Neutrophil to lymphocyte ratio in captive olive baboons (Papio anubis): The effects of age, sex, rearing, stress, and pregnancy.

In apes and humans, neutrophil to lymphocyte ratio (NLR) can be used as a predictive indicator of a variety of clinical conditions, longevity, and physiological stress. In chimpanzees specifically, NLR systematically varies with age, rearing, sex, and premature death, indicating that NLR may be a useful diagnostic tool in assessing primate health. To date, just one very recent study has investigated NLR in old world monkeys and found lower NLR in males and nursery-reared individuals, as well as a negative relationship between NLR and disease outcomes. Given that baboons are increasingly used as research models, we aimed to characterize NLR in baboons by providing descriptive data and examinations of baboon NLR heritability, and of the relationships between NLR, age, rearing, and sex in 387 olive baboons (Papio anubis) between 6 months and 19 years of age. We found that (1) mother-reared baboons had higher NLRs than nursery-reared baboons; (2) females had higher NLRs than males; and (3) there was a quadratic relationship between NLR and age, such that middle-aged individuals had the highest NLR values. We also examined NLR as a function of transport to a new facility using a subset of the data. Baboons exhibited significantly higher transport NLRs compared to routine exam NLRs. More specifically, adult baboons had higher transport NLRs than routine NLRs, whereas juveniles showed no such difference, suggesting that younger animals may experience transport stress differently than older animals. We also found that transport NLR was heritable, whereas routine NLR was not, possibly suggesting that stress responses (as indicated in NLR) have a strong genetic component. Consistent with research in humans and chimpanzees, these findings suggest that NLR varies with important biological and life history variables and that NLR may be a useful health biomarker in baboons.

The Effects of Oral Lavender Therapy on Wounding in Chimpanzees (Pan troglodytes).

Lavender administration in humans has been shown to promote calmness without the side effects often observed with benzodiazepines. Studies in both humans and rodents have found that ingestion of oral lavender capsules resulted in significantly decreased anxiety. Additionally, mice developed an anti-conflict effect and humans increased socially inclusive behaviors. Given the safety of oral lavender oil and the observed benefits, we administered daily lavender capsules to six chimpanzees who exhibited conflict-instigating behaviors in an effort to further decrease our already low levels of wounding. We compared the total number of wounds in 25 chimpanzees housed with the six lavender-treated chimpanzees in five different social groups (1) prior to administration of daily oral lavender capsules to (2) total wounds during daily oral lavender capsule treatment. We hypothesized that lavender therapy treatment would reduce overall wounding in the social groups. Surprisingly, overall wounding was higher during the lavender treatment period (p = 0.01), yet the percentage of wounds requiring treatment significantly decreased during the lavender therapy period (36% vs. 21%, p = 0.02).

Age differences in cortical thickness and their association with cognition in chimpanzee (Pan troglodytes).

Humans and chimpanzees are genetically similar and share a number of life history, behavioral, cognitive and neuroanatomical similarities. Notwithstanding, our understanding of age-related changes in cognitive and motor functions in chimpanzees remains largely unstudied despite recent evident demonstrating that chimpanzees exhibit many of the same neuropathological features of Alzheimer's disease observed in human postmortem brains. Here, we examined age-related differences in cognition and cortical thickness measured from magnetic resonance images in a sample of 215 chimpanzees ranging in age between 9 and 54 years. We found that chimpanzees showed global and region-specific thinning of cortex with increasing age. Further, within the elderly cohort, chimpanzees that performed better than average had thicker cortex in frontal, temporal and parietal regions compared to chimpanzees that performed worse than average. Independent of age, we also found sex differences in cortical thickness in 4 brain regions. Males had higher adjusted cortical thickness scores for the caudal anterior cingulate, rostral anterior cingulate, and medial orbital frontal while females had higher values for the inferior parietal cortex. We found no evidence that increasing age nor sex was associated with asymmetries in cortical thickness. Moreover, age-related differences in cognitive function were only weakly associated with asymmetries in cortical thickness. In summary, as has been reported in humans and other primates, elderly chimpanzees show thinner cortex and variation in cortical thickness is associated with general cognitive functions.

