Age- and sex-related differences in baboon (Papio anubis) gray matter covariation.

Age-related changes in cognition, brain morphology, and behavior are exhibited in several primate species. Baboons, like humans, naturally develop Alzheimer's disease-like pathology and cognitive declines with age and are an underutilized model for studies of aging. To determine age-related differences in gray matter covariation of 89 olive baboons (Papio anubis), we used source-based morphometry (SBM) to analyze data from magnetic resonance images. We hypothesized that we would find significant age effects in one or more SBM components, particularly those which include regions influenced by age in humans and other nonhuman primates (NHPs). A multivariate analysis of variance revealed that individual weighted gray matter covariation scores differed across the age classes. Elderly baboons contributed significantly less to gray matter covariation components including the brainstem, superior parietal cortex, thalamus, and pallidum compared to juveniles, and middle and superior frontal cortex compared to juveniles and young adults (p < 0.05). Future studies should examine the relationship between the changes in gray matter covariation reported here and age-related cognitive decline.

Phenotypic and genetic associations between gray matter covariation and tool use skill in chimpanzees (Pan troglodytes): Repeatability in two genetically isolated populations.

Humans and chimpanzees both exhibit a diverse set of tool use skills which suggests selection for tool manufacture and use occurred in the common ancestors of the two species. Our group has previously reported phenotypic and genetic associations between tool use skill and gray matter covariation, as quantified by source-based morphometry (SBM), in chimpanzees. As a follow up study, here we evaluated repeatability in heritability in SBM components and their phenotypic association with tool use skill in two genetically independent chimpanzee cohorts. Within the two independent cohorts of chimpanzees, we identified 8 and 16 SBM components, respectively. Significant heritability was evident for multiple SBM components within both cohorts. Further, phenotypic associations between tool use performance and the SBM components were largely consistent between the two cohorts; the most consistent finding being an association between tool use performance and an SBM component including the posterior superior temporal sulcus (STS) and superior temporal gyrus (STG), and the interior and superior parietal regions (p < 0.05). These findings indicate that the STS, STG, and parietal cortices are phenotypically and genetically implicated in chimpanzee tool use abilities.

A neuroanatomical predictor of mirror self-recognition in chimpanzees.

The ability to recognize one's own reflection is shared by humans and only a few other species, including chimpanzees. However, this ability is highly variable across individual chimpanzees. In humans, self-recognition involves a distributed, right-lateralized network including frontal and parietal regions involved in the production and perception of action. The superior longitudinal fasciculus (SLF) is a system of white matter tracts linking these frontal and parietal regions. The current study measured mirror self-recognition (MSR) and SLF anatomy in 60 chimpanzees using diffusion tensor imaging. Successful self-recognition was associated with greater rightward asymmetry in the white matter of SLFII and SLFIII, and in SLFIII's gray matter terminations in Broca's area. We observed a visible progression of SLFIII's prefrontal extension in apes that show negative, ambiguous, and compelling evidence of MSR. Notably, SLFIII's terminations in Broca's area are not right-lateralized or particularly pronounced at the population level in chimpanzees, as they are in humans. Thus, chimpanzees with more human-like behavior show more human-like SLFIII connectivity. These results suggest that self-recognition may have co-emerged with adaptations to frontoparietal circuitry.

The influence of AVPR1A genotype on individual differences in behaviors during a mirror self-recognition task in chimpanzees (Pan troglodytes).

