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Biology subjects

Platt, M. L.

Publications and source records attributed to Platt, M. L..

18 recordsLinked to original sources

Trait anxiety drives premature disengagement despite intact opportunity-cost sensitivity

Anxiety has been linked to difficulty sustaining engagement with ongoing tasks, even when continued engagement would yield greater rewards, yet the underlying mechanisms remain unclear. Here we examined how trait anxiety shapes sequential foraging decisions using a patch-leaving task grounded in the Marginal Value Theorem (MVT), a normative framework for explore-exploit decisions previously used to reveal altered computations in conditions such as problem gambling and attention-deficit hyperactivity disorder. Across two independent cohorts, participants adjusted patch residence times according to environmental opportunity costs, indicating preserved sensitivity to task structure irrespective of anxiety levels. Despite this, individuals with higher trait anxiety consistently left patches earlier and accrued fewer rewards. Drift diffusion modeling revealed that these deviations arose from reduced reward-driven evidence accumulation, rather than impaired environmental sensitivity or altered learning: trait anxiety reliably reduced the drift rate governing continued exploitation, providing a computational account of premature disengagement. This effect remained robust after accounting for pupil-linked arousal and baseline stress biomarkers, including salivary -amylase and cortisol, which independently constrained decision dynamics. Together, these findings identify reduced reward-evidence accumulation as a core mechanism through which anxiety promotes premature disengagement from rewarding environments.

neuroscience↗

Attenuation of value-to-evidence translation drives biased decision making in anxiety and depression

Anxiety and depression are globally prevalent conditions associated with maladaptive decision making. However, whether affective symptoms primarily amplify threat avoidance or dampen motivational drive remains debated, and behavioural studies yield inconsistent findings. Here we show that both anxiety and depression impair the fundamental cognitive process of translating objective value into decision evidence. Across independent cohorts from the US and India, participants evaluated risky gambles while we assessed choice behaviour and the centroparietal positivity, an EEG marker of accumulating decision evidence. Prospect theory parameters, like risk and loss aversion, showed little association with symptom severity. Conversely, hierarchical drift-diffusion modelling revealed that higher symptom scores predicted attenuated value sensitivity during evidence accumulation, whereas decision caution remained intact. This reduction in value sensitivity suggests internalizing symptoms disrupt choice at the value-to-evidence interface, offering a unified mechanism underlying biased decision making in affective disorders.

neuroscience↗

Mid-superior temporal sulcus encodes spatial context and behavioral state in freely moving macaques

Primate neuroscience has traditionally studied the brain under highly constrained conditions, limiting our understanding of neural function during real-world behavior. The mid-superior temporal sulcus (mSTS) is implicated in social perception, but its role during unconstrained behavior has not been tested. Here we performed wireless depth-electrode recordings from both banks of mSTS in macaques freely exploring a large three-dimensional arena, combined with 3D pose tracking and behavioral segmentation. Neural encoding models revealed mSTS firing rates were jointly modulated by spatial position, body kinematics, and geometric visual proxies, preferentially encoded in allocentric coordinates but with a shift toward body-centric encoding during vertical exploration. Neural populations carried decodable information about discrete behavioral syllables, with broad temporal generalization and neural similarity that tracked the sequential structure of behavior. Population manifold analysis revealed that the same behavior occupied different regions of population space at different spatial locations, and population dynamics showed structured organization around behavioral transitions. Together, these results suggest that mSTS populations carry joint information about spatial context and behavioral state during natural behavior.

neuroscience↗

Age and early life adversity shape heterogeneity of the epigenome across tissues in macaques