Genetic determinants of individual variation in the superior temporal sulcus of chimpanzees (Pan troglodytes).

The superior temporal sulcus (STS) is a conserved fold that divides the middle and superior temporal gyri. In humans, there is considerable variation in the shape, folding pattern, lateralization, and depth of the STS that have been reported to be associated with social cognition and linguistic functions. We examined the role that genetic factors play on individual variation in STS morphology in chimpanzees. The surface area and depth of the STS were quantified in sample of 292 captive chimpanzees comprised of two genetically isolated population of individuals. The chimpanzees had been previously genotyped for AVPR1A and KIAA0319, two genes that play a role in social cognition and communication in humans. Single nucleotide polymorphisms in the KIAA0319 and AVPR1A genes were associated with average depth as well as asymmetries in the STS. By contrast, we found no significant effects of these KIA0319 and AVPR1A polymorphism on surface area and depth measures for the central sulcus. The overall findings indicate that genetic factors account for a small to moderate amount of variation in STS morphology in chimpanzees. These findings are discussed in the context of the role of the STS in social cognition and language in humans and their potential evolutionary origins.

Neuroanatomical correlates of individual differences in the object choice task in chimpanzees (Pan troglodytes).

Declarative and imperative joint attention or joint engagement are important milestones in human infant development. These have been shown to be a significant predictor of later language development and are impaired in some individuals with, or at risk for, a diagnosis of autism spectrum disorder. Comparatively, while chimpanzees and other great apes have been reported to engage in imperative joint attention, evidence of declarative joint attention remains unclear based on existing studies. Some have suggested that differences in methods of assessing joint attention may have an influence on performance in nonhuman primates. Here, we report data on a measure of receptive joint attention (object choice task) in a sample of captive chimpanzees. Chimpanzees, as a group, performed significantly better than chance. By contrast, when considering individual performance, there was no significant difference in the number of those who passed and those who failed. Using quantitative genetic analyses, we found that performance on the object choice task was not significantly heritable nor were there any significant effects of sex, rearing history, or colony. Lastly, we found significant differences in gray matter covariation, between those who passed or failed the task. Those who passed contributed more to gray matter covariation in several brain regions within the social brain network, consistent with hypotheses regarding the importance of these regions in human and nonhuman primate social cognition.

The Role of Serotonergic Gene Methylation in Regulating Anxiety-Related Personality Traits in Chimpanzees.

While low serotonergic activity is often associated with psychological disorders such as depression, anxiety, mood, and personality disorders, variations in serotonin also contribute to normal personality differences. In this study, we investigated the role of blood DNA methylation levels at individual CpG sites of two key serotonergic genes (serotonin receptor gene 1A, HTR1A; serotonin transporter gene, SLC6A4) in predicting the personalities of captive chimpanzees. We found associations between methylation at 9/48 CpG sites with four personality dimensions: Dominance, Reactivity/Dependability, Agreeableness, and Openness. Directionality of effects were CpG location-dependent and confirmed a role of serotonergic methylation in reducing anxiety (Dominance) and aggression-related personality (Reactivity/Undependability) while simultaneously promoting prosocial (Agreeableness) and exploratory personalities (Openness). Although early-life adversity has been shown to impact serotonergic methylation patterns in other species, here, atypical early social rearing experiences only had a modest impact on CpG methylation levels in this chimpanzee sample. The precise environmental factors impacting serotonergic methylation in chimpanzees remain to be identified. Nevertheless, our study suggests a role in shaping natural variation in animal personalities. The results of this study offer a basis for future hypothesis-driven testing in additional populations and species to better understand the impact of ecology and evolution on complex behavioral traits.

Innovative multi-material tool use in the pant-hoot display of a chimpanzee.

