Evolutionarily conserved neural responses to affective touch in monkeys transcend consciousness and change with age.

Affective touch-a slow, gentle, and pleasant form of touch-activates a different neural network than which is activated during discriminative touch in humans. Affective touch perception is enabled by specialized low-threshold mechanoreceptors in the skin with unmyelinated fibers called C tactile (CT) afferents. These CT afferents are conserved across mammalian species, including macaque monkeys. However, it is unknown whether the neural representation of affective touch is the same across species and whether affective touch's capacity to activate the hubs of the brain that compute socioaffective information requires conscious perception. Here, we used functional MRI to assess the preferential activation of neural hubs by slow (affective) vs. fast (discriminative) touch in anesthetized rhesus monkeys (Macaca mulatta). The insula, anterior cingulate cortex (ACC), amygdala, and secondary somatosensory cortex were all significantly more active during slow touch relative to fast touch, suggesting homologous activation of the interoceptive-allostatic network across primate species during affective touch. Further, we found that neural responses to affective vs. discriminative touch in the insula and ACC (the primary cortical hubs for interoceptive processing) changed significantly with age. Insula and ACC in younger animals differentiated between slow and fast touch, while activity was comparable between conditions for aged monkeys (equivalent to >70 y in humans). These results, together with prior studies establishing conserved peripheral nervous system mechanisms of affective touch transduction, suggest that neural responses to affective touch are evolutionarily conserved in monkeys, significantly impacted in old age, and do not necessitate conscious experience of touch.

See no evil: Attentional bias toward threat is diminished in aged monkeys.

Prior evidence demonstrates that relative to younger adults, older human adults exhibit attentional biases toward positive and/or away from negative socioaffective stimuli (i.e., the age-related positivity effect). Whether or not the effect is phylogenetically conserved is currently unknown and its biopsychosocial origins are debated. To address this gap, we evaluated how visual processing of socioaffective stimuli differs in aged, compared to middle-aged, rhesus monkeys (Macaca mulatta) using eye tracking in two experimental designs that are directly comparable to those historically used for evaluating attentional biases in humans. Results of our study demonstrate that while younger rhesus possesses robust attentional biases toward threatening pictures of conspecifics' faces, aged animals evidence no such bias. Critically, these biases emerged only when threatening faces were paired with neutral and not ostensibly "positive" faces, suggesting social context modifies the effect. Results of our study suggest that the evolutionarily shared mechanisms drive age-related decline in visual biases toward negative stimuli in aging across primate species. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Cardiac psychophysiological tuning to socioaffective content is disrupted in aged rhesus monkeys (Macaca mulatta).

Aging ushers in numerous disruptions to autonomic nervous system (ANS) function. Although the effects of aging on ANS function at rest are well characterized, there is surprising variation in reports of age-related differences in ANS reactivity to psychosocial stressors, with some reports of decreases and other reports of increases in reactivity with age. The sources of variation in age-related differences are largely unknown. Nonhuman primate models of socioaffective aging may help to uncover sources of this variation as nonhuman primates share key features of human ANS structure and function and researchers have precise control over the environments in which they age. In this report, we assess how response patterns to dynamic socioaffective stimuli in the parasympathetic and sympathetic branches of rhesus monkeys (Macaca mulatta) ANS differ in aged compared to middle-aged monkeys. We find that respiratory sinus arrhythmia, a cardiac indicator of activity in the parasympathetic branch of the ANS, exhibits age-related disruptions in responding while monkeys view videos of conspecifics. This suggests that there are evolutionarily conserved mechanisms responsible for the patterns of affective aging observed in humans and that aged rhesus monkeys are a robust translational model for human affective aging.

Effect of behavioural sampling methods on local and global social network metrics: a case-study of three macaque species.

Social network analysis (SNA) is a powerful, quantitative tool to measure animals' direct and indirect social connectedness in the context of social groups. However, the extent to which behavioural sampling methods influence SNA metrics remains unclear. To fill this gap, here we compare network indices of grooming, huddling, and aggression calculated from data collected from three macaque species through two sampling methods: focal animal sampling (FAS) and all-occurrences behaviour sampling (ABS). We found that measures of direct connectedness (degree centrality, and network density) were correlated between FAS and ABS for all social behaviours. Eigenvector and betweenness centralities were correlated for grooming and aggression networks across all species. By contrast, for huddling, we found a correlation only for betweenness centrality while eigenvector centralities were correlated only for the tolerant bonnet macaque but not so for the despotic rhesus macaque. Grooming and huddling network modularity and centralization were correlated between FAS and ABS for all but three of the eight groups. By contrast, for aggression network, we found a correlation for network centralization but not modularity between the sampling methodologies. We discuss how our findings provide researchers with new guidelines regarding choosing the appropriate sampling method to estimate social network metrics.

