The macaque genus includes 25 species with diverse social systems, ranging from low to high social tolerance grades. Such interspecific behavioral variability provides a unique model to tackle the evolutionary foundation of primate social brain. Yet, the neuroanatomical correlates of these social tolerance grades remain unknown. To address this question, we expressed social tolerance grades within a novel cognitive framework and analyzed post-mortem structural scans from 12 macaque species. Our results show that amygdala volume is a subcortical predictor of macaques’ social tolerance, with high tolerance species exhibiting larger amygdala than low tolerance ones. We further investigated the developmental trajectory of amygdala across social grades and found that intolerant species showed a gradual increase in relative amygdala volume across the lifespan. Unexpectedly, tolerant species exhibited a decrease in relative amygdala volume across the lifespan, contrasting with the age-related increase observed in intolerant species—a developmental pattern previously undescribed in primates. Taken together, these findings provide valuable insights into the cognitive, neuroanatomical, and evolutionary basis of primates’ social behaviors.
eLife digest
Macaque monkeys live under a variety of social regimes. Some species flourish within highly structured, hierarchical societies, while others navigate more tolerant yet less predictable social networks. Primatologists have categorised these social differences, including how often reconciliation occurs after conflicts, into four levels of social tolerance. However, the neuronal mechanisms underlying these social variations remain poorly understood.
Closely related species offer a natural laboratory for studying the social brain in primates. To investigate how neural networks may have evolved in response to differing social challenges, Silvère et al. analysed 43 brain scans from 12 macaque species. All data were gathered from animals that had died of natural or accidental causes
The scans showed that the relative size of a species’ amygdala – a brain region involved in emotional responses, decision-making, and memory – correlates with its level of social tolerance. For example, low-tolerance species are born with a smaller amygdala, which grows larger with age. Conversely, in more socially tolerant species, the amygdala decreases in size as they age, contrasting with findings in other primates, including humans.
These findings imply that living in a more tolerant social environment could impose greater cognitive demands on the brain, with the amygdala possibly playing a part in complex social cognition. In contrast, the volume of a brain region called the hippocampus revealed more variable differences across social grades among macaques, with a more significant effect observed only in individuals aged between 13 and 18 years. Additionally, differences in hippocampal volume also varied among monkeys living in different areas, supporting the idea that certain regions contribute to social cognitive processes in tolerant species, particularly during developmental phases linked to social maturation.
Exploring natural variation in brain evolution and function opens new avenues for primate neuroscience. A more extensive comparative analysis across all living primate species could further clarify evolutionary pathways. Moreover, identifying neural networks that are either evolutionarily conserved or highly variable may help shape new research directions aimed at understanding the biological basis of neurodivergence.
tonkean macaquesfascicularis macaquesother macaque speciesResearch organismRhesus macaqueOtherhttps://ror.org/00rbzpz17Agence Nationale de la RechercheANR-21-CE37-0016SalletJeromeBallestaSebastienhttps://ror.org/029chgv08Wellcome Trust10.35802/203139SalletJeromeFrench State RegionCPER I2MT 2014-2021LamyJulienPoChrystelleFrench State RegionR-IRM (2021-2027)LamyJulienPoChrystellehttps://ror.org/019w4f821European UnionEuropean Regional Development Fund “FEDER Grand Est”LamyJulienPoChrystelleThe funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. For the purpose of Open Access, the authors have applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission.Author impact statementMacaque’s social tolerance grades, through its underlying cognitive demands, shape subcortical structures volumes.publishing-routeprcIntroduction
A complex social environment implies a greater cognitive demand of social representations and interactions, which is one of the driving forces behind the evolution of the primate brain (Dunbar, 2009; Freeberg et al., 2012; Heldstab et al., 2022). Correlations between social environment and variations in brain structure volumes have been reported, both in humans (Kanai et al., 2012; Maguire et al., 2000; Parkinson et al., 2017) and in non-human primates (NHP; Noonan et al., 2014; Sallet et al., 2011; Meguerditchian et al., 2021; Testard et al., 2022). In rhesus macaques (Macaca mulatta), previous studies have demonstrated that interindividual variation in social characteristics—such as hierarchical status (Noonan et al., 2014) or group size (Sallet et al., 2011; Testard et al., 2022) – is associated with grey matter volume in core regions of the social brain, including the amygdala, the hippocampus, the superior temporal sulcus (STS), and the rostral prefrontal cortex (rPFC). Supporting the broader relevance of these findings across Cercopithecinae, a study in olive baboons (Papio anubis) revealed that individuals living in larger social groups exhibited greater total brain volumes, with an effect primarily driven by white matter (Meguerditchian et al., 2021).
Despite the existence of 25 species within the Macaca genus (Cooper et al., 2022; Cords, 2012; Ghosh et al., 2022; Thierry, 2007; Thierry et al., 2004), most neuroscience research focuses on two species, M. mulatta and Macaca fascicularis (and in rare cases Macaca nemestrina and Macaca fuscataCarlo et al., 2010; Isa et al., 2009; Maranesi et al., 2014). In spite of the relatively short evolutionary divergence time within this genus (6–8 million years Perelman et al., 2011), the various macaque species display a considerable interspecific variety of social behaviors while usually maintaining a multi-male, multi-female, and multi-generational social structure (Balasubramaniam et al., 2018; Thierry, 2007; Thierry and Sapolsky, 2000). These behavioral differences are characterized by different styles of dominance (Balasubramaniam et al., 2012), severity of agonistic interactions (Duboscq et al., 2014), nepotism (Thierry and Berman, 2010; Duboscq et al., 2013; Sueur et al., 2011), and submission signals (de Waal and Luttrell, 1985; Rincon et al., 2023), among the 18 covariant behavioral traits described in Thierry’s classification of social tolerance (Thierry, 2021; Thierry, 2017; Thierry and Sapolsky, 2000).
Despite this large behavioral variability, macaque species display broadly similar general cognitive abilities (Aguenounon et al., 2022). Specific differences observed in domains such as inhibitory control or social flexibility are thus more likely to reflect adaptive responses to species-specific social constraints, rather than intrinsic disparities in overall intelligence (Joly et al., 2017; Loyant et al., 2023). Altogether, the socio-behavioral diversity within the Macaca genus provides a compelling model to investigate how social ecology shapes cognition and its neural substrates.
The concept of social tolerance, central to this comparative approach, has sometimes been used in a vague or unidimensional way. As Thierry, 2021 pointed out, the notion was initially constructed around variations in agonistic relationships – dominance, aggressiveness, appeasement, or reconciliation behaviors – before being expanded to include affiliative behaviors, allomaternal care, or male–male interactions (Thierry, 2021). These traits do not necessarily align along a single hierarchical axis but rather reflect a multidimensional complexity of social style, in which each trait may have co-evolved with others (Thierry, 2021; Thierry and Sapolsky, 2000; Thierry et al., 2004). Moreover, the lack of a standardized scientific definition has sometimes led to labeling species as ‘tolerant’ or ‘intolerant’ without explicit criteria (Gumert and Ho, 2008; Patzelt et al., 2014).
To ground the investigation of social tolerance in a comparative neuroanatomical framework, we introduced a tentative working model that articulates behavioral traits, cognitive dimensions, and their potential subcortical neural substrates. Drawing upon 18 behavioral traits identified in Thierry’s comparative analyses (Thierry, 2021; Thierry, 2007), we organized these traits into three core dimensions: socio-cognitive demands, behavioral inhibition, and the predictability of the social environment (Table 1). This conceptualization did not aim to redefine social tolerance itself, but rather to provide a structured basis for testing neuroanatomical hypotheses related to the volume of relevant subcortical areas and social style variability. It echoes recent efforts to bridge behavioral ecology and cognitive neuroscience by linking specific mental abilities – such as executive functions or metacognition – with distinct prefrontal regions shaped by social and ecological pressures (Bouret et al., 2024; Testard et al., 2022).
Cognitive and neuroanatomical categorization of behavioral traits associated with macaque social tolerance.
Social trait
Underlying social consequences
Cognitive dimension
Neural correlate
Complexity of communication system
Demands in interpreting social signals and adjusting communication to context (Liebal et al., 2014).
Higher socio-cognitive demands
Amygdala volume higher (Bickart et al., 2011; Sallet et al., 2011); Hippocampus volume higher (Kanai et al., 2012; Todorov et al., 2019)9,10
Rate of reconciliation
Demands in recalling social history and regulating affiliation (Thierry and Sapolsky, 2000).