Age and early life adversity (ELA) are both key determinants of health, but whether they target similar physiological mechanisms across the body is unknown due to limited multi-tissue datasets from well-characterized cohorts. We generated DNA methylation (DNAm) profiles across 14 tissues in 237 semi-free ranging rhesus macaques, with records of naturally occurring ELA. We show that age-associated DNAm variation is predominantly tissue-dependent, yet tissue-specific epigenetic clocks reveal that the pace of epigenetic aging is relatively consistent within individuals. ELA effects on loci are adversity-dependent, but a given ELA has a coordinated impact across tissues. Finally, ELA targeted many of the same loci as age, but the direction of these effects varied, indicating that ELA does not uniformly contribute to accelerated age in the epigenome. ELA thus imprints a coordinated, tissue-spanning epigenetic signature that is both distinct from and intertwined with age-related change, advancing our understanding of how early environments sculpt the molecular foundations of aging and disease.

genomics↗

Multi-dimensional social relationships shape social attention in monkeys

Social relationships guide individual behavior and ultimately shape the fabric of society. Primates exhibit particularly complex, differentiated, and multidimensional social relationships, which form interwoven social networks, reflecting both individual social tendencies and specific dyadic interactions. How the patterns of behavior that underlie these social relationships emerge from moment-to-moment patterns of social information processing remains unclear. Here, we assess social relationships among a group of four monkeys, focusing on aggression, grooming, and proximity. We show that individual differences in social attention vary with individual differences in patterns of general social tendencies and patterns of individual engagement with specific partners. Oxytocin administration altered social attention and its relationship to both social tendencies and dyadic relationships, particularly grooming and aggression. Our findings link the dynamics of visual information sampling to the dynamics of primate social networks.

neuroscience↗

Social ageing can protect against infectious disease in a group-living primate

The benefits of social living are well established, but sociality also comes with costs, including infectious disease risk. This cost-benefit ratio of sociality is expected to change across individuals lifespans, which may drive changes in social behaviour with age. To explore this idea, we combine data from a group-living primate for which social ageing has been described with epidemiological models to show that having lower social connectedness when older can protect against the costs of a hypothetical, directly transmitted endemic pathogen. Assuming no age differences in epidemiological characteristics (susceptibility to, severity, and duration of infection), older individuals suffered lower infection costs, which was explained largely because they were less connected in their social networks than younger individuals. This benefit of social ageing depended on epidemiological characteristics and was greatest when infection severity increased with age. When infection duration increased with age, social ageing was beneficial only when pathogen transmissibility was low. Older individuals benefited most from having a lower frequency of interactions (strength) and network embeddedness (closeness) and benefited less from having fewer social partners (degree). Our study provides a first examination of the epidemiology of social ageing, demonstrating the potential for pathogens to influence evolutionary dynamics of social ageing in natural populations.

animal behavior and cognition↗

Taking identity-by-descent analysis into the wild: Estimating realized relatedness in free-ranging macaques

Biological relatedness is a key consideration in studies of behavior, population structure, and trait evolution. Except for parent-offspring dyads, pedigrees capture relatedness imperfectly. The number and length of DNA segments that are identical-by-descent (IBD) yield the most precise estimates of relatedness. Here, we leverage novel methods for estimating locus-specific IBD from low coverage whole genome resequencing data to demonstrate the feasibility and value of resolving fine-scaled gradients of relatedness in free-living animals. Using primarily 4-6x coverage data from a rhesus macaque (Macaca mulatta) population with available long-term pedigree data, we show that we can call the number and length of IBD segments across the genome with high accuracy even at 0.5x coverage. The resulting estimates demonstrate substantial variation in genetic relatedness within kin classes, leading to overlapping distributions between kin classes. They identify cryptic genetic relatives that are not represented in the pedigree and reveal elevated recombination rates in females relative to males, which allows us to discriminate maternal and paternal kin using genotype data alone. Our findings represent a breakthrough in the ability to understand the predictors and consequences of genetic relatedness in natural populations, contributing to our understanding of a fundamental component of population structure in the wild.

ecology↗

Information gathering explains decision dynamics during human and monkey reward foraging