The importance of social behavior in nonhuman primate studies of aging: A mini-review.

Social behavior plays an important role in supporting both psychological and physical health across the lifespan. People's social lives change as they age, and the nature of these changes differ based on whether people are on healthy aging trajectories or are experiencing neurodegenerative diseases that cause dementia, such as Alzheimer's disease and Parkinson's disease. Nonhuman primate models of aging have provided a base of knowledge comparing aging trajectories in health and disease, but these studies rarely emphasize social behavior changes as a consequence of the aging process. What data exist hold particular value, as negative effects of disease and aging on social behavior are likely to have disproportionate impacts on quality of life. In this mini review, we examine the literature on nonhuman primate models of aging with a focus on social behavior, in the context of both health and disease. We propose that adopting a greater focus on social behavior outcomes in nonhuman primates will improve our understanding of the intersection of health, aging and sociality in humans.

Prenatal Zika virus infection has sex-specific effects on infant physical development and mother-infant social interactions.

There is enormous variation in the extent to which fetal Zika virus (fZIKV) infection affects the developing brain. Despite the neural consequences of fZIKV infection observed in people and animal models, many open questions about the relationship between infection dynamics and fetal and infant development remain. To further understand how ZIKV affects the developing nervous system and the behavioral consequences of prenatal infection, we adopted a nonhuman primate model of fZIKV infection in which we inoculated pregnant rhesus macaques and their fetuses with ZIKV in the early second trimester of fetal development. We then tracked their health across gestation and characterized infant development across the first month of life. ZIKV-infected pregnant mothers had long periods of viremia and mild changes to their hematological profiles. ZIKV RNA concentrations, an indicator of infection magnitude, were higher in mothers whose fetuses were male, and the magnitude of ZIKV RNA in the mothers' plasma or amniotic fluid predicted infant outcomes. The magnitude of ZIKV RNA was negatively associated with infant growth across the first month of life, affecting males' growth more than females' growth, although for most metrics, both males and females evidenced slower growth rates as compared with control animals whose mothers were not ZIKV inoculated. Compared with control infants, fZIKV infants also spent more time with their mothers during the first month of life, a social behavior difference that may have long-lasting consequences on psychosocial development during childhood.

Prenatal Zika virus exposure is associated with lateral geniculate nucleus abnormalities in juvenile rhesus macaques.

Zika virus' neural tropism causes significant neural pathology, particularly in developing fetuses. One of the consistent findings from humans and animal models is that prenatal exposure to Zika virus (ZIKV) causes pathology in the eyes and visual pathways of the brain, although the extent to which this pathology persists over development is not clear. In the present report, we build upon our previous work which demonstrated that full-term rhesus monkey ( Macaca mulatta ) fetuses who were exposed to ZIKV early in gestation had significant pathological abnormalities to the organization of the lateral geniculate nucleus (LGN), a major hub of the visual network. The objective of the present work was to replicate those LGN findings and determine whether such pathology persisted across childhood development. We carried out histological analyses of the LGNs of two juvenile rhesus monkeys who were prenatally exposed to ZIKV and two age-matched controls. Pregnant rhesus monkeys were infected with ZIKV via the intravenous and intra-amniotic routes and tracked across development. Following sacrifice and perfusion, brains were subjected to quantitative neuroanatomical analyses with a focus on the size and structure of the LGN and its composite layers. Early fetal ZIKV exposure resulted in developmental abnormalities within the brains' visual pathway: specifically disorganization, blending of layers, laminar discontinuities, and regions of low cell density within the LGN. These abnormalities were not observed in the control animals. Our findings demonstrate that the ZIKV's damage to the LGN that occurs during fetal development persists into childhood.

OpenMonkeyChallenge: Dataset and Benchmark Challenges for Pose Estimation of Non-human Primates.

The ability to automatically estimate the pose of non-human primates as they move through the world is important for several subfields in biology and biomedicine. Inspired by the recent success of computer vision models enabled by benchmark challenges (e.g., object detection), we propose a new benchmark challenge called OpenMonkeyChallenge that facilitates collective community efforts through an annual competition to build generalizable non-human primate pose estimation models. To host the benchmark challenge, we provide a new public dataset consisting of 111,529 annotated (17 body landmarks) photographs of non-human primates in naturalistic contexts obtained from various sources including the Internet, three National Primate Research Centers, and the Minnesota Zoo. Such annotated datasets will be used for the training and testing datasets to develop generalizable models with standardized evaluation metrics. We demonstrate the effectiveness of our dataset quantitatively by comparing it with existing datasets based on seven state-of-the-art pose estimation models.