Male-to-male coalitions
Demands in social knowledge and strategic social decisions (Petit et al., 1997; Silk, 1999).
Cooperative behaviors
Demands in understanding intentions and coordinating actions during interactions (Demaria and Thierry, 2001; Micheletta et al., 2012).
Intensity of aggression
Demands in inhibiting impulsive behaviors and regulating emotions (Adams et al., 2015; Loyant et al., 2023).
Better inhibitory control
Amygdala volume lower (Tottenham et al., 2010); Hippocampus volume unchanged (Tottenham et al., 2010).
Confidence of social play
Demands in adjusting behavior and inhibiting responses in mutual interactions (Petit et al., 2008; Scopa and Palagi, 2016).
Resource distribution evenness
Demands in adjusting behavior during competitive interactions and regulating emotions (Thierry, 2007).
Kin bias (nepotism)
Kin knowledge is less informative to predict social relationships (Silk, 2002; Silk et al., 2003).
Lower predictability of social environment (heightened chronic stress)
Amygdala volume higher (Bickart et al., 2014; Sallet et al., 2011; Tottenham et al., 2010); Hippocampus volume lower (Kim et al., 2015; Lyons et al., 2001; Meyer and Hamel, 2014).
Dominance asymmetry
Conflicts are not always won by dominants, leading to greater outcome unpredictability (de Vries et al., 2006; Thierry, 2007).
Formal submission signals
Communication during conflict is less predictive of outcomes (Flack et al., 2006; Waller et al., 2013).
Intensity of female rank inheritance
Matrilinear knowledge is less informative to predict social relationships (Hill and Okayasu, 1995; Kutsukake, 2000).
Rate of affiliative contact
Affiliative networks are denser, reducing predictability (Duboscq et al., 2013; Massen et al., 2010; Silk et al., 2003).
Rate of counter-aggression
Subordinates are more likely to retaliate, making social outcomes less predictable (Balasubramaniam et al., 2012; Petit et al., 1997).
Rate of immature interference in mating
Mounting behaviour increases social interactions, producing more erratic social patterns (Petit et al., 2008).
Centrality of top-ranking males
Low centrality of top-ranking males decreased social network predictability (Sueur et al., 2011).
Mother protectiveness
Limits how much infants interact with other group members (Maestripieri, 1994).
Unclassified
/
Allomothering behavior
Reciprocal benefits for females and infants (Fairbanks, 1990).
Delayed male dispersal
Limits the range of social networks open to individuals (Thierry, 2007).
Navigating social life in primate societies requires substantial cognitive resources: individuals must not only track multiple relationships, but also regulate their own behavior, anticipate others’ reactions, and adapt flexibly to changing social contexts. Taking advantage of databases of magnetic resonance imaging (MRI) structural scans, we conducted the first comparative study integrating neuroanatomical data and social behavioral data from closely related primate species of the same genus to address the following questions: To what extent can differences in volumes of subcortical brain structures be correlated with varying degrees of social tolerance? Additionally, we explored whether these dispositions reflect primarily innate features, shaped by evolutionary processes, or acquired through socialization within more or less tolerant social environments.
The first category, socio-cognitive demands, refers to the cognitive resources needed to process, monitor, and flexibly adapt to complex social environments. Linking those parameters to neurological data is at the core of the social brain theory (Dunbar, 2009). Macaques’ social systems require advanced abilities in social memory, perspective-taking, and partner evaluation (Freeberg et al., 2012). This is particularly true in tolerant species, where the increased frequency and diversity of interactions may amplify the demands on cognitive tracking and flexibility. Tolerant macaque species typically live in larger groups with high interaction frequencies, low nepotism, and a wider range of affiliative and cooperative behaviors, including reconciliation, coalition-building, and signal flexibility (Thierry, 2021; Thierry and Sapolsky, 2000). Tolerant macaque species also exhibit a more diverse and flexible vocal and facial repertoire than intolerant ones, which may help reduce ambiguity and facilitate coordination in dense social networks (Rincon et al., 2023; Scopa and Palagi, 2016; Rebout et al., 2020). Experimental studies further show that macaques can use facial expressions to anticipate the likely outcomes of social interactions, suggesting a predictive function of facial signals in managing uncertainty (Micheletta et al., 2012; Waller et al., 2016). Even within less tolerant species, like M. mulatta, individual variation in facial expressivity has been linked to increased centrality in social networks and greater group cohesion, pointing to the adaptive value of expressive signaling across social styles (Whitehouse et al., 2024).
The second category, inhibitory control, includes traits that involve regulating impulsivity, aggression, or inappropriate responses during social interactions. Tolerant macaques have been shown to perform better in tasks requiring behavioral inhibition and also express lower aggression and emotional reactivity than intolerant macaques both in experimental and in natural contexts (Joly et al., 2017; Loyant et al., 2023). These features point to stronger self-regulation capacities in species with egalitarian or less rigid hierarchies. More broadly, inhibition – especially in its strategic form (self-control) – has been proposed to play a key role in the cohesion of stable social groups. Comparative analyses across mammals suggest that this capacity has evolved primarily in anthropoid primates, where social bonds require individuals to suppress immediate impulses in favor of longer-term group stability (Dunbar and Shultz, 2025). This view echoes the conjecture of Passingham et al., 2012, who proposed that the expansion of lateral prefrontal area BA10 in anthropoids enabled the kind of behavioral flexibility needed to navigate complex social environments (Passingham et al., 2012).
The third category, social environment predictability, reflects how structured and foreseeable social interactions are within a given society. In tolerant species, social interactions are more fluid and less kin-biased, leading to greater contextual variation and role flexibility, which likely imply a sustained level of social awareness. In fact, as suggested by recent research, such social uncertainty and prolonged incentives are reflected by stress-related physiology: tolerant macaques such as M. tonkeana display higher basal cortisol levels, which may be indicative of a chronic mobilization of attentional and regulatory resources to navigate less predictable social environments (Sadoughi et al., 2021).
Each behavioral trait was individually evaluated based on existing empirical literature regarding the types of cognitive operations it likely involves. When a primary cognitive dimension could be identified, the trait was assigned accordingly. However, some behaviors – such as maternal protection, allomaternal care, or delayed male dispersal – do not map neatly onto a single cognitive process. These traits likely emerge from complex configurations of affective and social-motivational systems and may be better understood through frameworks such as attachment theory (Suomi, 2008), which emphasizes the integration of social bonding, emotional regulation, and contextual plasticity. While these dimensions fall beyond the scope of the present framework, they offer promising directions for future research, particularly in relation to the hypothalamic and limbic substrates of social and reproductive behavior.
Rather than forcing these traits into potentially misleading categories, we chose to leave them unclassified within our current cognitive framework. This decision reflects both a commitment to conceptual clarity and the recognition that some behaviors emerge from a convergence of cognitive demands that cannot be neatly isolated. This tripartite framework, leaving aside reproductive-related traits, provides a structured lens through which to link behavioral diversity to specific cognitive processes and generate neuroanatomical predictions.
We therefore associated these three categories with neuroanatomical hypotheses regarding variations in the volume of two subcortical structures of interest, the amygdala and the hippocampus. Based on existing literature on the effects of the socio-cognitive demands, inhibitory control, and social unpredictability – particularly when it induces sustained activation of stress-related systems – on the volume of these two regions (Bickart et al., 2011; Caetano et al., 2021; Coplan et al., 2014; Haley et al., 2012; Howell et al., 2014; Lyons et al., 2001; Sallet et al., 2011), we hypothesized that increased cognitive demands from the social environment could lead to a differential effect on amygdala and hippocampus volumes (Bickart et al., 2011; Haley et al., 2012; Lyons et al., 2001; Sallet et al., 2011). We summarized our working hypotheses into a table comparing grade 4 and grade 1 species (Table 1).
This table summarizes the 18 behavioral traits used to characterize social tolerance grades in the Macaca genus, based on Thierry’s comparative framework. Each trait is associated with a description of its underlying cognitive implications and assigned—when applicable—to one of three cognitive dimensions: (i) socio-cognitive demands (e.g. tracking partners, coordinating actions), (ii) behavioral inhibition (e.g. regulating impulsivity), or (iii) predictability of the social environment (e.g. anticipating interaction outcomes). The final column presents the hypothesized effects of these dimensions on the volume of two subcortical structures: the amygdala and the hippocampus. Traits that could not be clearly assigned to a specific cognitive dimension—often related to maternal or reproductive strategies—are marked as ‘unclassified’. This framework is used to generate testable predictions about the neural substrates of social style diversity in macaques.
