Neural signatures of natural behaviour in socializing macaques.

Our understanding of the neurobiology of primate behaviour largely derives from artificial tasks in highly controlled laboratory settings, overlooking most natural behaviours that primate brains evolved to produce1-3. How primates navigate the multidimensional social relationships that structure daily life4 and shape survival and reproductive success5 remains largely unclear at the single-neuron level. Here we combine ethological analysis, computer vision and wireless recording technologies to identify neural signatures of natural behaviour in unrestrained, socially interacting pairs of rhesus macaques. Single-neuron and population activity in the prefrontal and temporal cortex robustly encoded 24 species-typical behaviours, as well as social context. Male-female partners demonstrated near-perfect reciprocity in grooming, a key behavioural mechanism supporting friendships and alliances6, and neural activity maintained a running account of these social investments. Confronted with an aggressive intruder, behavioural and neural population responses reflected empathy and were buffered by the presence of a partner. Our findings reveal a highly distributed neurophysiological ledger of social dynamics, a potential computational foundation supporting communal life in primate societies, including our own.

Interpersonal heart rate synchrony predicts effective information processing in a naturalistic group decision-making task.

Groups often outperform individuals in problem-solving. Nevertheless, failure to critically evaluate ideas risks suboptimal outcomes through so-called groupthink. Prior studies have shown that people who hold shared goals, perspectives, or understanding of the environment show similar patterns of brain activity, which itself can be enhanced by consensus-building discussions. Whether shared arousal alone can predict collective decision-making outcomes, however, remains unknown. To address this gap, we computed interpersonal heart rate synchrony, a peripheral index of shared arousal associated with joint attention, empathic accuracy, and group cohesion, in 44 groups (n = 204) performing a collective decision-making task. The task required critical examination of all available information to override inferior, default options and make the right choice. Using multidimensional recurrence quantification analysis (MdRQA) and machine learning, we found that heart rate synchrony predicted the probability of groups reaching the correct consensus decision with >70% cross-validation accuracy-significantly higher than that predicted by the duration of discussions, subjective assessment of team function or baseline heart rates alone. We propose that heart rate synchrony during group discussion provides a biomarker of interpersonal engagement that facilitates adaptive learning and effective information sharing during collective decision-making.

Within-individual changes reveal increasing social selectivity with age in rhesus macaques.

Accumulating evidence in humans and other mammals suggests older individuals tend to have smaller social networks. Uncovering the cause of these declines can inform how changes in social relationships with age affect health and fitness in later life. While age-based declines in social networks have been thought to be detrimental, physical and physiological limitations associated with age may lead older individuals to adjust their social behavior and be more selective in partner choice. Greater selectivity with age has been shown in humans, but the extent to which this phenomenon occurs across the animal kingdom remains an open question. Using longitudinal data from a population of rhesus macaques on Cayo Santiago, we provide compelling evidence in a nonhuman animal for within-individual increases in social selectivity with age. Our analyses revealed that adult female macaques actively reduced the size of their networks as they aged and focused on partners previously linked to fitness benefits, including kin and partners to whom they were strongly and consistently connected earlier in life. Females spent similar amounts of time socializing as they aged, suggesting that network shrinkage does not result from lack of motivation or ability to engage, nor was this narrowing driven by the deaths of social partners. Furthermore, females remained attractive companions and were not isolated by withdrawal of social partners. Taken together, our results provide rare empirical evidence for social selectivity in nonhumans, suggesting that patterns of increasing selectivity with age may be deeply rooted in primate evolution.

Natural disaster and immunological aging in a nonhuman primate.

Weather-related disasters are increasing in frequency and severity, leaving survivors to cope with ensuing mental, financial, and physical hardships. This adversity can exacerbate existing morbidities, trigger new ones, and increase the risk of mortality-features that are also characteristic of advanced age-inviting the hypothesis that extreme weather events may accelerate aging. To test this idea, we examined the impact of Hurricane Maria and its aftermath on immune cell gene expression in large, age-matched, cross-sectional samples from free-ranging rhesus macaques (Macaca mulatta) living on an isolated island. A cross section of macaques was sampled 1 to 4 y before (n = 435) and 1 y after (n = 108) the hurricane. Hurricane Maria was significantly associated with differential expression of 4% of immune-cell-expressed genes, and these effects were correlated with age-associated alterations in gene expression. We further found that individuals exposed to the hurricane had a gene expression profile that was, on average, 1.96 y older than individuals that were not-roughly equivalent to an increase in 7 to 8 y of a human life. Living through an intense hurricane and its aftermath was associated with expression of key immune genes, dysregulated proteostasis networks, and greater expression of inflammatory immune cell-specific marker genes. Together, our findings illuminate potential mechanisms through which the adversity unleashed by extreme weather and potentially other natural disasters might become biologically embedded, accelerate age-related molecular immune phenotypes, and ultimately contribute to earlier onset of disease and death.