The nature and neurobiology of fear and anxiety: State of the science and opportunities for accelerating discovery.

Fear and anxiety play a central role in mammalian life, and there is considerable interest in clarifying their nature, identifying their biological underpinnings, and determining their consequences for health and disease. Here we provide a roundtable discussion on the nature and biological bases of fear- and anxiety-related states, traits, and disorders. The discussants include scientists familiar with a wide variety of populations and a broad spectrum of techniques. The goal of the roundtable was to take stock of the state of the science and provide a roadmap to the next generation of fear and anxiety research. Much of the discussion centered on the key challenges facing the field, the most fruitful avenues for future research, and emerging opportunities for accelerating discovery, with implications for scientists, funders, and other stakeholders. Understanding fear and anxiety is a matter of practical importance. Anxiety disorders are a leading burden on public health and existing treatments are far from curative, underscoring the urgency of developing a deeper understanding of the factors governing threat-related emotions.

Monkeys do not show sex differences in toy preferences through their individual choices.

BACKGROUND: As interest in evaluating sex differences in nonhuman animals grows, the finding that male and female monkeys have toy preferences that differ, and that parallel those documented in human children, has garnered significant attention and is leveraged as an argument in favor of a biological contribution for human sex differences. To date, however, only two studies have investigated sex differences in monkeys' toy preferences, both documenting that males prefer toys considered to be "masculine" (such as vehicles) and females prefer toys considered to be "feminine" (such as dolls). Monkeys in these studies were tested in their social groups, making it hard to determine if the sex differences reported reflect actual individual preferences or result from social dynamics present at the time of testing. METHOD: Here, we assessed the preferences of 14 rhesus macaques (N = 7 males; N = 7 females) who were singly tested in a choice test with a variety of toys characterized as masculine (hard non-zoomorphic wheeled toys), feminine (zoomorphic soft toys), neutral (hard non-zoomorphic toys) and ambiguous (zoomorphic or plush vehicles) based on criteria from previous studies. RESULTS: Males and females showed similar preferences for neutral and "masculine" toys and preferred them (i.e., were more likely to interact with them) to "feminine" and sex-ambiguous toys. When they interacted with the toys, both males and females interacted more with neutral than with "masculine" toys. Females, but not males, interacted more with neutral and "masculine" toys than with "feminine" toys. The highest frequency of interaction for any single toy for the male monkeys was with the doll-standing is stark contrast to previous findings. CONCLUSIONS: Our results contrast greatly with the previous study in rhesus monkeys, as well as findings in human children, suggesting that the previously documented sex differences are likely context dependent, and question the existence of a strong biological basis to sex differences in toy preferences.

Reorganization in the macaque interoceptive-allostatic network following anterior cingulate cortex damage.

Accumulating evidence indicates that the adult brain is capable of significant structural change following damage-a capacity once thought to be largely limited to developing brains. To date, most existing research on adult plasticity has focused on how exteroceptive sensorimotor networks compensate for damage to preserve function. Interoceptive networks-those that represent and process sensory information about the body's internal state-are now recognized to be critical for a wide range of physiological and psychological functions from basic energy regulation to maintaining a sense of self, but the extent to which these networks remain plastic in adulthood has not been established. In this report, we used detailed histological analyses to pinpoint precise changes to gray matter volume in the interoceptive-allostatic network in adult rhesus monkeys (Macaca mulatta) who received neurotoxic lesions of the anterior cingulate cortex (ACC) and neurologically intact control monkeys. Relative to controls, monkeys with ACC lesions had significant and selective unilateral expansion of the ventral anterior insula and significant relative bilateral expansion of the lateral nucleus of the amygdala. This work demonstrates the capacity for neuroplasticity in the interoceptive-allostatic network which, given that changes included expansion rather than atrophy, is likely to represent an adaptive response following damage.

Evidence of the unidimensional structure of mind perception.

The last decade has witnessed intense interest in how people perceive the minds of other entities (humans, non-human animals, and non-living objects and forces) and how this perception impacts behavior. Despite the attention paid to the topic, the psychological structure of mind perception-that is, the underlying properties that account for variance across judgements of entities-is not clear and extant reports conflict in terms of how to understand the structure. In the present research, we evaluated the psychological structure of mind perception by having participants evaluate a wide array of human, non-human animal, and non-animal entities. Using an entirely within-participants design, varied measurement approaches, and data-driven analyses, four studies demonstrated that mind perception is best conceptualized along a single dimension.