The mark/rouge test has been used to assess mirror self-recognition (MSR) in many species. Despite consistent evidence of MSR in great apes, genetic or non-genetic factors may account for the individual differences in behavioral responses that have been reported. We examined whether vasopressin receptor gene (AVPR1A) polymorphisms are associated with MSR-related behaviors in chimpanzees since vasopressin has been implicated in the development and evolution of complex social relations and cognition and chimpanzees are polymorphic for the presence of the RS3-containing DupB region. We compared a sample of DupB+/- and DupB-/- chimpanzees on a mark test to assess its role on social behavior toward a mirror. Chimpanzees were administered two, 10-min sessions where frequencies of mirror-guided self-directed behaviors, contingent actions and other social behaviors were recorded. Approximately one-third showed evidence of MSR and these individuals exhibited more mirror-guided self-exploratory behaviors and mouth contingent actions than chimpanzees not classified as passers. Moreover, DupB+/- males exhibited more scratching and agonistic behaviors than other male and female cohorts. Our findings support previous studies demonstrating individual differences in MSR abilities in chimpanzees and suggest that AVPR1A partly explains individual differences in MSR by influencing the behavioral reactions of chimpanzees in front of a mirror.

DUF1220 protein domains drive proliferation in human neural stem cells and are associated with increased cortical volume in anthropoid primates.

Genome sequences encoding DUF1220 protein domains show a burst in copy number among anthropoid species and especially humans, where they have undergone the greatest human lineage-specific copy number expansion of any protein coding sequence in the genome. While DUF1220 copy number shows a dosage-related association with brain size in both normal populations and in 1q21.1-associated microcephaly and macrocephaly, a function for these domains has not yet been described. Here we provide multiple lines of evidence supporting the view that DUF1220 domains function as drivers of neural stem cell proliferation among anthropoid species including humans. First, we show that brain MRI data from 131 individuals across 7 anthropoid species shows a strong correlation between DUF1220 copy number and multiple brain size-related measures. Using in situ hybridization analyses of human fetal brain, we also show that DUF1220 domains are expressed in the ventricular zone and primarily during human cortical neurogenesis, and are therefore expressed at the right time and place to be affecting cortical brain development. Finally, we demonstrate that in vitro expression of DUF1220 sequences in neural stem cells strongly promotes proliferation. Taken together, these data provide the strongest evidence so far reported implicating DUF1220 dosage in anthropoid and human brain expansion through mechanisms involving increasing neural stem cell proliferation.

Genetic and environmental contributions to the expression of handedness in chimpanzees (Pan troglodytes).

Most humans are right-handed and, like many behavioral traits, there is good evidence that genetic factors play a role in handedness. Many researchers have argued that non-human animal limb or hand preferences are not under genetic control but instead are determined by random, non-genetic factors. We used quantitative genetic analyses to estimate the genetic and environmental contributions to three measures of chimpanzee handedness. Results revealed significant population-level handedness for two of the three measures-the tube task and manual gestures. Furthermore, significant additive genetic effects for the direction and strength of handedness were found for all three measures, with some modulation due to early social rearing experiences. These findings challenge historical and contemporary views of the mechanisms underlying handedness in non-human animals.

Termite fishing laterality in the Fongoli savanna chimpanzees (Pan troglodytes verus): further evidence of a left hand preference.

Whether nonhuman primates show population-level handedness is a topic of much scientific debate. A previous study of handedness for termite fishing reported population-level left handedness in the chimpanzees from Gombe National Park, Tanzania. In the current study, we examined whether similar hand preferences were evident in a savanna-dwelling chimpanzee population with regards to termite fishing. Hand preference data were collected for 27 chimpanzees from February 2007 through July 2008 and November 2011 through January 2012 in southeastern Senegal. Overall, the Fongoli chimpanzees demonstrate a trend toward population-level handedness, though the results did not reach conventional levels of statistical significance likely due to the limited sample size. Fongoli chimpanzees showed the same pattern of left hand preference as reported at Gombe and the two populations did not differ significantly. When the data were combined across all studies, wild chimpanzees showed a population-level left hand preference for termite fishing.

A polymorphic indel containing the RS3 microsatellite in the 5' flanking region of the vasopressin V1a receptor gene is associated with chimpanzee (Pan troglodytes) personality.