Attention deficits linked with proclivity to explore while foraging.

All mobile organisms forage for resources, choosing how and when to search for new opportunities by comparing current returns with the average for the environment. In humans, nomadic lifestyles favouring exploration have been associated with genetic mutations implicated in attention deficit hyperactivity disorder (ADHD), inviting the hypothesis that this condition may impact foraging decisions in the general population. Here we tested this pre-registered hypothesis by examining how human participants collected resources in an online foraging task. On every trial, participants chose either to continue to collect rewards from a depleting patch of resources or to replenish the patch. Participants also completed a well-validated ADHD self-report screening assessment at the end of sessions. Participants departed resource patches sooner when travel times between patches were shorter than when they were longer, as predicted by optimal foraging theory. Participants whose scores on the ADHD scale crossed the threshold for a positive screen departed patches significantly sooner than participants who did not meet this criterion. Participants meeting this threshold for ADHD also achieved higher reward rates than individuals who did not. Our findings suggest that ADHD attributes may confer foraging advantages in some environments and invite the possibility that this condition may reflect an adaptation favouring exploration over exploitation.

The Brain Economy: Advancing Brain Science to Better Understand the Modern Economy.

The coming years are likely to be turbulent due to a myriad of factors or polycrisis, including an escalation in climate extremes, emerging public health threats, weak productivity, increases in global economic instability and further weakening in the integrity of global democracy. These formidable challenges are not exogenous to the economy but are in some cases generated by the system itself. They can be overcome, but only with far-reaching changes to global economics. Our current socio-economic paradigm is insufficient for addressing these complex challenges, let alone sustaining human development, well-being and happiness. To support the flourishing of the global population in the age of polycrisis, we need a novel, person-centred and collective paradigm. The brain economy leverages insights from neuroscience to provide a novel way of centralising the human contribution to the economy, how the economy in turn shapes our lives and positive feedbacks between the two. The brain economy is primarily based on Brain Capital, an economic asset integrating brain health and brain skills, the social, emotional, and the diversity of cognitive brain resources of individuals and communities. People with healthy brains are essential to navigate increasingly complex systems. Policies and investments that improve brain health and hence citizens' cognitive functions and boost brain performance can increase productivity, stimulate greater creativity and economic dynamism, utilise often underdeveloped intellectual resources, afford social cohesion, and create a more resilient, adaptable and sustainability-engaged population.

Clinical Outcome Data of Children Treated with Cannabis-Based Medicinal Products for Treatment Resistant Epilepsy-Analysis from the UK Medical Cannabis Registry.

BACKGROUND: There is a paucity of high-quality evidence of the efficacy and safety of cannabis-based medicinal products in treatment of treatment-resistant epilepsy (TRE) in children. METHODS: A case series of children (<18 years old) with TRE from the UK Medical Cannabis Registry was analyzed. Primary outcomes were ≥50% reduction in seizure frequency, changes in the Impact of Pediatric Epilepsy Score (IPES), and incidence of adverse events. RESULTS: Thirty-five patients were included in the analysis. Patients were prescribed during their treatment with the following: CBD isolate oils (n = 19), CBD broad-spectrum oils (n = 17), and CBD/Δ9-THC combination therapy (n = 17). Twenty-three (65.7%) patients achieved a ≥50% reduction in seizure frequency. 94.1% (n = 16) of patients treated with CBD and Δ9-THC observed a ≥50% reduction in seizure frequency compared to 31.6% (n = 6) and 17.6% (n = 3) of patients treated with CBD isolates and broad-spectrum CBD products, respectively (p< 0.001). Twenty-six (74.3%) adverse events were reported by 16 patients (45.7%). The majority of these were mild (n = 12; 34.2%) and moderate (n = 10; 28.6%). CONCLUSION: The results of this study demonstrate a positive signal of improved seizure frequency in children treated with Cannabis-based medicinal products (CBMPs) for TRE. Moreover, the results suggest that CBMPs are well-tolerated in the short term. The limitations mean causation cannot be determined in this open-label, case series.

