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.

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.

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.

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.

Anterior Cingulate Cortex Ablation Disrupts Affective Vigor and Vigilance.

Despite many observations of anterior cingulate cortex (ACC) activity related to cognition and affect in humans and nonhuman animals, little is known about the causal role of the ACC in psychological processes. Here, we investigate the causal role of the ACC in affective responding to threat in rhesus monkeys (Macaca mulatta), a species with an ACC largely homologous to humans in structure and connectivity. Male adult monkeys received bilateral ibotenate axon-sparing lesions to the ACC (sulcus and gyrus of areas 24, 32, and 25) and were tested in two classic tasks of monkey threat processing: the human intruder and object responsiveness tasks. Monkeys with ACC lesions did not significantly differ from controls in their overall mean reactivity toward threatening or novel stimuli. However, while control monkeys maintained their reactivity across test days, monkeys with ACC lesions reduced their reactivity toward stimuli as days advanced. Critically, this attenuated reactivity was found even when the stimuli presented each day were novel, suggesting that ACC lesions did not simply cause accelerated adaptation to stimuli as they became less novel over repeated presentations. Rather, these results imply that the primate ACC is necessary for maintaining appropriate affective responses toward potentially harmful and/or novel stimuli. These findings therefore have implications for mood disorders in which responding to threat and novelty is disrupted.SIGNIFICANCE STATEMENT Decades of research in humans and nonhuman animals have investigated the role of the anterior cingulate cortex in a huge number and variety of psychological processes spanning cognition and affect, as well as in psychological and neurologic diseases. The structure is broadly implicated in psychological processes and mental and neurologic health, yet its causal role in these processes has largely gone untested, particularly in primates. Here we demonstrate that when anterior cingulate cortex is completely eliminated, rhesus monkeys are initially responsive to threats, but these responses attenuate rather than persist, resembling a pattern of behavior commonly seen in patients diagnosed with mood disorders.

Oligomeric Aß in the monkey brain impacts synaptic integrity and induces accelerated cortical aging.

As the average age of the population continues to rise, the number of individuals affected with age-related cognitive decline and Alzheimer's disease (AD) has increased and is projected to cost more than $290 billion in the United States in 2019. Despite significant investment in research over the last decades, there is no effective treatment to prevent or delay AD progression. There is a translational gap in AD research, with promising drugs based on work in rodent models failing in clinical trials. Aging is the leading risk factor for developing AD and understanding neurobiological changes that affect synaptic integrity with aging will help clarify why the aged brain is vulnerable to AD. We describe here the development of a rhesus monkey model of AD using soluble oligomers of the amyloid beta (Aß) peptide (AßOs). AßOs infused into the monkey brain target a specific population of spines in the prefrontal cortex, induce neuroinflammation, and increase AD biomarkers in the cerebrospinal fluid to similar levels observed in patients with AD. Importantly, AßOs lead to similar dendritic spine loss to that observed in normal aging in monkeys, but so far without detection of amyloid plaques or tau pathology. Understanding the basis of synaptic impairment is the most effective route to early intervention and prevention or postponement of age-related cognitive decline and transition to AD. These initial findings support the use of monkeys as a platform to understand age-related vulnerabilities of the primate brain and may help develop effective disease-modifying therapies for treatment of AD and related dementias.

Structural differences in the hippocampus and amygdala of behaviorally inhibited macaque monkeys.

Behavioral inhibition is a temperamental disposition to react warily when confronted by unfamiliar people, objects, or events. Behaviorally inhibited children are at greater risk of developing anxiety disorders later in life. Previous studies reported that individuals with a history of childhood behavioral inhibition exhibit abnormal activity in the hippocampus and amygdala. However, few studies have investigated the structural differences that may underlie these functional abnormalities. In this exploratory study, we evaluated rhesus monkeys exhibiting a phenotype consistent with human behavioral inhibition. We performed quantitative neuroanatomical analyses that cannot be performed in humans including estimates of the volume and neuron number of distinct hippocampal regions and amygdala nuclei in behaviorally inhibited and control rhesus monkeys. Behaviorally inhibited monkeys had larger volumes of the rostral third of the hippocampal field CA3, smaller volumes of the rostral third of CA2, and smaller volumes of the accessory basal nucleus of the amygdala. Furthermore, behaviorally inhibited monkeys had fewer neurons in the rostral third of CA2. These structural differences may contribute to the functional abnormalities in the hippocampus and amygdala of behaviorally inhibited individuals. These structural findings in monkeys are consistent with a reduced modulation of amygdala activity via prefrontal cortex projections to the accessory basal nucleus. Given the putative roles of the amygdala in affective processing, CA3 in associative learning and CA2 in social memory, increased amygdala and CA3 activity, and diminished CA2 structure and function, may be associated with increased social anxiety and the heritability of behavioral inhibition. The findings from this exploratory study compel follow-up investigations with larger sample sizes and additional analyses to provide greater insight and more definitive answers regarding the neurobiological bases of behavioral inhibition.