Vasopressin is a neuropeptide that has been strongly implicated in the development and evolution of complex social relations and cognition in mammals. Recent studies in voles have shown that polymorphic variation in the promoter region of the arginine vasopressin V1a receptor gene (avpr1a) is associated with different dimensions of sociality. In humans, variation in a repetitive sequence element in the 5' flanking region of the AVPR1A, known as RS3, have also been associated with variation in AVPR1a gene expression, brain activity and social behavior. Here, we examined the association of polymorphic variation in this same 5' flanking region of the AVPR1A on subjective ratings of personality in a sample of 83 chimpanzees (Pan troglodytes). Initial analyses indicated that 34 females and 19 males were homozygous for the short allele, which lacks RS3 (DupB(-/-)), while 18 females and 12 males were heterozygous and thus had one copy of the long allele containing RS3 (DupB(+/-)), yielding overall allelic frequencies of 0.82 for the DupB(-) allele and 0.18 for the DupB(+) allele. DupB(+/+) chimpanzees were excluded from the analysis because of the limited number of individuals. Results indicated no significant sex difference in personality between chimpanzees homozygous for the deletion of the RS3-containing DupB region (DupB(-/-)); however, among chimpanzees carrying one allele with the DupB present (DupB(+/-)), males had significantly higher dominance and lower conscientiousness scores than females. These findings are the first evidence showing that the AVPR1A gene plays a role in different aspects of personality in male and female chimpanzees.

Observer-independent characterization of sulcal landmarks and depth asymmetry in the central sulcus of the chimpanzee brain.

The central sulcus (CS) divides primary motor and sensory cortex in many mammalian brains. Recent studies have shown that experiential factors can influence the volume and lateralization of the CS in both human and nonhuman primates. In this study, we sought to define specific landmarks and the depth of the CS region corresponding to the motor-hand area of chimpanzees for comparison with humans using a novel, observer independent method applied to sample of 32 magnetic resonance images (MRI) scans. Our results showed that the dorsal-ventral location of the motor-hand region is comparable between humans and chimpanzees, though the depth of the CS was significantly greater in humans compared to chimpanzees. We further found that CS area corresponding to the motor-hand area was significantly larger in the hemisphere contralateral to the chimpanzees preferred hand. The methods employed here offer some potential advantages over traditional region-of-interest in the comparative study of cortical organization and gyrification in primates and are discussed.

A comparative study of corpus callosum size and signal intensity in capuchin monkeys (Cebus apella) and chimpanzees (Pan troglodytes).

The evolution of corpus callosum (CC) was integral to the development of higher cognitive processes and hemispheric specialization. An examination of CC morphology and organization across different primate species will further our understanding of the evolution of these specified functions. Using magnetic resonance imaging (MRI) as a non-invasive technique to measure CC size and to approximate the degree of myelination in the corpus callosum, we report differences in CC morphology and organization in capuchin monkeys and chimpanzees, two divergent primate species that have independently evolved several behavioral and anatomical characteristics. Species differences in CC morphology were detected, with chimpanzees having a larger overall CC compared to capuchin monkeys. Additionally, chimpanzees had the genu as the largest subdivision; in capuchin monkeys, the genu and splenium were the largest subdivisions. Sex differences in signal intensity were detected; capuchin monkey males had higher signal intensity values whereas chimpanzee females had higher signal intensity values. Thus, while capuchin monkeys and chimpanzees show some similarity in patterns of CC morphology, these species differ significantly in the regional organization of the CC.

Handedness for tool use in captive chimpanzees (Pan troglodytes): Sex differences, performance, heritability and comparison to the wild.

There is continued debate over the factors influencing handedness in captive and wild primates, notably chimpanzees. Previous studies in wild chimpanzees have revealed population-level left handedness for termite fishing. Here we examined hand preferences and performance on a tool use task designed to simulate termite fishing in a sample of 190 captive chimpanzees to evaluate whether patterns of hand use in captive chimpanzees differed from those observed for wild apes. No population-level handedness was found for this task; however, significant sex differences in preference and performance were found, with males showing greater left handedness and poorer performance compared to females. We also found that the hand preferences of offspring were significantly positively correlated with the hand preferences of their mothers. Lastly, older females performed more slowly on the task compared to younger individuals. The overall results neither confirm nor reject previous hypotheses claiming that raising chimpanzees in captivity induces right-handedness, but rather suggest that other factors may account for differences in hand preferences for tool use seen in wild and captive chimpanzees.