Resilience of primal world beliefs to the initial shock of the COVID-19 pandemic.

INTRODUCTION: People hold general beliefs about the world called primals (e.g., the world is Safe, Intentional), which are strongly linked to individual differences in personality, behavior, and mental health. How such beliefs form or change across the lifespan is largely unknown, although theory suggests that beliefs become more negative after disruptive events. The COVID-19 pandemic provided an opportunity to test whether dramatic world changes and personal adversity affect beliefs. METHOD: In a longitudinal, quasi-experimental, pre-registered design, 529 US participants (51% female, 76% White) provided ratings of primals before and several months after pandemic onset, and information about personal adversity (e.g., losing family, financial hardship). Data were compared to 398 participants without experience of the pandemic. RESULTS: The average person in our sample showed no change in 23 of the 26 primals, including Safe, in response to the early pandemic, and only saw the world as slightly less Alive, Interactive, and Acceptable. Higher adversity, however, was associated with slight declines in some beliefs. One limitation is that participants were exclusively American. CONCLUSION: Primals were remarkably stable during the initial shock wrought by a once-in-a-century pandemic, supporting a view of primals as stable lenses through which people interpret the world.

Decomposing loss aversion from gaze allocation and pupil dilation.

Loss-averse decisions, in which one avoids losses at the expense of gains, are highly prevalent. However, the underlying mechanisms remain controversial. The prevailing account highlights a valuation bias that overweighs losses relative to gains, but an alternative view stresses a response bias to avoid choices involving potential losses. Here we couple a computational process model with eye-tracking and pupillometry to develop a physiologically grounded framework for the decision process leading to accepting or rejecting gambles with equal odds of winning and losing money. Overall, loss-averse decisions were accompanied by preferential gaze toward losses and increased pupil dilation for accepting gambles. Using our model, we found gaze allocation selectively indexed valuation bias, and pupil dilation selectively indexed response bias. Finally, we demonstrate that our computational model and physiological biomarkers can identify distinct types of loss-averse decision makers who would otherwise be indistinguishable using conventional approaches. Our study provides an integrative framework for the cognitive processes that drive loss-averse decisions and highlights the biological heterogeneity of loss aversion across individuals.

Neuronal Activity in the Posterior Cingulate Cortex Signals Environmental Information and Predicts Behavioral Variability during Trapline Foraging.

Animals engage in routine behavior 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 deviate from routines remain unexplored. To investigate the representation of environmental information during routine foraging, we recorded the activity of single neurons in posterior cingulate cortex (PCC) in 2 male 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 deviate 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 may mediate the influence of information on variability in choice behavior.SIGNIFICANCE STATEMENT Many animals seek information to better guide their decisions and update behavioral routines. In our study, subjects visually searched through a set of targets on every trial to gather two rewards. Greater amounts of information about the distribution of rewards predicted less variability in choice patterns, whereas smaller amounts predicted greater variability. We recorded from the posterior cingulate cortex, an area implicated in the coding of reward and uncertainty, and discovered that these neurons signaled the expected information about the distribution of rewards instead of signaling expected rewards. The activity in these cells also predicted the amount of variability in choice behavior. These findings suggest that the posterior cingulate helps direct the search for information to augment routines.

Relative numerical middle in rhesus monkeys.

Animals show vast numerical competence in tasks that require both ordinal and cardinal numerical representations, but few studies have addressed whether animals can identify the numerical middle in a sequence. Two rhesus monkeys (Macaca mulatta) learned to select the middle dot in a horizontal sequence of three dots on a touchscreen. When subsequently presented with longer sequences composed of 5, 7 or 9 items, monkeys transferred the middle rule. Accuracy decreased as the length of the sequence increased. In a second test, we presented monkeys with asymmetrical sequences composed of nine items, where the numerical and spatial middle were distinct and both monkeys selected the numerical middle over the spatial middle. Our results demonstrate that rhesus macaques can extract an abstract numerical rule to bisect a discrete set of items.

Association of vaping with decreased vascular endothelial growth factor expression and decreased microvessel density in cutaneous wound healing tissue in rats.