'Pant-hoot displays' are a species-typical, multi-modal communicative behaviour in chimpanzees in which pant-hoot vocalisations are combined with varied behavioural displays. In both captivity and the wild, individuals commonly incorporate striking or throwing elements of their environment into these displays. In this case study, we present five videos of an unenculturated, captive, adult male chimpanzee combining a large rubber feeding tub with excelsior (wood wool) in a multi-step process, which was then integrated into the subject's pant-hoot displays as a percussive tool or 'instrument'. During the construction process, the subject demonstrated an understanding of the relevant properties of these materials, 'repairing' the tub to be a more functional drum when necessary. We supplement these videos with a survey of care staff from the study site for additional detail and context. Although care must be taken in generalising data from a single individual, the behaviour reported here hints at three intriguing features of chimpanzee communicative cognition: (1) it suggests a degree of voluntary control over vocal production, (2) it is a so-far unique example of compound tool innovation and use in communicative behaviour and (3) it may represent an example of forward planning in communicative behaviour. Each of these would represent hitherto undocumented dimensions of flexibility in chimpanzee communication, mapping fertile ground for future research.

A songbird can detect the eyes of conspecifics under daylight and artificial nighttime lighting.

Eyes convey important information about the external and internal worlds of animals. Individuals can follow the gaze of others to learn about the location of salient objects as well as assess eye qualities to evaluate the health, age or other internal states of conspecifics. Because of the increasing prevalence of artificial lighting at night (ALAN), urbanized individuals can potentially garner information from conspecific eyes under both daylight and ALAN. We tested this possibility using a visual modeling approach in which we estimated the maximum distance at which individuals could detect conspecific eyes under daylight and high levels of ALAN. We also estimated the minimum light level at which individuals could detect conspecific eyes. Great-tailed grackles (Quiscalus mexicanus) were used as our study species because they are highly social and are unusual among birds in that they regularly gather at nocturnal roosts in areas with high levels of ALAN. This visual modelling approach revealed that grackles can detect conspecific eyes under both daylight and ALAN, regardless of iris coloration. The grackles could detect conspecific eyes at farther distances in daylight compared to ALAN. Our results highlight the potential importance of lighting conditions in shaping social interactions.

The gaze of a social monkey is perceptible to conspecifics and predators but not prey.

Eye gaze is an important source of information for animals, implicated in communication, cooperation, hunting and antipredator behaviour. Gaze perception and its cognitive underpinnings are much studied in primates, but the specific features that are used to estimate gaze can be difficult to isolate behaviourally. We photographed 13 laboratory-housed tufted capuchin monkeys (Sapajus [Cebus] apella) to quantify chromatic and achromatic contrasts between their iris, pupil, sclera and skin. We used colour vision models to quantify the degree to which capuchin eye gaze is discriminable to capuchins, their predators and their prey. We found that capuchins, regardless of their colour vision phenotype, as well as their predators, were capable of effectively discriminating capuchin gaze across ecologically relevant distances. Their prey, in contrast, were not capable of discriminating capuchin gaze, even under relatively ideal conditions. These results suggest that specific features of primate eyes can influence gaze perception, both within and across species.

Chimpanzee (Pan troglodytes) gaze is conspicuous at ecologically-relevant distances.

Chimpanzee (Pan troglodytes) sclera appear much darker than the white sclera of human eyes, to such a degree that the direction of chimpanzee gaze may be concealed from conspecifics. Recent debate surrounding this topic has produced mixed results, with some evidence suggesting that (1) primate gaze is indeed concealed from their conspecifics, and (2) gaze colouration is among the suite of traits that distinguish uniquely social and cooperative humans from other primates (the cooperative eye hypothesis). Using a visual modelling approach that properly accounts for specific-specific vision, we reexamined this topic to estimate the extent to which chimpanzee eye coloration is discriminable. We photographed the faces of captive chimpanzees and quantified the discriminability of their pupil, iris, sclera, and surrounding skin. We considered biases of cameras, lighting conditions, and commercial photography software along with primate visual acuity, colour sensitivity, and discrimination ability. Our visual modeling of chimpanzee eye coloration suggests that chimpanzee gaze is visible to conspecifics at a range of distances (within approximately 10 m) appropriate for many species-typical behaviours. We also found that chimpanzee gaze is discriminable to the visual system of primates that chimpanzees prey upon, Colobus monkeys. Chimpanzee sclera colour does not effectively conceal gaze, and we discuss this result with regard to the cooperative eye hypothesis, the evolution of primate eye colouration, and methodological best practices for future primate visual ecology research.