Implementing social network analysis to understand the socioecology of wildlife co-occurrence and joint interactions with humans in anthropogenic environments.

Human population expansion into wildlife habitats has increased interest in the behavioural ecology of human-wildlife interactions. To date, however, the socioecological factors that determine whether, when or where wild animals take risks by interacting with humans and anthropogenic factors still remains unclear. We adopt a comparative approach to address this gap, using social network analysis (SNA). SNA, increasingly implemented to determine human impact on wildlife ecology, can be a powerful tool to understand how animal socioecology influences the spatiotemporal distribution of human-wildlife interactions. For 10 groups of rhesus, long-tailed and bonnet macaques (Macaca spp.) living in anthropogenically impacted environments in Asia, we collected data on human-macaque interactions, animal demographics, and macaque-macaque agonistic and affiliative social interactions. We constructed 'human co-interaction networks' based on associations between macaques that interacted with humans within the same time and spatial locations, and social networks based on macaque-macaque allogrooming behaviour, affiliative behaviours of short duration (agonistic support, lip-smacking, silent bare-teeth displays and non-sexual mounting) and proximity. Pre-network permutation tests revealed that, within all macaque groups, specific individuals jointly took risks by repeatedly, consistently co-interacting with humans within and across time and space. GLMMs revealed that macaques' tendencies to co-interact with humans was positively predicted by their tendencies to engage in short-duration affiliative interactions and tolerance of conspecifics, although the latter varied across species (bonnets>rhesus>long-tailed). Male macaques were more likely to co-interact with humans than females. Neither macaques' grooming relationships nor their dominance ranks predicted their tendencies to co-interact with humans. Our findings suggest that, in challenging anthropogenic environments, less (compared to more) time-consuming forms of affiliation, and additionally greater social tolerance in less ecologically flexible species with a shorter history of exposure to humans, may be key to animals' joint propensities to take risks to gain access to resources. For males, greater exploratory tendencies and less energetically demanding long-term life-history strategies (compared to females) may also influence such joint risk-taking. From conservation and public health perspectives, wildlife connectedness within such co-interaction networks may inform interventions to mitigate zoonosis, and move human-wildlife interactions from conflict towards coexistence.

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.

Impact of anthropogenic factors on affiliative behaviors among bonnet macaques.

OBJECTIVES: In primates, allogrooming and other affiliative behaviors confer many benefits and may be influenced by many socioecological factors. Of these, the impact of anthropogenic factors remain relatively understudied. Here we ask whether interactions with humans decreased macaques' affiliative behaviors by imposing time-constraints, or increased these behaviors on account of more free-/available-time due to macaques' consumption of high-energy human foods. MATERIALS AND METHODS: In Southern India, we collected data on human-macaque and macaque-macaque interactions using focal-animal sampling on two groups of semi-urban bonnet macaques for 11 months. For each macaque within each climatic season, we calculated frequencies of human-macaque interactions, rates of monitoring human activity and foraging on anthropogenic food, dominance ranks, grooming duration, number of unique grooming partners, and frequencies of other affiliative interactions. RESULTS: We found strong evidence for time-constraints on grooming. Macaques that monitored humans more groomed for shorter durations and groomed fewer partners, independent of their group membership, sex, dominance rank, and season. However, monitoring humans had no impact on other affiliative interactions. We found no evidence for the free-time hypothesis: foraging on anthropogenic food was unrelated to grooming and other affiliation. DISCUSSION: Our results are consistent with recent findings on other urban-dwelling species/populations. Macaques in such environments may be especially reliant on other forms of affiliation that are of short duration (e.g., coalitionary support, lip-smacking) and unaffected by time-constraints. We stress on the importance of evaluating human impact on inter-individual differences in primate/wildlife behavior for conservation efforts.

Rates of human-macaque interactions affect grooming behavior among urban-dwelling rhesus macaques (Macaca mulatta).

OBJECTIVES: The impact of anthropogenic environmental changes may impose strong pressures on the behavioral flexibility of free-ranging animals. Here, we examine whether rates of interactions with humans had both a direct and indirect influence on the duration and distribution of social grooming in commensal rhesus macaques (Macaca mulatta). MATERIALS AND METHODS: Data were collected in two locations in the city of Shimla in northern India: an urban setting and a temple area. We divided these two locations in a series of similar-sized physical blocks (N = 48) with varying rates of human-macaque interactions. We conducted focal observations on three free-ranging rhesus macaque groups, one in the urban area and two in the temple area. RESULTS: Our analysis shows that macaques engaged in shorter grooming bouts and were more vigilant while grooming in focal sessions during which they interacted with people more frequently, suggesting that humans directly affected grooming effort and vigilance behavior. Furthermore, we found that in blocks characterized by higher rates of human-macaque interactions grooming bouts were shorter, more frequently interrupted by vigilance behavior, and were less frequently reciprocated. DISCUSSION: Our work shows that the rates of human-macaque interaction had both a direct and indirect impact on grooming behavior and that macaques flexibly modified their grooming interactions in relation to the rates of human-macaque interaction to which they were exposed. Because grooming has important social and hygienic functions in nonhuman primates, our work suggests that human presence can have important implications for animal health, social relationships and, ultimately, fitness. Our results point to the need of areas away from people even for highly adaptable species where they can engage in social interactions without human disruption.