We tested our hypothesis using 42 post-mortem MRI acquisitions of 12 macaque species representing the four grades of social tolerance. The dataset was both composed of samples from open access databases (Milham et al., 2018; Navarrete et al., 2018; Sakai et al., 2018) as well as newly and unpublished samples from the collection of the Centre de Primatologie de l’Université de Strasbourg (CdP) and INSERM-Oxford University. These samples include brain images of Macaca tonkeana and Macaca thibetana, two macaque species that have never been scanned before as well as a scan of Macaca nigra that is rare in the existing literature (Navarrete et al., 2018; Sakai et al., 2023). Up to this date, only one study has included tolerant species of macaque monkeys in such neuroanatomical comparative framework (Jones et al., 2021). While Jones et al., 2021 identified interspecific differences in amygdala microstructure and serotonergic innervation, their histological approach did not assess structural volumes at the whole-brain level. To our knowledge, our study is the first to report neuroanatomical correlates of social tolerance grades of the Macaca genus based on post-mortem MRI volumetric analysis. This approach reveals two key findings. First, across species, amygdala volume is positively correlated with social tolerance grades, with more tolerant macaque species exhibiting larger amygdala volumes. Second, developmental trajectories of the amygdala diverge according to social style: in intolerant species, amygdala volume increases with age – as commonly reported in the literature (Schumann et al., 2019) – whereas in tolerant species, we observe an unexpected marked decrease over the lifespan. This study offers a novel and valuable perspective by comparing interspecies brain structures to investigate the functioning of the social brain, while accounting for key socio-cognitive variables.
Results
We obtained structural MRI scans of 42 macaques of 12 macaque species. Using a semi-automated registration to an atlas (SARM, Hartig et al., 2021), we extracted amygdala and hippocampus volumes and analyzed whether these covaried with social grade and age, using a Bayesian model. The raw relations between the main response variables (the amygdala’s and hippocampus volumes) are depicted in Figure 1.
Model predictors of the amygdala and hippocampus, and volume predictions across social tolerance grades.
First row (A–D): Model predictors and responses for amygdala volume. The volume ratio is calculated as the amygdala volume divided by the total brain volume (excluding the myelencephalon and cerebellum). (A) Distribution of amygdala volume ratios across social tolerance grades. (B) Distribution of amygdala volume ratios by sex. (C) Distribution of amygdala volume ratios by husbandry condition (enclosed vs. semi-free). (D) Distribution of amygdala volume ratios by the frozen status. (E) Distribution of amygdala volume ratios by age. Second row (F–J): Model predictors and responses for hippocampal volume. The volume ratio is calculated as the hippocampal volume divided by the total brain volume (excluding the myelencephalon and cerebellum). (F) Distribution of hippocampal volume ratios across social tolerance grades. (G) Distribution of hippocampal volume ratios by sex. (H) Distribution of hippocampal volume ratios by husbandry condition (enclosed vs. semi-free). (I) Distribution of hippocampal volume ratios by the frozen status. (I) Distribution of hippocampal volume ratios by age. Panels A-E and F-J share the same y-axis.
Total brain volume across macaque species categorized by social grade.
Distribution of total brain volumes (in cm³) across the four social tolerance grades of the Macaca genus. Each dot represents an individual (n=42), and colors indicate social grade: red (grade 1, intolerant), orange (grade 2), olive (grade 3), and green (grade 4, tolerant). Total brain volume was computed from post-mortem MRI scans, excluding the cerebellum and myelencephalon to control for inter-individual variation in preservation quality. While total volume was included as a covariate in the statistical model, this figure provides a complementary descriptive overview of its distribution across social grades.
Sequence of dissection steps and MRI acquisition.
(A) Craniotomy step: Position of the cadaver and cut site. (B) Steps of scalp and skull removal using a Dremel tool associated with a flex shaft rotary tool. (C) View of the skull after skull and dura removal. (D) Extraction and formaldehyde fixation of the brain. Right lateral view of the brain after a 7-day formaldehyde fixation. (E) SARM Regions (SARM2) and 3D MRI acquisition with atlas (bottom right). Amygdala (purple; Hartig et al., 2021).
Set of photographs of the preparation of the fixed brain for MRI acquisitions.
(A) Air bubble removal stages in a vacuum chamber. The brain is immersed in Fluorinert FC-770 and held in position by the aquarium foam squares. The container is placed in a receptacle to catch any Fluorinert FC-770 that may spill out of the container during the procedure; (B) Placement of the aquarium foam squares inside the container of brain immersed in Fluorinert FC-770 and sealed with parafilm; (C) Placement of the container with a lift foam square to contain the residual air bubble in the top third of the container; (D) Placement of the container in the MRI antenna.
Model quality and coefficients
The R² coefficient of determination of the model indicated a large proportion of variability accounted for by the model (90% credible interval: [0.87, 0.97]). The effect of sex was minimal for the amygdala but more pronounced for the hippocampus (Figures 1 and 2), whereas husbandry had a limited effect on both regions of interest. Amygdala volume increased with social grade (independently of its interaction with age) and with age (independently of its interaction with social grade). However, the interaction between social grade and age suggested that the trajectory of amygdala volume over the lifespan differs across social grades, as detailed below. Total brain volume was included as a covariate in the model to account for interindividual differences in brain size. For descriptive purposes, its distribution across social grades is shown in Figure 1—figure supplement 1.
Parameters of the model.
(A) Parameters of the model for the amygdala volume. (B) Parameters of the model for the hippocampal volume. SG [x]: Social Grade [x] vs Social Grade [1]; SG[x]: Age (10 years): Social Grade-Age interaction.
Despite limited sample size, the interaction between social grade and age suggested a differential trajectory of amygdala volume across the lifespan among different social grades (Figures 1 and 2).
To further assess group differences, we implemented Bayesian hypothesis testing using a Region of Practical Equivalence (ROPE, Kruschke, 2015) approach, with the ROPE defined as ± 0.1 × σ. This method allows classification of results into three categories: (a) a credible difference if the entire posterior interval lies outside the ROPE; (b) an absence of difference if it lies entirely within the ROPE; and (c) inconclusive if it overlaps the ROPE. For the amygdala, social grade 4 (SG4, i.e. tolerant) individuals had credibly larger volumes than social grade 1 (SG1, i.e. intolerant) individuals up to 19 years of age. For the hippocampus, the posterior distribution of the SG4–SG1 difference briefly exceeded the ROPE between approximately 13 and 18 years of age, indicating a credible difference in this age window. Outside this range, the intervals overlapped the ROPE, resulting in inconclusive evidence. However, the 90% posterior intervals remained entirely above zero at all ages, indicating that SG1 individuals never had larger hippocampal volumes than SG4 (Figure 3).
Bayesian hypothesis testing using a Region of Practical Equivalence (ROPE) to assess volume (in mm<sup>3</sup>) differences between Social Grade 4 (SG4; tolerant) and Social Grade 1 (SG1; intolerant) across age, for the amygdala (left) and hippocampus (right).
Curves represent median posterior estimates, and shaded areas show 90% credible intervals. Gray bands indicate the ROPE (±0.1σ). For the amygdala, the difference is credible until ~19 years. For the hippocampus, a credible effect is observed only between ~13 and 18 years.
Predicted data
Figure 4 illustrates how amygdala volume development varies with an individual’s social grade over their lifespan. Two results stand out: first, individuals in Social Grade 1 showed a distinct pattern of amygdala volume development compared to other social grades. Although Grade 1 individuals had a smaller amygdala volume in early years compared to the other Social Grades, the amygdala’s volume variation slope was steeper than for the other Grades (slope with 90% credible intervals [0.6, 11.0]). This increase contrasted with trends observed in Grades 3 (slope with 90% CI [-7.6,–0.9]) and 4 (slope with 90% CI [–8.0, 1.9]), which showed a decrease in volume over time. Individuals in Grade 2 also showed a slight increase in amygdala volume (slope with 90% CI [–4.4, 9.3]), similar to grade 1 but not as steep.
Volume predictions across social tolerance grades of the amygdala and hippocampus.