Vaping is suggested to be a risk factor for poor wound healing akin to smoking. However, the molecular and histologic mechanisms underlying this postulation remain unknown. Our study sought to compare molecular and histologic changes in cutaneous flap and non-flap tissue between vaping, smoking and control cohorts. Animal study of 15 male Sprague-Dawley rats was randomized to three cohorts: negative control (n = 5), e-cigarette (n = 5) and cigarette (n = 5) and exposed to their respective treatments with serum cotinine monitoring. After 30 days, random pattern flaps were raised and healed for 2 weeks after which skin punch biopsies of flap and non-flap tissues were collected for quantitative-reverse transcription-polymerase chain reaction of three selected wound healing genes (transforming growth factor ß [TGF-ß], vascular endothelial growth factor [VEGF], matrix metalloproteinase-1 [MMP-1]); then, immunohistochemistry for CD68 expression, α-smooth muscle actin looking at microvessel density (MVD) and in situ hybridization to localize VEGF production were undertaken. In flap tissue, vaping (mean[SEM]) (0.61[0.07]) and smoking (0.70[0.04]) were associated with decreased fold change of VEGF expression compared with controls (0.91[0.03]) (p < 0.05, p < 0.05, respectively). In non-flap tissue, only vaping was associated with decreased VEGF expression (mean[SEM]) (0.81[0.07]), compared with controls (1.17[0.10]) (p < 0.05) with expression primarily localized to basal keratinocytes and dermal capillaries. Immunohistochemistry showed decreased MVD in smoking (0.27[0.06]) and vaping (0.26[0.04]) flap tissue compared to matched controls (0.65[0.14]) (p < 0.05, p < 0.05, respectively) and decreased areas of fibrosis compared with controls on gross histology. Vaping and smoking were similarly associated with decreased VEGF expression, MVD and fibrotic changes in flap tissue. The results suggest attenuated angiogenesis via decreased VEGF expression as a mechanism for poor wound healing in vaping-exposed rats.

Latent goal models for dynamic strategic interaction.

Understanding the principles by which agents interact with both complex environments and each other is a key goal of decision neuroscience. However, most previous studies have used experimental paradigms in which choices are discrete (and few), play is static, and optimal solutions are known. Yet in natural environments, interactions between agents typically involve continuous action spaces, ongoing dynamics, and no known optimal solution. Here, we seek to bridge this divide by using a "penalty shot" task in which pairs of monkeys competed against each other in a competitive, real-time video game. We modeled monkeys' strategies as driven by stochastically evolving goals, onscreen positions that served as set points for a control model that produced observed joystick movements. We fit this goal-based dynamical system model using approximate Bayesian inference methods, using neural networks to parameterize players' goals as a dynamic mixture of Gaussian components. Our model is conceptually simple, constructed of interpretable components, and capable of generating synthetic data that capture the complexity of real player dynamics. We further characterized players' strategies using the number of change points on each trial. We found that this complexity varied more across sessions than within sessions, and that more complex strategies benefited offensive players but not defensive players. Together, our experimental paradigm and model offer a powerful combination of tools for the study of realistic social dynamics in the laboratory setting.

Extranasal Manifestations of Allergy in the Head and Neck.

PURPOSE OF REVIEW: Allergic rhinitis and allergic asthma are well-described disease entities with broad exposure in clinical and research allergy forums. Associations between allergic inflammation and upper airway diseases of chronic laryngitis, otitis media, obstructive sleep apnea, and oral allergy syndrome are less well understood and described in the literature. RECENT FINDINGS: This review discusses the relationship between atopy and diseases of the upper airway, oral cavity, larynx, and ear. The similar respiratory mucosal lining the upper aerodigestive tract, with sensitized mast cells and inflammatory mediators in the submucosa, results in a variety of extranasal manifestations of allergic diseases in the head and neck which are less well characterized. Associations between allergic inflammation and upper airway diseases of chronic laryngitis, otitis media, obstructive sleep apnea, and oral allergy syndrome are less well understood and described in the literature. This review will summarize the relevant pathophysiology and symptomology, association with allergic sensitization, and clinical considerations of these disorders.

Quality improvement in tracheostomy care: A multidisciplinary approach to standardizing tracheostomy care to reduce complications.