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.

Laboratory rhesus macaque social housing and social changes: Implications for research.

Macaque species, specifically rhesus (Macaca mulatta), are the most common nonhuman primates (NHPs) used in biomedical research due to their suitability as a model of high priority diseases (e.g., HIV, obesity, cognitive aging), cost effective breeding and housing compared to most other NHPs, and close evolutionary relationship to humans. With this close evolutionary relationship, however, is a shared adaptation for a socially stimulating environment, without which both their welfare and suitability as a research model are compromised. While outdoor social group housing provides the best approximation of a social environment that matches the macaque behavioral biology in the wild, this is not always possible at all facilities, where animals may be housed indoors in small groups, in pairs, or alone. Further, animals may experience many housing changes in their lifetime depending on project needs, changes in social status, management needs, or health concerns. Here, we review the evidence for the physiological and health effects of social housing changes and the potential impacts on research outcomes for studies using macaques, particularly rhesus. We situate our review in the context of increasing regulatory pressure for research facilities to both house NHPs socially and mitigate trauma from social aggression. To meet these regulatory requirements and further refine the macaque model for research, significant advances must be made in our understanding and management of rhesus macaque social housing, particularly pair-housing since it is the most common social housing configuration for macaques while on research projects. Because most NHPs are adapted for sociality, a social context is likely important for improving repeatability, reproducibility, and external validity of primate biomedical research. Am. J. Primatol. 79:e22528, 2017. © 2016 Wiley Periodicals, Inc.

Maternal rearing environment impacts autonomic nervous system activity.

While it is now well known that social deprivation during early development permanently perturbs affective responding, accumulating evidence suggests that less severe restriction of the early social environment may also have deleterious effects. In the present report, we evaluate the affective responding of rhesus macaque (Macaca mulatta) infants raised by their mothers in restricted social environments or by their mothers in large social groups by indexing autonomic nervous system activity. Following a 25-hr evaluation of biobehavioral organization, electrocardiogram, and an index of respiration were recorded for 10 min. This allowed for an evaluation of both heart rate and respiratory sinus arrhythmia (RSA), an index of parasympathetic activity, during a challenging situation. Three- to four-month-old infants raised in restricted social environments had significantly higher heart rates and lower RSA as compared to infants raised in unrestricted social environments, consistent with a more potent stress response to the procedure. These results are consistent with mounting evidence that the environment in which individuals are raised has important consequences for affective processing.

A ventral salience network in the macaque brain.

Successful navigation of the environment requires attending and responding efficiently to objects and conspecifics with the potential to benefit or harm (i.e., that have value). In humans, this function is subserved by a distributed large-scale neural network called the "salience network". We have recently demonstrated that there are two anatomically and functionally dissociable salience networks anchored in the dorsal and ventral portions of the human anterior insula (Touroutoglou et al., 2012). In this paper, we test the hypothesis that these two subnetworks exist in rhesus macaques (Macaca mulatta). We provide evidence that a homologous ventral salience network exists in macaques, but that the connectivity of the dorsal anterior insula in macaques is not sufficiently developed as a dorsal salience network. The evolutionary implications of these finding are considered.

Knowing your heart and your mind: The relationships between metamemory and interoception.

Humans experience a unified self that integrates our mental lives and physical bodies, but many studies focus on isolated domains of self-knowledge. We tested the hypothesis that knowledge of one's mind and body are related by examining metamemory and interoception. We evaluated two dimensions of metamemory and interoception: subjective beliefs and the accuracy of those beliefs compared to objective criteria. We first demonstrated, in two studies, that metamemory beliefs were positively correlated with interoceptive beliefs, and this was not due to domain-general confidence. Finally, we showed that individuals with better metamemory accuracy also had better interoceptive accuracy. Taken together, these findings suggest a common mechanism subserving knowledge of our cognitive and bodily states.

Humans are ultrasocial and emotional.

Given the highly social nature of the human emotion system, it is likely that it subserved the evolution of ultrasociality. We review how the experience and functions of human emotions enable social processes that promote ultrasociality (e.g., cooperation). We also point out that emotion may represent one route to redress one of the negative consequences of ultrasociality: ecosystem domination.

Tag, you're it: affect tagging promotes goal formation and selection.

Building upon Huang & Bargh's (H&B's) theory, we propose a complementary view that goal formation and selection are both supported by affect. We suggest that goals may form when affect "tags" discrete behaviors and their outcomes. Further, we propose that goal-associated affect may help guide selection between competing goals, for example, in the case of short-term and long-term goals.

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).