All panels represent the predictions of the multivariate Bayesian linear model, where all the variables are kept constant (including total brain volumes) in order to represent the effect of age only on the volume of amygdala and hippocampus in mm3. First row (A–D): Predicted amygdala volume across social tolerance grades over the lifespan. (A) Predicted amygdala volume as a function of age for grade 1 (intolerant) individuals. (B) Predicted amygdala volume as a function of age for grade 2 individuals. (C) Predicted amygdala volume as a function of age for grade 3 individuals. (D) Predicted amygdala volume as a function of age for grade 4 (tolerant) individuals. Second row (E–H): Predicted hippocampal volume across social tolerance grades over the lifespan. (E) Predicted hippocampal volume as a function of age for grade 1 individuals. (F) Predicted hippocampal volume as a function of age for grade 2 individuals. (G) Predicted hippocampal volume as a function of age for grade 3 individuals. (H) Predicted hippocampal volume as a function of age for grade 4 individuals. In the plots, the solid lines represent the mean predicted values, and the shaded areas indicate the 90% credible intervals, with each social grade shown in a distinct color.
When comparing Grade 1 and Grade 4, individuals in Grade 4 showed larger amygdala volumes until approximately 19 years of age (Figure 4).
As expected from model predictions, hippocampal volume showed limited variation across age and social grades. ROPE-based hypothesis testing revealed that hippocampal volume in SG1 individuals was never greater than in SG4 individuals, supporting a consistent asymmetry in favor of more tolerant species.
Discussion
We studied for the first time the neuroanatomical foundation of the naturally observed diversity of behavioral traits within the Macaca genus. We have assembled a unique database representing nearly half of the known macaque species, with a variety of ages, sexes, and origins. 12 species of them had never been scanned prior to our study. Our investigation focused on the subcortical structures of the brain and more especially the amygdala. This set of nuclei, sometimes referred to as a hub of brain networks related to sociality and their social lives, is well known for their roles in the stress response (Hölzel et al., 2010), emotional regulation, and social cognition (Noonan et al., 2014; Bickart et al., 2014; Amaral et al., 2003). Based on post-mortem MRI acquisitions from 12 of the 25 macaque species, we showed that amygdala volume correlated with the social tolerance grade and increased with the level of the social grade. Secondly, grade 4 species had a significantly higher amygdala volume at the start of their lives, which decreased over time, compared with grade 1 species, which showed the opposite trend. Finally, further hypothesis testing suggested that species of grade 1 never exhibited larger hippocampus and may have smaller hippocampus around age 15 when compared to those of grade 4. In accordance with our hypotheses (Table 1), our findings substantiated the assertions that (i) social tolerance is rooted in neuroanatomical differences that can be detected at an early stage of individuals’ development, (ii) social styles exert differential influence on subcortical structures throughout individuals’ lifespan and (iii) such phenomena should be mainly driven by the socio-cognitive demands that vary with species social style (as evidenced by the higher amygdala and hippocampus volumes in higher tolerance species).
A neuroanatomical account for social tolerance differences
The social tolerance grades are based on previous ethological observations of behaviors across different species of the genus (Thierry, 2021; Thierry, 2007). From these observations, we identified three major cognitive processes—socio-cognitive demands, social predictability, and inhibitory control (see Table 1)—that underpin the observed behaviors. Among the behaviors we classified with ‘high social-cognitive demand’, several have been previously described in the literature as particularly discriminating between grades 1 and 4. It included greater social network density in grade 4 species (a consequence of, inter alia, low nepotism in tolerant species, facilitating interactions between unaffiliated conspecifics) (Balasubramaniam et al., 2018; Sueur et al., 2011), more complex facial mimics as well as a more complex communication system (Dobson, 2012; Rincon et al., 2023; Scopa and Palagi, 2016; Zannella et al., 2017), a significantly higher rate of reconciliation (Thierry, 2007), and a higher frequency of cooperative behaviors, including male-to-male coalition behaviors (De Waal and Luttrell, 1989; Thierry et al., 2008) in grade 4 species.
At first glance, one may presume that species of lower social tolerance level, that displayed more overall aggressive behaviors, would have a larger amygdala when compared to more tolerant species. In fact, amygdala ablation or activity modulation in macaque monkeys showed that animals displayed less aggressive and different patterns of social behaviors (Amaral, 2002; Bliss-Moreau et al., 2017; Wellman et al., 2016; Forcelli et al., 2017; Raper et al., 2017), supporting the idea that amygdala activity can promote aggressive behaviors. Our study revealed an opposite trend; amygdala was found to be larger in more tolerant species, and this apparent contradiction invites a more integrative view of the amygdala (Adolphs, 2009; Amaral et al., 2003; Pessoa, 2010), not only as a relay for emotional reactivity, but as a multifunctional hub embedded in complex social networks (Bickart et al., 2014). Such complex patterns of behavioral implications are also reflected at the cellular level, as the amygdala is composed of several different nuclei that are broadly connected with other brain areas that may display opposite functions (Zikopoulos et al., 2016; Amiez et al., 2023). Rather than opposing social cognition and emotion, our results support the view that emotional processing is deeply intertwined with social function—both being subserved by overlapping neural circuits (Domínguez-Borràs and Vuilleumier, 2022). It also suggests that additional neural mechanisms, particularly those involving prefrontal and anterior cingulate regions implicated in the top-down regulation of affect and social behavior, may contribute to shaping species differences in social tolerance (Ochsner and Gross, 2008). While our analysis compares social tolerance grades with variations in brain structure, the originality of our framework also lies in introducing three cognitive dimensions that bridge behavioral traits and neural substrates. This intermediate level of interpretation allows us to move beyond simple grade-to-structure associations, toward a more mechanistic understanding of the links between social behavior, cognition, and neuroanatomy.
Amygdala volume has also been shown to correlate positively with social network complexity in grade 1 species, as measured by the social network size of individuals (Sallet et al., 2011; Testard et al., 2022), or by the social status of the animals (Noonan et al., 2014). This supports the idea that the amygdala is sensitive to both structural social features and dynamic aspects of social networks.
Developmental trajectories and life-history plasticity
We are then led to question the origin of the social tolerance effect on amygdala volume, not in terms of a rigid nature versus nurture dichotomy, but in terms of differential developmental trajectories. Cross-fostering experiments (de Waal and Johanowicz, 1993), along with our own results, suggest that social tolerance grades reflect both early, possibly innate predispositions and later environmental shaping. Moreover, the behavioral shifts observed in cross-fostered individuals underscore the plasticity of social style acquisition and the role of early social environment in shaping neural substrates of social behavior. Notably, tolerant species exhibit larger amygdala volumes early in life, while intolerant species show a progressive increase across the lifespan—a pattern that suggests a dual influence of biological programming and cumulative social experience. These environmental influences likely arise from both species-specific social dynamics—such as variations in affiliative behavior and social play (Beltrán Francés et al., 2020)—and broader ecological conditions that structure the demands of social life. The age-related volumetric changes we observed, particularly the divergence in developmental trajectories between tolerant and intolerant species, reinforce this idea and echo previous reports of amygdala growth patterns in humans and macaques (Schumann et al., 2019; Uematsu et al., 2012). Taken together, these elements support the view that social tolerance is not fixed but emerges from the interplay between inherited developmental programs and the specific socio-ecological environments in which individuals mature.
Notably, the developmental trajectory of the amygdala in tolerant species does not align with that of intolerant species or with human developmental patterns (Schumann et al., 2019; Uematsu et al., 2012). This finding suggests that neurodevelopmental pathways may exhibit significant variation among phylogenetically closely related primate species, potentially serving as an effective evolutionary target for adapting socio-ecological behaviors to environmental demands. Moreover, we observed that in old individuals (typically above 19 years), relative amygdala volume in grade 1 species could match that of grade 4 species — despite being significantly smaller earlier in life. Due to a limited sample size of our study, this crossing trend, already accounted for by our continuous age model, should be further investigated. These results call for cautious interpretation of age-related variation and further emphasize the importance of longitudinal studies integrating both behavioral, cognitive, and anatomical data in non-human primates, which would help to better understand the link between social environment and brain development (Song et al., 2021).