Chimpanzee Extraversion scores vary with epigenetic modification of dopamine receptor gene D2 (DRD2) and early rearing conditions.

Chimpanzees have consistent individual differences in behaviour, also referred to as personality. Similar to human personality structure, five dimensions are commonly found in chimpanzee studies that show evidence for convergent and predictive validity (Dominance, Openness, Extraversion, Agreeableness, and Reactivity/Undependability). These dimensions are to some extent heritable, indicating a genetic component that explains part of the variation in personality scores, but are also influenced by environmental factors, such as the early social rearing background of the individuals. In this study, we investigated the role of epigenetic modification of the dopamine receptor D2 gene (DRD2) as a potential mechanism underlying personality variation in 51 captive chimpanzees. We used previously collected personality trait rating data and determined levels of DRD2 CpG methylation in peripheral blood samples for these same individuals. Results showed that DRD2 methylation is most strongly associated with Extraversion, and that varying methylation levels at specific DRD2 sites are associated with changes in Extraversion in nursery-reared, but not mother-reared, individuals. These results highlight the role of dopaminergic signalling in chimpanzee personality, and indicate that environmental factors, such as social experiences early in life, can have long-lasting behavioural effects, potentially through modification of the epigenome. These findings add to the growing evidence demonstrating the importance of the experience-dependent methylome for the development of complex social traits like personality.

Gray Matter Variation in the Posterior Superior Temporal Gyrus Is Associated with Polymorphisms in the KIAA0319 Gene in Chimpanzees (Pan troglodytes).

Determining the impact that the KIAA0319 gene has on primate brain morphology can provide insight into the evolution of human cognition and language systems. Here, we tested whether polymorphisms in KIAA0319 in chimpanzees account for gray matter volumetric variation in brain regions implicated in language and communication (particularly within the posterior superior temporal gyrus and inferior frontal gyrus). First, we identified the nature and frequencies of single nucleotide variants (SNVs) in KIAA0319 in a sample of unrelated chimpanzees (Pan troglodytes spp.). Next, we genotyped a subset of SNVs (those important for gene regulation or likely to alter protein structure/function) in a sample of chimpanzees for which in vivo T1-structural magnetic resonance imaging scans had been obtained. We then used source-based morphometry (SBM) to test for whole-brain gray matter covariation differences between chimpanzees with different KIAA0319 alleles. Finally, using histologic sections of 15 postmortem chimpanzee brains, we analyzed microstructural variation related to KIAA0319 polymorphisms in the posterior superior temporal cortex. We found that the SNVs were associated with variation in gray matter within several brain regions, including the posterior superior temporal gyrus (a region associated with language comprehension and production in humans). The microstructure analysis further revealed hemispheric differences in neuropil fraction, indicating that KIAA0319 expression may be involved in regulation of processes related to the formation and maintenance of synapses, dendrites, or axons within regions associated with communication.

Are conspecific social videos rewarding to chimpanzees (Pan troglodytes)? A test of the social motivation theory.

Many claim that social stimuli are rewarding to primates, but few, if any, studies have explicitly demonstrated their reward value. Here, we examined whether chimpanzees would produce overt responses for the opportunity to view conspecific social, compared to dynamic (video: Experiment 1) and static (picture: Experiment 2) control content. We also explored the relationships between variation in social reward and social behavior and cognition. We provided captive chimpanzees with access to a touchscreen during four, one-hour sessions (two 'conspecific social' and two 'control'). The sessions consisted of ten, 15-second videos (or pictures in Experiment 2) of either chimpanzees engaging in a variety of behaviors (social condition) or vehicles, humans, or other animals engaged in some activity (control condition). For each chimpanzee, we recorded the number of responses to the touchscreen and the frequency of watching the stimuli. Independent t-tests revealed no sex or rearing differences in touching and watching the social or control videos (p>0.05). Repeated measures ANOVAs showed chimpanzees touched and watched the screen significantly more often during the social compared to control video sessions. Furthermore, although chimpanzees did not touch the screen more often during social than control picture sessions in Experiment 2, they did watch the screen more often. Additionally, chimpanzees that previously performed better on a task of social cognition and engaged in more affiliative behavior watched a higher percentage of social videos during the touchscreen task. These results are consistent with the social motivation theory, and indicate social stimuli are intrinsically rewarding, as chimpanzees made more overt responses for the opportunity to view conspecific social, compared to control, content.