Foraging in humans and other animals requires a delicate balance between exploitation of current resources and exploration for new ones. The tendency to overharvest--lingering too long in depleting patches--is a routine behavioral deviation from predictions of optimal foraging theories. To characterize the computational mechanisms driving these deviations, we modeled foraging behavior using a virtual patch-leaving task with human participants and validated our findings in an analogous foraging task in two monkeys. Both humans and monkeys overharvested and stayed longer in patches with longer travel times compared to shorter ones. Critically, patch residence times in both species declined over the course of sessions, enhancing reward rates in humans. These decisions were best explained by a logistic transformation that integrated both current rewards and information about declining rewards. This parsimonious model demystifies both the occurrence and dynamics of overharvesting, highlighting the role of information gathering in foraging. Our findings provide insight into computational mechanisms shaped by ubiquitous foraging dilemmas, underscoring how behavioral modeling can reveal underlying motivations of seemingly irrational decisions.

animal behavior and cognition↗

The biology of aging in a social world: insights from free-ranging rhesus macaques

Social adversity can increase the age-associated risk of disease and death, yet the biological mechanisms that link social adversities to aging remain poorly understood. Long-term naturalistic studies of nonhuman animals are crucial for integrating observations of social behavior throughout an individuals life with detailed anatomical, physiological, and molecular measurements. Here, we synthesize the body of research from one such naturalistic study system, Cayo Santiago Island, which is home to the worlds longest continuously monitored free-ranging population of rhesus macaques. We review recent studies of age-related variation in morphology, gene regulation, microbiome composition, and immune function. We also discuss ecological and social modifiers of age-markers in this population. In particular, we summarize how a major natural disaster, Hurricane Maria, affected rhesus macaque physiology and social structure and highlight the context-dependent and domain-specific nature of aging modifiers. Finally, we conclude by providing directions for future study, on Cayo Santiago and elsewhere, that will further our understanding of aging across different domains and how social adversity modifies aging processes.

immunology↗

A generalizable epigenetic clock captures aging in two nonhuman primates.

Epigenetic clocks generated from DNA methylation array data provide important insights into biological aging, disease susceptibility, and mortality risk. However, these clocks cannot be applied to high-throughput, sequence-based datasets more commonly used to study nonhuman animals. Here, we built a generalizable epigenetic clock using genome-wide DNA methylation data from 493 free-ranging rhesus macaques. Using a sliding-window approach that maximizes generalizability across datasets and species, this model predicted age with high accuracy ({+/-} 1.42 years) in held-out test samples, as well as in two independent test sets: rhesus macaques from a captive population (n=43) and wild baboons in Kenya (n=271). Our model can also be used to generate insight into the factors hypothesized to alter epigenetic aging, including social status and exposure to traumatic events. Our results thus provide a flexible tool for predicting age in other populations and species and illustrate how connecting behavioral data with the epigenetic clock can uncover social influences on biological age.

evolutionary biology↗

Evolutionary and biomedical implications of sex differences in the primate brain transcriptome

Humans exhibit sex differences in the prevalence of many neurodevelopmental and neurodegenerative conditions. To better understand the translatability of a critical nonhuman primate model, the rhesus macaque, we generated one of the largest multibrain region bulk transcriptional datasets for this species and characterized sex-biased gene expression patterns. We demonstrate that these patterns are similar to those in humans and are associated with overlapping regulatory mechanisms, biological processes, and genes implicated in sex-biased human disorders, including autism. We also show that sex-biased genes exhibit greater genetic variance for expression and more tissue-specific expression patterns, which may facilitate the rapid evolution of sex-biased genes. Our findings provide insights into the biological mechanisms underlying sex-biased disease and validate the rhesus macaque model for the study of these conditions.

neuroscience↗

A single-cell multi-omic atlas spanning the adult rhesus macaque brain

Cataloging the diverse cellular architecture of the primate brain is crucial for understanding cognition, behavior and disease in humans. Here, we generated a brain-wide single-cell multimodal molecular atlas of the rhesus macaque brain. Altogether, we profiled 2.58M transcriptomes and 1.59M epigenomes from single nuclei sampled from 30 regions across the adult brain. Cell composition differed extensively across the brain, revealing cellular signatures of region-specific functions. We also identified 1.19M candidate regulatory elements, many novel, allowing us to explore the landscape of cis-regulatory grammar and neurological disease risk in a cell-type-specific manner. Together, this multi-omic atlas provides an open resource for investigating the evolution of the human brain and identifying novel targets for disease interventions.