Hippocampal volume and social cognitive demands in tolerant species
A credible difference in hippocampal volume favoring SG4 individuals was only revealed between approximately 13 and 18 years of age by our hypothesis testing using a ROPE framework. Outside this range, the difference remained overall positive but inconclusive. This restricted window of significance, along with the unidirectional trend across the lifespan, suggests that increased hippocampal volume may nonetheless be associated with higher social tolerance, at least in adulthood. At first glance, this observation may appear to contrast with literature linking chronic stress to reduced hippocampal size (Kim et al., 2015; Lyons et al., 2007). However, as previously discussed, M. tonkeana (a high-tolerance species) combines elevated basal cortisol levels with a relatively large hippocampus (Sadoughi et al., 2021; Vandeleest et al., 2016), which suggests that glucocorticoid exposure alone does not account for hippocampal variation in this context. Instead, our findings are more consistent with the idea that hippocampal structure reflects species-specific cognitive demands associated with navigating complex and tolerant social environments—such as spatial memory, social recognition, or contextual learning (Han et al., 2021; Sallet et al., 2011). Within the conceptual framework introduced in this study, these results point to the importance of socio-cognitive requirements—rather than social environmental unpredictability or behavioral inhibition abilities—as potential drivers of interspecific variation in hippocampal anatomy. Comparative measurements and observations at the individual level along with in vivo MRI from these same considered individuals may help to further understand how social tolerance can relate to cognitive abilities and its neural underpinning.
Limits of the study and future directions
While our dataset is comprehensive in terms of the number of macaque species included, certain limitations must be acknowledged. For instance, phylogenetic analyses were beyond the reach of this study and integrating these statistical approaches could clarify the extent to which interspecific differences in brain structure and social behavior are due to shared ancestry or convergent evolution (Ghosh et al., 2022; Heuer et al., 2025).
Although we explained some interspecies variability, adding subjects to our database will increase statistical power and will help address potential confounding factors such as age or sex in future studies. One will benefit from additional information about each subject. While considered in our modeling, the social living and husbandry conditions of the individuals in our dataset remain poorly documented. The living environment has been considered, and the size of social groups for certain individuals, particularly for individuals from the CdP, has been recorded. However, these social characteristics have not been determined for all individuals in the dataset. As previously stated, the social environment has a significant impact on the volumetry of certain regions. Furthermore, there is a lack of data regarding the hierarchy of the subjects under study and the stress they experience in accordance with their hierarchical rank and predictability of social outcomes position (McCowan et al., 2022). In addition, our treatment of sex differences was limited. Although sex was included as a covariate in the Bayesian models, the strong imbalance in our dataset—favoring females (2:1 ratio)—precludes robust conclusions about sex-specific trajectories. Some trends, particularly regarding hippocampal volume, suggest potential interactions between sex, age, and social grade, but these effects remain exploratory. Addressing them adequately would require larger and more balanced samples, along with behavioral or hormonal data to capture intra-sexual variability. It is therefore important to recognize that confirmation of our findings should be achieved by analyzing datasets in which all of these confounding factors can be controlled more effectively.
While our study identifies the amygdala as a key subcortical structure associated with interspecific variation in social tolerance, it is important to acknowledge several neuroanatomical limitations. First, our analyses were conducted on the amygdala as a whole, without distinction between its internal nuclei. Although we used the SARM atlas (Hartig et al., 2021), which offers a high-quality parcellation for M. mulatta, the precision of this template does not allow for fully reliable automatic segmentation of amygdala subnuclei across the diverse species included in our dataset. As a result, our volumetric measures may conflate distinct functional subregions, potentially masking more localized effects. In this context, histological approaches remain essential for characterizing fine-grained neuroanatomical differences, as illustrated by Jones et al., 2021, who reported interspecific variation in cell density and serotonergic innervation within the amygdala (Jones et al., 2021). Future studies combining MRI-based volumetry with post-mortem histology would allow more precise identification of which subregions underlie the observed differences in social tolerance.
Cognitive and neural perspectives on our understanding of social tolerance
Future directions linking behavior, cognition, and neuroanatomy could deepen our understanding of the roots of social tolerance among macaque species. This could lead to a better operationalization of the concept that could be applied to a wider range of non-human primate species. From a neural perspective, studying the cortical regions associated with social tolerance represents a promising yet ambitious goal. In fact, there is a variability within primate species in cerebral organization (Amiez et al., 2023; Amiez et al., 2019), which is likely to be found across the Macaca genus. Considering this cerebral variability would require extensive efforts to properly assess interspecies differences, making it beyond the scope of the current study that focuses on subcortical areas. However, as a starting point, exploring the connections between the amygdala, hippocampus, and medial prefrontal cortex could provide crucial insights into the neural correlates of social tolerance. These regions are central to stress regulation, socio-cognitive processing, and decision-making, all of which are likely impacted by social tolerance grades (Caetano et al., 2021; Coplan et al., 2014; Kim et al., 2015; Phelps and LeDoux, 2005; Sapolsky et al., 1990). In humans, repeated positive or stressful experiences have been demonstrated to alter the size of subcortical brain areas such as the hippocampus or amygdala (Davidson and McEwen, 2012) and impair neuroplasticity (Phelps, 2006). Neuronal plasticity and learning have been identified as contributing factors to variations in the ROI volume, including the amygdala and hippocampus, particularly in humans (Maguire et al., 2000; Taren et al., 2013). Additionally, our conceptual framework opens avenues for advanced neuroimaging techniques such as diffusion tensor imaging (DTI) (Howard et al., 2023; Zhang et al., 2013) or multiparametric MRI (Mulholland et al., 2024), which could be used to explore white matter connectivity or microstructural changes. Our findings also emphasize the need to develop individual-level measures of social tolerance (Dubuc et al., 2012; DeTroy et al., 2022). Fine-tuning these measures would allow more precise correlations between behavioral data and neuroanatomical features. By operationalizing the concept of social tolerance on cognitive dimensions, our work aims at enriching the framework through which primate sociality is currently studied.
Conclusion
Our study provides novel insights into the relationship between amygdala volume and social tolerance in macaques, offering an innovative perspective on the neuroanatomical basis of social cognition. Using a comparative approach across 12 macaque species, we uncovered a revealing relationship: low-tolerance species start their life with a smaller amygdala compared to their socially tolerant counterparts. In addition, intolerant species show an increase in amygdala volume, whereas highly tolerant species show the opposite trend. These findings refine conventional views of the amygdala by highlighting its broader role in both emotional regulation and complex social cognition. The observed differences in amygdala volume with respect to social tolerance grades suggest that the development and plasticity of the amygdala seem to be intricately linked to the social environment and experiences of the species. Larger amygdala in socially tolerant species may reflect an enhanced capacity to process complex social information, facilitating better social interactions, cooperative behavior, and conflict management. Alternatively, the observed increase in amygdala volume in socially intolerant species over time may be explained by heightened socio-cognitive demands, rather than being solely attributed to chronic stress or emotional reactivity. While earlier studies emphasized the role of the amygdala in stress response, recent findings are in line with our results, which suggest that amygdala functions extend to broader aspects of social cognition. These findings have profound implications for our understanding of social brain evolution as well as underscoring the importance of developmental stage and the social environment being crucial drivers of neuroanatomical adaptations. In addition, although hippocampal volume showed less pronounced and more variable differences across social grades, a credible effect was observed between 13 and 18 years of age. Across all ages, SG4 individuals consistently exhibited larger hippocampal volumes than SG1, supporting the possibility that this region also contributes to social cognitive processes in tolerant species—especially during developmental phases associated with social maturation. This study, at the interface of primatology and cognitive neuroscience, also provides a framework for investigating the impact of the social environment on brain development and paves the way for future research to unravel the complexities of brain evolution and sociality.
Materials and methodsBrain specimen collection
To allow comprehensive cross-species comparisons in the Macaca genus, a dataset of 42 post-mortem specimens has been constituted through collaborations with multiple research centers, each contributing unique expertise and resources (Supplementary file 1). The collaborating institutions included:
The Centre de Primatologie de l’Université de Strasbourg (CdP)
Provided valuable brain data derived from 20 brain samples. Among those, one sample (M. nigra) was obtained as part of a collaboration with the zoo of Mulhouse (https://www.zoo-mulhouse.com/).
Samples from INDI-PRIME-DE (<xref ref-type="bibr" rid="bib74">Milham et al., 2018</xref>)
The Japan Monkey Center provided 5 post-mortem MRI acquisitions to the dataset (Sakai et al., 2018). Utrecht University: contributed to the dataset with 13 post-mortem MRI acquisitions (Navarrete et al., 2018).
INSERM-Oxford University
5 post-mortem MRI acquisitions came from this collaboration. This addition offered more variety of acquired data mostly in age and sex (Milham et al., 2018).