PURPOSE: Develop a model for quality improvement in tracheostomy care and decrease tracheostomy-related complications. METHODS: This study was a prospective quality improvement project at an academic tertiary care hospital. A multidisciplinary team was assembled to create institutional guidelines for clinical care during the pre-operative, intra-operative, and post-operative periods. Baseline data was compiled by retrospective chart review of 160 patients, and prospective tracking of select points over 8 months in 73 patients allowed for analysis of complications and clinical parameters. RESULTS: Implementation of a quality improvement team was successful in creating guidelines, setting baseline parameters, and tracking data with run charts. Comparison of pre- and post-guideline data showed a trend toward decreased rate of major complications from 4.38% to 2.74% (p = 0.096). Variables including time to tracheotomy for prolonged intubation, surgical technique, day of first tracheostomy tube change, and specialty performing surgery did not show increased risk of complications. There were increased tracheostomy-related complications in cold months (p = 0.04). CONCLUSIONS: An interdisciplinary quality improvement team can improve tracheostomy care by identifying system factors, standardizing care among specialties, and providing continuous monitoring of select data points.

The population genomics of rhesus macaques (Macaca mulatta) based on whole-genome sequences.

Rhesus macaques (Macaca mulatta) are the most widely used nonhuman primate in biomedical research, have the largest natural geographic distribution of any nonhuman primate, and have been the focus of much evolutionary and behavioral investigation. Consequently, rhesus macaques are one of the most thoroughly studied nonhuman primate species. However, little is known about genome-wide genetic variation in this species. A detailed understanding of extant genomic variation among rhesus macaques has implications for the use of this species as a model for studies of human health and disease, as well as for evolutionary population genomics. Whole-genome sequencing analysis of 133 rhesus macaques revealed more than 43.7 million single-nucleotide variants, including thousands predicted to alter protein sequences, transcript splicing, and transcription factor binding sites. Rhesus macaques exhibit 2.5-fold higher overall nucleotide diversity and slightly elevated putative functional variation compared with humans. This functional variation in macaques provides opportunities for analyses of coding and noncoding variation, and its cellular consequences. Despite modestly higher levels of nonsynonymous variation in the macaques, the estimated distribution of fitness effects and the ratio of nonsynonymous to synonymous variants suggest that purifying selection has had stronger effects in rhesus macaques than in humans. Demographic reconstructions indicate this species has experienced a consistently large but fluctuating population size. Overall, the results presented here provide new insights into the population genomics of nonhuman primates and expand genomic information directly relevant to primate models of human disease.

Deconstructing sociality: the types of social connections that predict longevity in a group-living primate.

Many species use social interactions to cope with challenges in their environment and a growing number of studies show that individuals which are well-connected to their group have higher fitness than socially isolated individuals. However, there are many ways to be 'well-connected' and it is unclear which aspects of sociality drive fitness benefits. Being well-connected can be conceptualized in four main ways: individuals can be socially integrated by engaging in a high rate of social behaviour or having many partners; they can have strong and stable connections to favoured partners; they can indirectly connect to the broader group structure; or directly engage in a high rate of beneficial behaviours, such as grooming. In this study, we use survival models and long-term data in adult female rhesus macaques (Macaca mulatta) to compare the fitness outcomes of multiple measures of social connectedness. Females that maintained strong connections to favoured partners had the highest relative survival probability, as did females well-integrated owing to forming many weak connections. We found no survival benefits to being structurally well-connected or engaging in high rates of grooming. Being well-connected to favoured partners could provide fitness benefits by, for example, increasing the efficacy of coordinated or mutualistic behaviours.

Indulgent Foods Can Paradoxically Promote Disciplined Dietary Choices.

As obesity rates continue to rise, interventions promoting healthful choices will become increasingly important. Here, participants ( N = 79) made binary choices between familiar foods; some trials contained a common consequence that had a constant probability of receipt regardless of the participant's choice. We theorized-on the basis of simulations using a value-normalization model-that indulgent common consequences potentiated disciplined choices by shaping other options' perceived healthfulness and tastiness. Our experimental results confirmed these predictions: An indulgent common consequence more than doubled the rate of disciplined choices. We used eye-gaze data to provide insights into the underlying mechanisms, finding that an indulgent common consequence biased eye gaze toward healthful foods. Furthermore, attention toward the common consequence predicted individual differences in behavioral bias. Results were replicated across two independent samples receiving distinct goal primes. These results demonstrate that introducing an irrelevant indulgent food can alter processing of healthier items-and thus promote disciplined choices.