Age-related cognitive impairment is associated with low serum concentrations of testosterone and CSF levels of amyloid beta 42 in male cynomolgus monkeys (Macaca fascicularis).

Aged memory-impaired cynomolgus monkeys had significantly lower levels of cerebrospinal amyloid (Aß42 ) and serum testosterone compared with young animals and non-memory-impaired controls. Our findings confirm similar findings in the human and substantiate the usefulness of the cynomolgus monkey as a spontaneous model for aging-associated senile dementia of the Alzheimer type.

Playbacks of food-associated calls attract chimpanzees towards known food patches in a captive setting.

Food-associated calls have received much research attention due to their potential to refer to discovered food in a word-like manner. Studies have found that in many species, food-associated calls attract receivers to the food patch, suggesting these calls play roles in food sharing, cooperation and competition. Additionally, in various species, these calls play a role that has received much less attention: mediating social interactions among foragers that are already nearby or within the food patch, independently of whether they attract outside foragers. In order to increase understanding of the function of the chimpanzee (Pan troglodytes) food-associated rough grunt, we conducted captive playback studies testing whether rough grunt playbacks attract, repel or have no effect on the proximity of foragers already familiarized with the presence of food. We tested how acoustic playbacks of rough grunts (or control calls) from one of two known, identical feeding sites affected receivers' approach and feeding behaviors. More often than expected, participants first approached the feeding site from which rough grunts, but not control calls, were broadcast. However, neither condition increased the likelihood that participants fed first from a given site. Our results support the hypothesis that rough grunts elicit an approach response in receivers, while providing no evidence that they repel. In addition, our study provides evidence that receivers may approach rough grunts even if they do not intend to feed. We discuss the information rough grunts may convey to receivers beyond information about discovered food and the potential benefits signalers may gain from this calling behavior.

Increased expression of GAPDH in cynomolgus monkeys with spontaneous cognitive decline and amyloidopathy reminiscent of an Alzheimer's-type disease is reflected in the circulation.

Previous studies of aging cynomolgus monkeys from our group identified spontaneous age-associated cognitive declines associated with biomarkers and brain lesions reminiscent of Alzheimer's Disease (AD), in a proportion of aged monkeys. However, the molecular mechanisms that underlie the spontaneous amyloid disorders and cognitive declines observed in these affected monkeys have yet to be investigated in detail. Using reverse transcriptase quantitative real time PCR techniques, normalized to the ACTB housekeeping gene, we analyzed the expression patterns of a number of genes which have been implicated in amyloid and tau abnormalities, in well-characterized aged cynomolgus monkeys with cognitive decline. A significantly increased expression of the genes coding for glyceraldehyde 3-phosphate dehydrogenase (GAPDH), was found in aged-cognitive decline monkeys compared to age-matched healthy controls. GAPDH has been implicated in several neurodegenerative diseases and interacts with beta amyloid precursor proteins. These findings provide support for the utilization of cynomolgus macaques in translational preclinical research as valid spontaneous models in experimental investigations of the relationships among aging, cognitive decline, and the neuropathy of AD.

Reply to comment on "Nonadjacent dependency processing in monkeys, apes, and humans".

Rawski et al. revisit our recent findings suggesting the latent ability to process nonadjacent dependencies ("Non-ADs") in monkeys and apes. Specifically, the authors question the relevance of our findings for the evolution of human syntax. We argue that (i) these conclusions hinge upon an assumption that language processing is necessarily hierarchical, which remains an open question, and (ii) our goal was to probe the foundational cognitive mechanisms facilitating the processing of syntactic Non-ADs-namely, the ability to recognize predictive relationships in the input.

Predicting their past: Machine language learning can discriminate the brains of chimpanzees with different early-life social rearing experiences.