Ethical considerations
The study was conducted in accordance with ethical guidelines and was approved by the ethical committee of the Centre de Primatologie de l’Université de Strasbourg which is authorized to house NHP (registration B6732636). The research further complied with the EU Directive 2010/63/EU for animal experiments. All subjects from the CdP died of natural or accidental causes; no macaque was euthanized in the sole frame of the project. These specimens originated from CdP, and their collection followed rigorous ethical considerations. The specimens were either obtained from previous collections—where full bodies were preserved in dedicated freezers—or from individuals of the CdP that had died from natural causes. The post-mortem MRI data from INSERM- Oxford University were acquired from deceased animals that died of causes unrelated to the present research project. As such, the research did not require a Home Office License as defined by the Animals (Scientific Procedures) Act 1986 of the United Kingdom.
Brain extraction technique
Post-mortem MRI images acquisition of macaque brains is central to our study, more specifically, in translational studies of homologous brain regions. Brain extraction is a crucial process in neuroscience research for studying the internal brain structure of animals. Through the acquisition at the CdP of 20 post-mortem anatomical MRI scans of brains from six different species of macaques, we were able to refine a brain extraction technique - whether previously frozen or fresh - to minimize specimen handling artefacts and obtain image quality suitable for optimal use by the scientific community. The detailed extraction technique protocol established and used for our brain extractions is available as an appendix. Briefly, the head is reclined forward to expose the neck, muscles are removed to access the atlanto-occipital junction, which is then incised to allow head dislocation (Figure 1—figure supplement 2). An osteotome and hammer are used, ensuring no cerebellar herniation. The skull cap is carefully drilled using a rotary tool and removed (see Figure 1—figure supplement 2A and B and Supplementary file 2 for required tools), and the brain is extracted by severing the olfactory peduncles, internal carotid arteries, and cranial nerves. Specimens are then fixed in 10% buffered formaldehyde for 7 days (see Figure 1—figure supplement 2D) and in phosphate buffered saline (PBS) for 3–4 days before being placed in Fluorinert for MRI acquisition, ensuring minimal air bubbles and optimal image quality (Sébille et al., 2019; see Figure 1—figure supplement 3).
Sampling methods and measurements
Structural images were collected through both the open access databases and collaborations (Milham et al., 2018; Navarrete et al., 2018; Sakai et al., 2018), but also carried out at the IRIS platform of the ICube laboratory in Strasbourg for post-mortem samples kept at the CdP (see Supplementary file 3 for the information relating to the acquisition of anatomical MRI images). The final dataset consists of 42 anatomical scans after pruning data with missing age or sex information (10 individuals), with both T1 and T2-weighted images. Due to their different origins, the images in the dataset did not follow the exact same acquisition protocols (different scanners and acquisition parameters, Supplementary file 3). In addition, post-mortem brain preservation and perfusion protocols are different, which may also influence the images obtained. Volume measurements were performed using a semi-automatic method to register individual images to the Subcortical Atlas of the Rhesus Macaque (SARM; Hartig et al., 2021; Figure 1—figure supplement 2E). Due to the large orientation discrepancies across the research centers, the images were first manually realigned (translation and rotation) with the atlas using ITK-SNAP (Yushkevich et al., 2006), then non-linearly registered using ANTs (Avants et al., 2011). The segmentation maps of the atlas were then transported to the subject space to extract the volume of the regions of interest. Figure 1—figure supplement 2 details the image processing for volume extractions (see Figure 1—figure supplement 3). To ensure the accuracy of the SARM on our dataset, which includes 11 species other than M. mulatta (the species used for SARM development Hartig et al., 2021), we calculated the Dice Similarity Coefficient (DSC; Zou et al., 2004). This was done by manually segmenting, using a tablet (Wacom Cintiq 16 and ITK SNAP software), the amygdala in each acquisition and comparing the overlapping voxels between the manual segmentation and the SARM segmentation. With a DSC of 0.96, we confirm the robust performance of the SARM across our entire dataset.
Final dataset characteristics
The dataset is composed of 12 distinct macaque species with a total of 42 individual specimens for analysis. There is a strong sex imbalance with more females than males. The age range spans from 1 to 44.20 years, with an average age of 18.2±9.4 years (standard deviation) (Figure 5B and D) with two outliers above 35 years old. Most importantly, based on our research question, the social grade distribution of our dataset (Figure 5A) is more represented by grade 1 than grade 4 species, as these species are very rare in zoos or in research centers, and most of them are protected as endangered species. The MRI acquisitions from the 42 individuals were standardized to the NMT template (Jung et al., 2021). Data included amygdala or hippocampus volume and a computed brain ‘total volume’ which only excludes the myelencephalon and the cerebellum for reliability. In fact, the integrity of these subcortical structures heavily depends on the quality and techniques used for brain extraction methods.
Dataset characteristics relative to the social grade.
In red: social tolerance grade 1, orange: grade 2, olive: grade 3, and green: grade 4. (A) Social tolerance grade distribution, where grade 1 is overrepresented due to the prevalence of Macaca mulatta in laboratories. (B) Sex distribution: There was a significant imbalance in the sample, with females outnumbering males (2:1 ratio). (C) Husbandry distribution of the individuals (enclosed and semi-free ranging conditions) (D) Age distribution: The cohort had a relatively even age distribution with a notable peak in the 20 s. (E) The frozen status distribution. (F) Total brain volume distribution, excluding the myelencephalon and cerebellum due to variation in their preservation.
Modeling approach
To investigate the subcortical correlates of social tolerance in macaques, we used a multivariate Bayesian linear model with normal likelihood, the observed data being the amygdala and hippocampus volume. The predictors in our model were the intercept, social grade, age, sex, husbandry, whether the brain had been previously frozen, total volume, the interaction between social grade and age, and the covariance between the observations. We used wide priors, whose locations and scales were derived from the data. We assessed the quality of the model by comparing the predicted data to the observed data, and by checking the R2 of the model. New data was predicted to study the interaction and the age-social grade trajectory, and the difference in volume between social grades. The predictions were made using the model on all social grades, on females aged from 1 to 40, with a total volume of 85 cm3.
Additional informationCompeting interests
No competing interests declared
Author contributions
Conceptualization, Data curation, Investigation, Methodology, Writing – original draft, Writing – review and editing
Data curation, Software, Formal analysis, Methodology, Writing – review and editing
Data curation, Investigation, Methodology, Writing – review and editing
Investigation, Writing – review and editing
Conceptualization, Resources, Funding acquisition, Methodology, Writing – review and editing
Conceptualization, Resources, Data curation, Supervision, Funding acquisition, Investigation, Methodology, Writing – original draft, Project administration, Writing – review and editing
Ethics
The study was conducted in accordance with ethical guidelines and was approved by the ethical committee of the Centre de Primatologie de l'Université; de Strasbourg which is authorized to house NHP (registration B6732636). The research further complied with the EU Directive 2010/63/EU for animal experiments. All subjects from the CdP died of natural or accidental causes; no macaque was euthanized in the sole frame of the project. These specimens originated from CdP, and their collection followed rigorous ethical considerations. The specimens were either obtained from previous collections-where full bodies were preserved in dedicated freezers-or from individuals of the CdP that had died from natural causes. The post-mortem MRI data from INSERM-Oxford University were acquired from deceased animals that died of causes unrelated to the present research project. As such, the research did not require a Home Office License as defined by the Animals (Scientific Procedures) Act 1986 of the United Kingdom.
Additional files
Species and data collection centers in the dataset.
Detailed brain extraction procedure.
Information relating to the acquisition of anatomical MRI images and the procedures for fixing and preserving <italic>post-mortem</italic> samples according to the different institutes.
Data availability
The data associated with this study are available at: https://doi.org/10.17605/OSF.IO/AQMSW.
The following dataset was generated:
LamyJ2025Neuroanatomical Foundations of Macaques’ Social Tolerance: Insights from Subcortical StructuresOpen Science Framework10.17605/OSF.IO/AQMSW
Acknowledgements
The authors are grateful to the University of Strasbourg, the CNRS and Silabe (https://silabe.com/) for supporting this research and providing expert animal care. This work was further funded by ANR-21-CE37-0016 to SB and JS. This work is co-funded by the French State Region contract CPER I2MT (2014-2021), R-IRM (2021-2027) and by the European Union through the European Regional Development Fund “FEDER Grand Est”. This work was performed on the IRIS platform of ICube lab, member of France Life Imaging network (grant ANR 11 INBS 0006). We extend our gratitude to the PRIME-DE open science initiative, particularly the Utrecht database, as well as the Japan Monkey Center for providing access to their open science resources. Warm thanks are extended to Brice Lefaux and his staff at Mulhouse Zoo for the collection of brain samples being made possible. Additionally, we sincerely thank Aurore de Cauwer (from ICube) for her invaluable assistance at the early stages in the MRI data acquisition. The Wellcome Centre for Integrative Neuroimaging is supported by core funding from the Wellcome Trust (203139/Z/16/Z).