Impact of joint interactions with humans and social interactions with conspecifics on the risk of zooanthroponotic outbreaks among wildlife populations.

Pandemics caused by pathogens that originate in wildlife highlight the importance of understanding the behavioral ecology of disease outbreaks at human-wildlife interfaces. Specifically, the relative effects of human-wildlife and wildlife-wildlife interactions on disease outbreaks among wildlife populations in urban and peri-urban environments remain unclear. We used social network analysis and epidemiological Susceptible-Infected-Recovered models to simulate zooanthroponotic outbreaks, through wild animals' joint propensities to co-interact with humans, and their social grooming of conspecifics. On 10 groups of macaques (Macaca spp.) in peri-urban environments in Asia, we collected behavioral data using event sampling of human-macaque interactions within the same time and space, and focal sampling of macaques' social interactions with conspecifics and overall anthropogenic exposure. Model-predicted outbreak sizes were related to structural features of macaques' networks. For all three species, and for both anthropogenic (co-interactions) and social (grooming) contexts, outbreak sizes were positively correlated to the network centrality of first-infected macaques. Across host species and contexts, the above effects were stronger through macaques' human co-interaction networks than through their grooming networks, particularly for rhesus and bonnet macaques. Long-tailed macaques appeared to show intraspecific variation in these effects. Our findings suggest that among wildlife in anthropogenically-impacted environments, the structure of their aggregations around anthropogenic factors makes them more vulnerable to zooanthroponotic outbreaks than their social structure. The global features of these networks that influence disease outbreaks, and their underlying socio-ecological covariates, need further investigation. Animals that consistently interact with both humans and their conspecifics are important targets for disease control.

Monkey visual attention does not fall into the uncanny valley.

Very humanlike artificial agents can induce feelings of uneasiness in human perceivers. Stimuli that generate this response are said to occupy "the uncanny valley". Given inconsistent findings in the literature, whether or not nonhuman animals experience the uncanny valley is unclear. Here, we recorded the visual attention of eleven male rhesus monkeys as they viewed faces varying in realness across five levels, with visual attention measured by both number and duration of visual fixations on faces as a whole and on areas of interest within the faces (e.g., eyes, mouth). Face stimuli varied in terms of the realism of the image and behavior depicted by the face (lipsmack, threat, bared teeth, and neutral). We largely found no support that rhesus monkeys perceive an uncanny valley when viewing our stimuli; however, monkeys did generally pay more attention to eyes and less attention to mouths in real images compared to less realistic images. Across all stimuli, monkeys' visual attention was drawn to the mouths of images when teeth were visible. These findings suggest that rhesus monkeys in our study did not display an uncanny valley effect when viewing realistic stimuli but did percieve affective information depicted by faces regardless of how real those faces appear.

Rhesus monkeys have an interoceptive sense of their beating hearts.

The sensation of internal bodily signals, such as when your stomach is contracting or your heart is beating, plays a critical role in broad biological and psychological functions ranging from homeostasis to emotional experience and self-awareness. The evolutionary origins of this capacity and, thus, the extent to which it is present in nonhuman animals remain unclear. Here, we show that rhesus monkeys (Macaca mulatta) spend significantly more time viewing stimuli presented asynchronously, as compared to synchronously, with their heartbeats. This is consistent with evidence previously shown in human infants using a nearly identical experimental paradigm, suggesting that rhesus monkeys have a human-like capacity to integrate interoceptive signals from the heart with exteroceptive audiovisual information. As no prior work has demonstrated behavioral evidence of innate cardiac interoceptive ability in nonhuman animals, these results have important implications for our understanding of the evolution of this ability and for establishing rhesus monkeys as an animal model for human interoceptive function and dysfunction. We anticipate that this work may also provide an important model for future psychiatric research, as disordered interoceptive processing is implicated in a wide variety of psychiatric conditions.

Neuroanatomical abnormalities in a nonhuman primate model of congenital Zika virus infection.

We evaluated neuropathological consequences of fetal ZIKV exposure in rhesus monkeys, a translatable animal model for human neural development, by carrying out quantitative neuroanatomical analyses of the nearly full-term brains of fetuses infected with ZIKV and procedure-matched controls. For each animal, a complete cerebral hemisphere was evaluated using immunohistochemical (IHC) and neuroanatomical techniques to detect virus, identify affected cell types, and evaluate gross neuroanatomical abnormalities. IHC staining revealed the presence of ZIKV in the frontal lobe, which contained activated microglia and showed increased apoptosis of immature neurons. ZIKV-infected animals exhibited macrostructural changes within the visual pathway. Regional differences tracked with the developmental timing of the brain, suggesting inflammatory processes related to viral infiltration swept through the cortex, followed by a wave of cell death resulting in morphological changes. These findings may help explain why some infants born with normal sized heads during the ZIKV epidemic manifest developmental challenges as they age.