Early life experiences, including separation from caregivers, can result in substantial, persistent effects on neural, behavioral, and physiological systems as is evidenced in a long-standing literature and consistent findings across species, populations, and experimental models. In humans and other animals, differential rearing conditions can affect brain structure and function. We tested for whole brain patterns of morphological difference between 108 chimpanzees reared typically with their mothers (MR; N = 54) and those reared decades ago in a nursery with peers, human caregivers, and environmental enrichment (NR; N = 54). We applied support vector machine (SVM) learning to archival MRI images of chimpanzee brains to test whether we could, with any degree of significant probability, retrospectively classify subjects as MR and NR based on variation in gray matter within the entire brain. We could accurately discriminate MR and NR chimpanzee brains with nearly 70% accuracy. The combined brain regions discriminating the two rearing groups were widespread throughout the cortex. We believe this is the first report using machine language learning as an analytic method for discriminating nonhuman primate brains based on early rearing experiences. In this sense, the approach and findings are novel, and we hope they stimulate application of the technique to studies on neural outcomes associated with early experiences. The findings underscore the potential for infant separation from caregivers to leave a long-term mark on the developing brain.

Age- and cognition-related differences in the gray matter volume of the chimpanzee brain (Pan troglodytes): A voxel-based morphometry and conjunction analysis.

Several primate species have been shown to exhibit age-related changes in cognition, brain, and behavior. However, severe neurodegenerative illnesses, such as Alzheimer's disease (AD), were once thought to be uniquely human. Recently, some chimpanzees naturally were documented to develop both neurofibrillary tangles and amyloid plaques, the main characteristics of AD pathology. In addition, like humans and other primates, chimpanzees show similar declines in cognition and motor function with age. Here, we used voxel-based morphometry to examine the relationships among gray matter volume, age, and cognition using magnetic resonance imaging scans previously acquired from chimpanzees (N = 216). We first determined the relationship between age and gray matter volume, identifying the regions that declined with age. With a subset of our sample (N = 103), we also determined differences in gray matter volume between older chimpanzees with higher cognition scores than expected for their age, and older chimpanzees with lower than expected scores. Finally, we ran a conjunction analysis to determine any overlap in brain regions between these two analyses. We found that as chimpanzees age, they lose gray matter in regions associated with cognition. In addition, cognitively healthy older chimpanzees (those performing better for their age) have greater gray matter volume in many brain regions compared with chimpanzees who underperform for their age. Finally, the conjunction analysis revealed that regions of age-related decline overlap with the regions that differ between cognitively healthy chimpanzees and those who underperform. This study provides further evidence that chimpanzees are an important model for research on the neurobiology of aging. Future studies should investigate the effects of cognitive stimulation on both cognitive performance and brain structure in aging nonhuman primates.

Sulcal Morphology in Cingulate Cortex is Associated with Voluntary Oro-Facial Motor Control and Gestural Communication in Chimpanzees (Pan troglodytes).

Individual differences in sulcal variation within the anterior and mid-cingulate cortex of the human brain, particularly the presence or absence of a paracingulate sulcus (PCGS), are associated with various motor and cognitive processes. Recently, it has been reported that chimpanzees possess a PCGS, previously thought to be a unique feature of the human brain. Here, we examined whether individual variation in the presence or absence of a PCGS as well as the variability in the intralimbic sulcus (ILS) are associated with oro-facial motor control, handedness for manual gestures, and sex in a sample of MRI scans obtained in 225 chimpanzees. Additionally, we quantified the depth of the cingulate sulcus (CGS) along the anterior-posterior axis and tested for association with oro-facial motor control, handedness, and sex. Chimpanzees with better oro-facial motor control were more likely to have a PCGS, particularly in the left hemisphere compared to those with poorer control. Male chimpanzees with better oro-facial motor control showed increased leftward asymmetries in the depth of the anterior CGS, whereas female chimpanzees showed the opposite pattern. Significantly, more chimpanzees had an ILS in the left compared to the right hemisphere, but variability in this fold was not associated with sex, handedness, or oro-facial motor control. Finally, significant population-level leftward asymmetries were found in the anterior portion of the CGS, whereas significant rightward biases were evident in the posterior regions. The collective results suggest that the emergence of a PCGS and enhanced gyrification within the anterior and mid-cingulate gyrus may have directly or indirectly evolved in response to selection for increasing oro-facial motor control in primates.