neuroscience↗

Ageing in a collective: The impact of ageing individuals on social network structure

Ageing affects many phenotypic traits, but its consequences for social behaviour have only recently become apparent. Social networks emerge from associations between individuals. The changes in sociality that occur as individuals get older are thus likely to impact network structure, yet this remains unstudied. Here we use empirical data from free-ranging rhesus macaques and an agent-based model to test how age-based changes in social behaviour feed up to influence: (1) an individuals level of indirect connectedness in their network; and (2) overall patterns of network structure. Our empirical analyses revealed that female macaques became less indirectly connected as they aged for some, but not all network measures examined, suggesting that indirect connectivity is affected by ageing, and that ageing animals can remain well integrated in some social contexts. Surprisingly, we did not find evidence for a relationship between age distribution and the structure of female macaque networks. We used an agent-based model to gain further understanding of the link between age-based differences in sociality and global network structure, and under which circumstances global effects may be detectable. Overall, our results suggest a potentially important and underappreciated role of age in the structure and function of animal collectives, which warrants further investigation.

animal behavior and cognition↗

Sociodemographic effects on immune cell composition in a free-ranging non-human primate.

Increasing age is associated with dysregulated immune function and increased inflammation- patterns that are also observed in individuals exposed to chronic social adversity. Yet we still know little about how social adversity impacts the immune system and how it might promote age-related diseases. Here, we investigated how immune cell diversity varied with age, sex and social adversity (operationalized as low social status) in free-ranging rhesus macaques. We found age-related signatures of immunosenescence, including lower proportions of CD20+ B cells, CD20+/CD3+ ratio, and CD4+/CD8+ T cell ratio - all signs of diminished antibody production. Age was associated with higher proportions of CD3+/CD8+ Cytotoxic T cells, CD16+/CD3-Natural Killer cells, CD3+/CD4+/CD25+ and CD3+/CD8+/CD25+ T regulatory cells, and CD14+/CD16+/HLA-DR+ intermediate monocytes, and lower levels of CD14+/CD16-/HLA-DR+ classical monocytes, indicating greater amounts of inflammation and immune dysregulation. We also found an effect of exposure to social adversity (i.e., low social status) that was sex-dependent. High-status males, relative to females, had higher CD20+/CD3+ ratios and CD16+/CD3 Natural Killer cell proportions, and lower proportions of CD8+ Cytotoxic T cells. Further, low status females had higher proportions of cytotoxic T cells than high status females, while the opposite was observed in males. High status males had higher CD20+/CD3+ ratios than low status males. Together, our study identifies immune cell types that differ by age in a human-relevant primate model animal, and demonstrates a novel link between sex-dependent immunity and social adversity.

immunology↗

Rhesus macaques as a tractable physiological model of human ageing

Research in the basic biology of ageing is increasingly identifying mechanisms and modifiers of ageing in short-lived organisms such as worms and mice. The ultimate goal of such work is to improve human health, particularly in the growing segment of the population surviving into old age. Thus far, few interventions have robustly transcended species boundaries in the laboratory, suggesting that changes in approach are needed to avoid costly failures in translational human research. In this review, we discuss both well-established and alternative model organisms for ageing research and outline how research in nonhuman primates is sorely needed, first, to translate findings from shorter-lived organisms to humans, and second, to understand key aspects of ageing that are unique to primate biology. We focus on rhesus macaques as a particularly promising model organism for ageing research due to their social and physiological similarity to humans as well as the existence of key resources that have been developed for this species. As a case study, we compare gene regulatory signatures of ageing in the peripheral immune system between humans and rhesus macaques from a free-ranging study population in Cayo Santiago. We show that both mRNA expression and DNA methylation signatures of immune ageing are broadly shared between macaques and humans, indicating strong conservation of the trajectory of ageing in the immune system. We conclude with a review of key issues in the biology of ageing for which macaques and other nonhuman primates may uniquely contribute valuable insights, including the effects of social gradients on health and ageing. We anticipate that continuing research in rhesus macaques and other nonhuman primates will play a critical role in conjunction with model organism and human biodemographic research in ultimately improving translational outcomes and extending health and longevity in our ageing population.