Social housing status impacts rhesus monkeys' affective responding in classic threat processing tasks.

Individuals' social contexts are broadly recognized to impact both their psychology and neurobiology. These effects are observed in people and in nonhuman animals who are the subjects for comparative and translational science. The social contexts in which monkeys are reared have long been recognized to have significant impacts on affective processing. Yet, the social contexts in which monkeys live as adults are often ignored and could have important consequences for interpreting findings, particularly those related to biopsychiatry and behavioral neuroscience studies. The extant nonhuman primate neuropsychological literature has historically tested individually-housed monkeys, creating a critical need to understand how social context might impact the outcomes of such experiments. We evaluated affective responding in adult rhesus monkeys living in four different social contexts using two classic threat processing tasks-a test of responsivity to objects and a test of responsivity to an unfamiliar human. These tasks have been commonly used in behavioral neuroscience for decades. Relative to monkeys with full access to a social partner, individually-housed monkeys had blunted reactivity to threat and monkeys who had limited contact with their partner were more reactive to some threatening stimuli. These results indicate that monkeys' social housing contexts impact affective reactivity and point to the potential need to reconsider inferences drawn from prior studies in which the impacts of social context have not been considered.

Amygdala or hippocampus damage only minimally impacts affective responding to threat.

Decades of research studying the behavioral effects of damage to structures in medial temporal lobe of rhesus monkeys have documented that such damage, particularly damage to the amygdala, causes animals to become hyporesponsive to threat and hyper-social. This phenotype, a subset of the behaviors known as "Klüver-Bucy Syndrome," is one of the most well-known phenomena in behavioral neuroscience. Carrying on the tradition of evaluating hyposensitivity to threat in monkeys with temporal lobe lesions, we evaluated the responses of rhesus monkeys with bilateral ibotenic acid lesions of the amygdala or hippocampus and procedure-matched control animals to the presentation of an unfamiliar human intruder and threatening objects of varying complexity. All animals behaved as expected-calibrating their responses to the ostensible threat value of the stimuli such that they were most responsive to the most potent stimuli and least responsive to the least potent stimuli. Contrary to an earlier report (Mason et al., 2006), lesion status did not impact the pattern of responses across multiple dependent measures (overt behaviors, position in cage, etc.). The only lesion induced difference consistent with hyposensitivity to threat was that monkeys with amygdala lesions retrieved food rewards placed near reptile-like objects more rapidly than did control animals. These findings call into question the assumption that amygdala damage causes robust, stereotyped changes to affective behavior. They also highlight the importance of replication in neuroscientific studies using nonhuman primates. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A pragmatic reevaluation of the efficacy of nonhuman primate optogenetics for psychiatry.

Translational neuroscience is committed to generating discoveries in the laboratory that ultimately can improve human lives. Optogenetics has received considerable attention because of its demonstrated promise in rodent brains to manipulate cells and circuits. In a recent report, Tremblay et al. [28] introduce an open resource detailing optogenetic studies of the nonhuman primate (NHP) brain and make robust claims about the translatability of the technology. We propose that their quantitative (e.g. a 91% success rate) and theoretical claims are questionable because the data were analyzed at a level relevant to the rodent but not NHP brain. Injections were clustered within a few monkeys in a few studies in a few brain regions, and their definitions of success were not clearly relevant to human neuropsychiatric disease. A reanalysis of the data with a modified definition of success that included a behavioral and biological effect revealed a 62.5% success rate that was lower when considering only strong outcomes (53.1%). This calls into question the current efficacy of optogenetic techniques in the NHP brain and suggests that we are a long way from being able to leverage them in 'the service of patients with neurological or psychiatric conditions' as the Tremblay report claims.

Improving rigor and reproducibility in nonhuman primate research.

Nonhuman primates (NHPs) are a critical component of translational/preclinical biomedical research due to the strong similarities between NHP and human physiology and disease pathology. In some cases, NHPs represent the most appropriate, or even the only, animal model for complex metabolic, neurological, and infectious diseases. The increased demand for and limited availability of these valuable research subjects requires that rigor and reproducibility be a prime consideration to ensure the maximal utility of this scarce resource. Here, we discuss a number of approaches that collectively can contribute to enhanced rigor and reproducibility in NHP research.