysfunction. The common marmoset (Callithrix jacchus) has received recent attention as an additional primate model for studying the neural basis of these dysfunctions - marmosets are amenable to a host of genetic manipulation techniques and have a lissencephalic cortex, which is well suited for a variety of recording techniques (e.g., calcium imaging, laminar electrophysiology). Because the marmoset cortex is mostly lissencephalic, however, the locations of frontal saccade-related regions (e.g., frontal eye fields (FEF)) are less readily identified than in Old World macaque monkeys. Further, although high quality histology-based atlases do exist for marmosets, identifying these regions based on histology alone is not always accurate, with the cytoarchitectonic boundaries often inconsonant with functional boundaries. As such, there is a need to map the functional location of these regions directly. Task-based functional magnetic resonance imaging (fMRI) is of utility in this regard, allowing for detection of whole-brain signal changes in response to moving stimuli. Here, we conducted task-based fMRI in marmosets at ultra-high field (9.4 T) during a free-viewing visuo-saccadic task. We also conducted the same task in humans at ultra-high field (7 T) to validate that our simple task was indeed evoking the visuo-saccadic circuitry we expected (as defined by a meta-analysis of fMRI saccade studies). In the marmosets, we found that the task evoked a robust visuo-saccadic topology, with visual cortex (V1, V2, V3, V4) activation extending ventrally to MT, MST, FST and dorsally into V6, 19M, 23V. This topology also included putative cingulate eye field (area 32 and 24d), posterior parietal cortex (with strongest activation in lateral intraparietal area (LIP)), and a frontolateral peak in area 8 aV in marmosets, extending into 45, 46, 8aD, 6DR, 8c, 6 aV, 6DC. Overall, these results support the view that marmosets are a promising preclinical modelling species for studying saccadic dysfunction related to neuropsychiatric or neurodegenerative human brain diseases.

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.

Personality and lateralization in common marmosets (Callithrix jacchus).

Specialization of the left and right hemispheres to control behavioural responses may represent one of the mechanisms underlying individual differences in personality structure, as well as the preferential use of one hand. The present study investigated the relationship between personality and hand preference in common marmosets (Callithrix jacchus), a little New World monkey that presents highly consistent and stable individual hand preferences for simple reaching. To address this issue, data on 56 different behaviours from the species' behavioural repertoire were measured in 10 different laboratory tests and during observations under social conditions on 16 adult common marmosets. Stable behavioural variables were aggregated a priori into 13 personality traits. Exploratory Factor Analysis (EFA) on personality traits was carried out to verify the presence of major personality factors, and their relationship with direction and strength of individual hand preferences was assessed by multiple regression, taking into account sex and age of the subjects. The largest number of species-specific behaviours so far investigated in this species was taken into account and robust temporal stability between two testing periods was verified. We confirm that common marmosets are characterized by specific and stable personality profiles. A single personality factor, accounting for about 38% of the total variance, was found by EFA, that describes the interest towards unusual and new experiences and resembles the human Openness domain. The strength of the hand preference was found to be predicted by this personality factor, that we named Inquisitiveness. Present results highlight common marmoset as a useful primate model for the study of the relationship between personality and lateralization.

Recognition Memory in Marmoset and Macaque Monkeys: A Comparison of Active Vision.

The core functional organization of the primate brain is remarkably conserved across the order, but behavioral differences evident between species likely reflect derived modifications in the underlying neural processes. Here, we performed the first study to directly compare visual recognition memory in two primate species-rhesus macaques and marmoset monkeys-on the same visual preferential looking task as a first step toward identifying similarities and differences in this cognitive process across the primate phylogeny. Preferences in looking behavior on the task were broadly similar between the species, with greater looking times for novel images compared with repeated images as well as a similarly strong preference for faces compared with other categories. Unexpectedly, we found large behavioral differences among the two species in looking behavior independent of image familiarity. Marmosets exhibited longer looking times, with greater variability compared with macaques, regardless of image content or familiarity. Perhaps most strikingly, marmosets shifted their gaze across the images more quickly, suggesting a different behavioral strategy when viewing images. Although such differences limit the comparison of recognition memory across these closely related species, they point to interesting differences in the mechanisms underlying active vision that have significant implications for future neurobiological investigations with these two nonhuman primate species. Elucidating whether these patterns are reflective of species or broader phylogenetic differences (e.g., between New World and Old World monkeys) necessitates a broader sample of primate taxa from across the Order.

One-year change in cognitive flexibility and fine motor function in middle-aged male and female marmosets (Callithrix jacchus).

The common marmoset (Callithrix jacchus) is uniquely suited for longitudinal studies of cognitive aging, due to a relatively short lifespan, sophisticated cognitive abilities, and patterns of brain aging that resemble those of humans. We examined cognitive function and fine motor skills in male and female marmosets (mean age ∼5 at study entry) followed longitudinally for 2 years. Each year, monkeys were tested on a reversal learning task with three pairs of stimuli (n = 18, 9 females) and a fine motor task requiring them to grasp small rewards from two staircases (Hill and Valley test, n = 12, 6 females). There was little evidence for a decline in cognitive flexibility between the two time points, in part because of practice effects. However, independent of year of testing, females took longer than males to reach criterion in the reversals, indicating impaired cognitive flexibility. Motivation was unlikely to contribute to this effect, as males refused a greater percentage of trials than females in the reversals. With regards to motor function, females were significantly faster than males in the Hill and Valley task. From Year 1 to Year 2, a slight slowing of motor function was observed in both sexes, but accuracy decreased significantly in males only. This study (1) demonstrates that marmosets exhibit sex differences in cognitive flexibility and fine motor function that resemble those described in humans; (2) that changes in fine motor function can already be detected at middle-age; and (3) that males may experience greater age-related changes in fine motor skills than females. Additional data points will determine whether these sex and age differences persist over time.