genomics↗

A machine learning approach to identifying objectivebiomarkers of anxiety and stress

Anxiety and stress-related disorders are highly prevalent and debilitating conditions that impose an enormous burden on society. Sensitive measurements that can enable early diagnosis could mitigate suffering and potentially prevent onset of these conditions. Self-reports, however, are intrusive and vulnerable to biases that can conceal the true internal state. Physiological responses, on the other hand, manifest spontaneously and can be monitored continuously, providing potential objective biomarkers for anxiety and stress. Recent studies have shown that algorithms trained on physiological measurements can predict stress states with high accuracy. Whether these predictive algorithms generalize to untested situations and participants, however, remains unclear. Further, whether biomarkers of momentary stress indicate trait anxiety - a vulnerability foreshadowing development of anxiety and mood disorders - remains unknown. To address these gaps, we monitored skin conductance, heart rate, heart rate variability and EEG in 39 participants experiencing physical and social stress and compared these measures to non-stressful periods of talking, rest, and playing a simple video game. Self-report measures were obtained periodically throughout the experiment. A support vector machine trained on physiological measurements identified stress conditions with ~96% accuracy. A decision tree that optimally combined physiological and self-report measures identified individuals with high trait anxiety with ~84% accuracy. Individuals with high trait anxiety also displayed high baseline state anxiety but a muted physiological response to acute stressors. Overall, these results demonstrate the potential for using machine learning tools to identify objective biomarkers useful for diagnosing and monitoring mental health conditions like anxiety and depression.

neuroscience↗

Neuronal activity in the posterior cingulate cortex signals environmental information and predicts behavioral variability during routine foraging

Animals engage in routine behavior in order to efficiently navigate their environments. This routine behavior may be influenced by the state of the environment, such as the location and size of rewards. The neural circuits tracking environmental information and how that information impacts decisions to diverge from routines remains unexplored. To investigate the representation of environmental information during routine foraging, we recorded the activity of single neurons in posterior cingulate cortex (PCC) in monkeys searching through an array of targets in which the location of rewards was unknown. Outside the laboratory, people and animals solve such traveling salesman problems by following routine traplines that connect nearest-neighbor locations. In our task, monkeys also deployed traplining routines, but as the environment became better known, they diverged from them despite the reduction in foraging efficiency. While foraging, PCC neurons tracked environmental information but not reward and predicted variability in the pattern of choices. Together, these findings suggest that PCC mediates the influence of information on variability in choice behavior.

neuroscience↗

Neuronal Mechanisms of Strategic Cooperation

Here we demonstrate that during strategic gameplay monkeys behave as if they reason recursively about other individuals beliefs and desires in order to predict their choices and to guide their own actions, especially the decision to cooperate. Neurons in mid superior temporal sulcus (mSTS), the putative homolog of the human temporo-parietal junction (TPJ), signal abstract non-perceptual social information, including payoffs, intentions, and outcomes, and further distinguish between social and nonsocial agents while monkeys play the game. We demonstrate for the first time that a subpopulation of these neurons selectively signals cooperatively obtained rewards. Neurons in the anterior cingulate gyrus (ACCg), an area implicated in vicarious reinforcement and empathy, do not distinguish agency and as a population carry less information about strategic variables. These findings suggest the capacity to mentalize has deep roots in the strategic social behavior of primates, and endorse mSTS as the evolutionary wellspring of these functions.

neuroscience↗