ReferencesAdamsMJMajoloBOstnerJSchülkeODe MarcoAThierryBEngelhardtAWiddigAGeraldMSWeissA2015Personality structure and social style in macaquesJournal of Personality and Social Psychology10933835310.1037/pspp000004126030054AdolphsR2009The social brain: neural basis of social knowledgeAnnual Review of Psychology6069371610.1146/annurev.psych.60.110707.16351418771388AguenounonGAllritzMAltschulDBallestaSBeaudABohnMBornbuschSBrandãoABrooksJBugnyarTBurkartJBustamanteLCallJCanteloupCCaoCCasparKda SilvaDde SousaADeTroySDuguidSEppleyTFichtelCFischerJGongCGrangeJGrebeNHanusDHaunDHauxLHéjja-BrichardYHelmanAHernadiIHernandez-AguilarRAHerrmannEHopperLHowardLHuangLHuskissonSJacobsIJinZJolyMKanoFKeuppSKieferEKnakkerBKóczánKKrausLKwokSCLefrançoisMLewisLLiuSLlorenteMLonsdorfELoyantLMajeckaKMauritsLMeunierHMobiliFMorinoLMotes-RodrigoANijmanVIhomiCPerssonTPietraszewskiDReátiga ParrishJRoigASánchez-AmaroASatoYSauciucGASchrockASchweinfurthMSeedAShearerCŠlipogorVSuYSutherlandKTanJTaylorDTroisiCVölterCWarrenEWatzekJZablocki-ThomasPManyPrimates2022The evolution of primate short-term memoryAnimal Behavior and Cognition942851610.26451/abc.09.04.06.2022AmaralDG2002The primate amygdala and the neurobiology of social behavior: implications for understanding social anxietyBiological Psychiatry51111710.1016/S0006-3223(01)01307-5AmaralDGBaumanMDCapitanioJPLavenexPMasonWAMauldin-JourdainMLMendozaSP2003The amygdala: is it an essential component of the neural network for social cognition?Neuropsychologia4151752210.1016/S0028-3932(02)00310-XAmiezCSalletJHopkinsWDMeguerditchianAHadj-BouzianeFBen HamedSWilsonCREProcykEPetridesM2019Sulcal organization in the medial frontal cortex provides insights into primate brain evolutionNature Communications10343710.1038/s41467-019-11347-x31366944AmiezCSalletJGiacomettiCVerstraeteCGandauxCMorel-LatourVMeguerditchianAHadj-BouzianeFBen HamedSHopkinsWDProcykEWilsonCREPetridesM2023A revised perspective on the evolution of the lateral frontal cortex in primatesScience Advances9eadf944510.1126/sciadv.adf944537205762AvantsBBTustisonNJSongGCookPAKleinAGeeJC2011A reproducible evaluation of ANTs similarity metric performance in brain image registrationNeuroImage542033204410.1016/j.neuroimage.2010.09.02520851191BalasubramaniamKNDittmarKBermanCMButovskayaMCooperMAMajoloBOgawaHSchinoGThierryBDe WaalFBM2012Hierarchical steepness, counter-aggression, and macaque social style scaleAmerican Journal of Primatology7491592510.1002/ajp.2204422688756BalasubramaniamKNBeisnerBABermanCMDe MarcoADuboscqJKoiralaSMajoloBMacIntoshAJMcFarlandRMolestiSOgawaHPetitOSchinoGSosaSSueurCThierryBde WaalFBMMcCowanB2018The influence of phylogeny, social style, and sociodemographic factors on macaque social network structureAmerican Journal of Primatology80e2272710.1002/ajp.2272729140552Beltrán FrancésVCastellano-NavarroAIlla MaulanyRNgakanPOMacIntoshAJJLlorenteMAmiciF2020Play behavior in immature moor macaques (Macaca maura) and Japanese macaques (Macaca fuscata)American Journal of Primatology82e2319210.1002/ajp.2319232882065BickartKCWrightCIDautoffRJDickersonBCBarrettLF2011Amygdala volume and social network size in humansNature Neuroscience1416316410.1038/nn.272421186358BickartKCDickersonBCBarrettLF2014The amygdala as a hub in brain networks that support social lifeNeuropsychologia6323524810.1016/j.neuropsychologia.2014.08.01325152530Bliss-MoreauEMoadabGSantistevanAAmaralDG2017The effects of neonatal amygdala or hippocampus lesions on adult social behaviorBehavioural Brain Research32212313710.1016/j.bbr.2016.11.05228017854BouretSParadisEPratSCastroLPerezPGilissenEGarciaC2024Linking the evolution of two prefrontal brain regions to social and foraging challenges in primateseLife12RP8778010.7554/eLife.8778039468920BrownCRechRRTorresF2009A Field Manual for Collection of Specimens to Enhance Diagnosis of Animal DiseasesBoca Publications Group, IncorporatedCaetanoIAmorimLSoaresJMFerreiraSCoelhoAReisJSantosNCMoreiraPSMarquesPMagalhãesREstevesMPicó-PérezMSousaN2021Amygdala size varies with stress perceptionNeurobiology of Stress1410033410.1016/j.ynstr.2021.10033434013000CarloCNStefanacciLSemendeferiKStevensCF2010Comparative analyses of the neuron numbers and volumes of the amygdaloid complex in old and new world primatesThe Journal of Comparative Neurology5181176119810.1002/cne.2226420148438CooperEBBrentLJNSnyder-MacklerNSinghMSenguptaAKhatiwadaSMalaivijitnondSQi HaiZHighamJP2022The rhesus macaque as a success story of the AnthropoceneeLife11e7816910.7554/eLife.7816935801697CoplanJDFathyHMJackowskiAPTangCYPereraTDMathewSJMartinezJAbdallahCGDworkAJPantolGCarpenterDGormanJMNemeroffCBOwensMJKaffmanAKaufmanJ2014Early life stress and macaque amygdala hypertrophy: preliminary evidence for a role for the serotonin transporter geneFrontiers in Behavioral Neuroscience834210.3389/fnbeh.2014.0034225339875CordsM2012The behavior, ecology, and social evolution of cercopithecine monkeysMitaniJCCallJKappelerPMPalombitRASilkJBThe Evolution of Primate SocietiesUniversity of Chicago Press91112DavenportATGrantKASzeligaKTFriedmanDPDaunaisJB2014Standardized method for the harvest of nonhuman primate tissue optimized for multiple modes of analysesCell and Tissue Banking159911010.1007/s10561-013-9380-223709130DavidsonRJMcEwenBS2012Social influences on neuroplasticity: stress and interventions to promote well-beingNature Neuroscience1568969510.1038/nn.309322534579DemariaCThierryB2001A comparative study of reconciliation in rhesus and Tonkean macaquesBehaviour13839741010.1163/15685390152032514DeTroySEHaunDBMvan LeeuwenEJC2022What isn’t social tolerance? The past, present, and possible future of an overused term in the field of primatologyEvolutionary Anthropology31304410.1002/evan.2192334460130de VriesHStevensJMGVervaeckeH2006Measuring and testing the steepness of dominance hierarchiesAnimal Behaviour7158559210.1016/j.anbehav.2005.05.015de WaalFBMLuttrellLM1985The formal hierarchy of rhesus macaques: an investigation of the bared-teeth displayAmerican Journal of Primatology9738510.1002/ajp.135009020232102494De WaalFBMLuttrellLM1989Toward a comparative socioecology of the genus Macaca: different dominance styles in rhesus and stumptail monkeysAmerican Journal of Primatology198310910.1002/ajp.135019020331964014de WaalFBJohanowiczDL1993Modification of reconciliation behavior through social experience: an experiment with two macaque speciesChild Development6489790810.2307/11312258339702DobsonSD2012Coevolution of facial expression and social tolerance in macaquesAmerican Journal of Primatology7422923510.1002/ajp.2199124006541Domínguez-BorràsJVuilleumierP2022Amygdala function in emotion, cognition, and behaviorDomínguez-BorràsJVuilleumierPHandbook of Clinical NeurologyElsevier35938010.1016/B978-0-12-823493-8.00015-8DuboscqJMichelettaJAgilMHodgesKThierryBEngelhardtA2013Social tolerance in wild female crested macaques (Macaca nigra) in Tangkoko-Batuangus Nature Reserve, Sulawesi, IndonesiaAmerican Journal of