Asymmetric Broca's area in great apes.

Brodmann's area 44 delineates part of Broca's area within the inferior frontal gyrus of the human brain and is a critical region for speech production, being larger in the left hemisphere than in the right - an asymmetry that has been correlated with language dominance. Here we show that there is a similar asymmetry in this area, also with left-hemisphere dominance, in three great ape species (Pan troglodytes, Pan paniscus and Gorilla gorilla). Our findings suggest that the neuroanatomical substrates for left-hemisphere dominance in speech production were evident at least five million years ago and are not unique to hominid evolution.

Neuroanatomical localization of the motor hand area with magnetic resonance imaging: the left hemisphere is larger in great apes.

Magnetic resonance images of the brain were obtained from 2 gorillas (Gorilla gorilla gorilla), 4 orangutans (Pongo pygmaeus), 14 chimpanzees (Pan troglodytes), and 4 bonobos (Pan paniscus). The region on the motor cortex of humans identified as responsible for motor skill of the hand (the "knob") was identified in this sample on consecutive 1-mm axial scans. The shape of the knob area was traced on each scan from both hemispheres, and the area from all scans was summed to calculate the knob volume. The width of the knob was also measured and correlated highly with knob volume. A significant population-level leftward asymmetry in the volume and width of the knob was revealed (p < .05). Species differences in knob asymmetry and overall volume were not significant, but the variability in overall volume between species was substantial. Selection for the evolution of a neuroanatomical representation of the hand in primates and an evolutionary trend toward population-level right handedness are discussed.

The use of bouts and frequencies in the evaluation of hand preferences for a coordinated bimanual task in chimpanzees (Pan troglodytes): an empirical study comparing two different indices of laterality.

Hand preferences for a coordinated bimanual task were assessed in 109 chimpanzees (Pan troglodytes). Hand preference was evaluated for 4 test sessions using bouts and frequencies of hand use to compare the sensitivity of each level of analysis in evaluating individual variation in handedness. Overall, significant population-level right-handedness was found using several different measures of hand use. Handedness indices based on bouts and frequencies were highly and significantly correlated. Moreover, hand preferences were consistent across tests despite efforts to situationally bias preference during each test. Taken together, these data do not support the view that bouts are a better level of analysis for evaluating hand preference. The results further suggest that hand preferences for coordinated bimanual actions are not influenced by situational factors and may reflect an inherent specialization of the left hemisphere for motor skill.

Effects of cognitive challenge on self-directed behaviors by chimpanzees (Pan troglodytes).

In primates, including humans, scratching and other self-directed behaviors (SDBs) have recently been reported to be differentially displayed as a function of social interactions, anxiety-related drugs, and response outcomes during learning tasks. Yet few studies have focused on the factors influencing SDBs in our closest living relatives, the chimpanzees (Pan troglodytes). Furthermore, no previous experimental study has examined handedness of SDBs as a function of changes in task difficulty. Using matching-to-sample tasks of varying difficulty, the present study examines the effect of manipulations of task difficulty on rates, handedness, and type of SDBs in an experimental study of eight chimpanzees. SDBs were categorized as rubs, gentle scratches, and rough scratches. SDBs increased during difficult discriminations, but only for subjects who started the experiment on an easy discrimination; subjects who started on a difficult discrimination exhibited no differential rates of SDBs as a function of task difficulty. There was a tendency to exhibit relatively more SDBs with the right hand in the more difficult task. Rates of SDBs decreased after auditory feedback signals, suggesting a link between SDBs and uncertainty. Rubs were directed more to the face (trigeminal), and gentle and rough scratches more to the body (spinothalamic), suggesting that face-directed SDBs may index a different motivational basis than scratches. Taken together, these results extend previous research on SDBs to the domain of cognitive stress in nonsocial contexts, demonstrating that SDBs are sensitive to manipulations of task difficulty in chimpanzees.

Genetic influence on the expression of hand preferences in chimpanzees (Pan troglodytes): evidence in support of the right-shift theory and developmental instability.

Genetic mechanisms have been proposed to explain the pervasive representation of right-handedness in humans, whereas random, nongenetic factors have been posited to explain the lack of population-level right-handedness in nonhuman primates. We report evidence that hand preferences in chimpanzees are heritable, even among related individuals raised in different environments. Furthermore, we report that the degree of heritability is modified by factors associated with developmental instability, notably, offspring parity. The data are interpreted to reconcile both genetic models for handedness and hypotheses suggesting that developmental instability influences variation in handedness.

Cerebral volumetric asymmetries in non-human primates: a magnetic resonance imaging study.

Magnetic resonance images (MRI) were collected in a sample of 23 apes, 14 Old World monkeys, and 8 New World monkeys. The total area or volume of the anterior and posterior cerebral regions of each hemisphere of the brain was measured. The results indicated that a rightward frontal and leftward occipital pattern of asymmetry was present at a population level in the great ape sample. Population-level cerebral asymmetries were not revealed in the sample of New or Old World monkeys. The total area or volume of the planum temporale, which was localised only in the great apes, was also measured in both hemispheres. A leftward planum temporale asymmetry was evident at the population level in the great apes. It was hypothesised that the rightward frontal and leftward occipital asymmetries would correlate with leftward planum temporale asymmetries. This hypothesis was based on the assumption that, similar to development of the human brain, the nonhuman primate brain ''torques'' during development due to a growth gradient which progresses anterior to posterior, ventral to dorsal, and right to left. The results of this study confirmed the predicted relationship between cerebral volume and the planum temporale asymmetries. This supports the hypothesis that the great ape brain may develop in a ''torquing'' manner, producing similar anatomical asymmetries as reported in humans.

Differential use of vocal and gestural communication by chimpanzees (Pan troglodytes) in response to the attentional status of a human (Homo sapiens).

This study examined the communicative behavior of 49 captive chimpanzees (Pan troglodytes), particularly their use of vocalizations, manual gestures, and other auditory- or tactile-based behaviors as a means of gaining an inattentive audience's attention. A human (Homo sapiens) experimenter held a banana while oriented either toward or away from the chimpanzee. The chimpanzees' behavior was recorded for 60 s. Chimpanzees emitted vocalizations faster and were more likely to produce vocalizations as their 1st communicative behavior when a human was oriented away from them. Chimpanzees used manual gestures more frequently and faster when the human was oriented toward them. These results replicate the findings of earlier studies on chimpanzee gestural communication and provide new information about the intentional and functional use of their vocalizations.

Birth order and left-handedness revisited: some recent findings in chimpanzees (Pan troglodytes) and their implications for developmental and evolutionary models of human handedness.

This paper examines the relationship between parity, pregnancy outcome, and handedness in a sample of captive chimpanzees (Pan troglodytes). The relation between parity, maternal age and positive or negative pregnancy outcome was assessed from life history data for 536 chimpanzees housed at the Yerkes Regional Primate Research Center. The incidences of negative pregnancy outcome (notably spontaneous abortions and stillbirths) were significantly higher in parities of 8 or higher compared to all other parities. In a sub-sample of 165 chimpanzees, the relation between parity, maternal age and handedness was assessed to determine whether left handedness may serve as a marker of prenatal pathology. These analyses indicated that left-handedness was more prevalent in 1st and 8 or higher parities compared to parities between 2 and 7, respectively. Possible prenatal hormonal and periparturitional factors are discussed as possible mechanisms for the observed findings.