Primatology7536137510.1002/ajp.2211423307343DuboscqJAgilMEngelhardtAThierryB2014The function of postconflict interactions: new prospects from the study of a tolerant species of primateAnimal Behaviour8710712010.1016/j.anbehav.2013.10.018DubucCHughesKDCascioJSantosLR2012Social tolerance in a despotic primate: co-feeding between consortship partners in rhesus macaquesAmerican Journal of Physical Anthropology148738010.1002/ajpa.2204322415860DunbarRIM2009The social brain hypothesis and its implications for social evolutionAnnals of Human Biology3656257210.1080/0301446090296028919575315DunbarRIMShultzS2025Self-control has a social role in primates, but not in other mammals or birdsScientific Reports151756610.1038/s41598-025-99523-640394114FairbanksLA1990Reciprocal benefits of allomothering for female vervet monkeysAnimal Behaviour4055356210.1016/S0003-3472(05)80536-6FlackJCGirvanMde WaalFBMKrakauerDC2006Policing stabilizes construction of social niches in primatesNature43942642910.1038/nature0432616437106ForcelliPAWaguespackHFMalkovaL2017Defensive vocalizations and motor asymmetry triggered by disinhibition of the periaqueductal gray in non-human primatesFrontiers in Neuroscience1116310.3389/fnins.2017.0016328424576FranklinMSKraemerGWSheltonSEBakerEKalinNHUnoH2000Gender differences in brain volume and size of corpus callosum and amygdala of rhesus monkey measured from MRI imagesBrain Research85226326710.1016/s0006-8993(99)02093-410678751FreebergTMDunbarRIMOrdTJ2012Social complexity as a proximate and ultimate factor in communicative complexityPhilosophical Transactions of the Royal Society of London. Series B, Biological Sciences3671785180110.1098/rstb.2011.021322641818GhoshAThakurMSinghSKDuttaRSharmaLKChandraKBanerjeeD2022The Sela macaque (Macaca selai) is a distinct phylogenetic species that evolved from the Arunachal macaque following allopatric speciationMolecular Phylogenetics and Evolution17410751310.1016/j.ympev.2022.10751335605928GumertMDHoMHR2008The trade balance of grooming and its coordination of reciprocation and tolerance in Indonesian long-tailed macaques (Macaca fascicularis)Primates; Journal of Primatology4917618510.1007/s10329-008-0089-y18545935HaleyGEMcGuireABerteau-PavyDWeissAPatelRMessaoudiIUrbanskiHFRaberJ2012Measures of anxiety, amygdala volumes, and hippocampal scopolamine phMRI response in elderly female rhesus macaquesNeuropharmacology6238539010.1016/j.neuropharm.2011.08.01421867720HanMJiangGLuoHShaoY2021Neurobiological bases of social networksFrontiers in Psychology1262633710.3389/fpsyg.2021.62633733995181HartigRGlenDJungBLogothetisNKPaxinosGGarza-VillarrealEAMessingerAEvrardHC2021The subcortical atlas of the rhesus macaque (SARM) for neuroimagingNeuroImage23511799610.1016/j.neuroimage.2021.11799633794360HeldstabSAIslerKGraberSMSchuppliCvan SchaikCP2022The economics of brain size evolution in vertebratesCurrent Biology32R697R70810.1016/j.cub.2022.04.09635728555HeuerKTrautNAristideLAlaviSFHerbinMMarsRBMylapalliRNajafipashakiSSakaiTSantinMDBorrellVToroR2025Principles of neocortical organisation and behaviour in primatesbioRxiv10.1101/2025.07.17.665410HillDAOkayasuN1995Absence of “Youngest Ascendancy” in the dominance relations of sisters in wild Japanese Macaques (Macaca fuscata Yakui)Behaviour13236737910.1163/156853995X00612HölzelBKCarmodyJEvansKCHogeEADusekJAMorganLPitmanRKLazarSW2010Stress reduction correlates with structural changes in the amygdalaSocial Cognitive and Affective Neuroscience5111710.1093/scan/nsp03419776221HowardAFDHuszarINSmartACottaarMDaubneyGHanayikTKhrapitchevAAMarsRBMollinkJScottCSibsonNRSalletJJbabdiSMillerKL2023An open resource combining multi-contrast MRI and microscopy in the macaque brainNature Communications14432010.1038/s41467-023-39916-137468455HowellBRGrandAPMcCormackKMShiYLaPrarieJLMaestripieriDStynerMASanchezMM2014Early adverse experience increases emotional reactivity in juvenile rhesus macaques: relation to amygdala volumeDevelopmental Psychobiology561735174610.1002/dev.2123725196846IsaTYamaneIHamaiMInagakiH2009Japanese macaques as laboratory animalsExperimental Animals5845145710.1538/expanim.58.45119897928JolyMMichelettaJDe MarcoALangermansJASterckEHMWallerBM2017Comparing physical and social cognitive skills in macaque species with different degrees of social toleranceProceedings of the Royal Society B2842016273810.1098/rspb.2016.2738JonesDNErwinJMSherwoodCCHofPRRaghantiMA2021A comparison of cell density and serotonergic innervation of the amygdala among four macaque speciesThe Journal of Comparative Neurology5291659166810.1002/cne.2504833022073JungBTaylorPASeidlitzJSponheimCPerkinsPUngerleiderLGGlenDMessingerA2021A comprehensive macaque fMRI pipeline and hierarchical atlasNeuroImage23511799710.1016/j.neuroimage.2021.11799733789138KanaiRBahramiBRoylanceRReesG2012Online social network size is reflected in human brain structureProceedings. Biological Sciences2791327133410.1098/rspb.2011.195922012980KimEJPellmanBKimJJ2015Stress effects on the hippocampus: a critical reviewLearning & Memory2241141610.1101/lm.037291.114KingJMRoth-JohnsonLDoddDCNewsomME2013The Necropsy Book: A Guide for Veterinary Students, Residents, Clinicians, Pathologists and Biological ResearchersCollege of Veterinary MedicineKruschkeJK2015Doing Bayesian Data Analysis - A Tutorial with R, JAGS, and StanAcademic Press10.1016/B978-0-12-405888-0.00008-8KutsukakeN2000Matrilineal rank Inheritance varies with absolute rank in Japanese macaquesPrimates; Journal of Primatology4132133510.1007/BF0255760130545183LiebalKWallerBMBurrowsAMSlocombeKE2014Primate Communication: A Multimodal ApproachCambridge University Press10.1017/CBO9781139018111LoyantLWallerBMMichelettaJMeunierHBallestaSJolyM2023Tolerant macaque species are less impulsive and reactiveAnimal Cognition261453146610.1007/s10071-023-01789-837245190LyonsDMYangCSawyer-GloverAMMoseleyMESchatzbergAF2001Early life stress and inherited variation in monkey hippocampal volumesArchives of General Psychiatry581145115110.1001/archpsyc.58.12.114511735843LyonsDMParkerKJZeitzerJMBuckmasterCLSchatzbergAF2007Preliminary evidence that hippocampal volumes in monkeys predict stress levels of adrenocorticotropic hormoneBiological Psychiatry621171117410.1016/j.biopsych.2007.03.01217573043MaestripieriD1994Social structure, infant handling, and mothering styles in group-living old world monkeysInternational Journal of Primatology1553155310.1007/BF02735970MaguireEAGadianDGJohnsrudeISGoodCDAshburnerJFrackowiakRSFrithCD2000Navigation-related structural change in the hippocampi of taxi driversPNAS974398440310.1073/pnas.07003959710716738MaranesiMLiviAFogassiLRizzolattiGBoniniL2014Mirror neuron activation prior to action observation in a predictable contextThe Journal of Neuroscience34148271483210.1523/JNEUROSCI.2705-14.201425378150MassenJJMvan den BergLMSpruijtBMSterckEHM2010Generous leaders and selfish underdogs: pro-sociality in despotic macaquesPLOS ONE5e973410.1371/journal.pone.000973420305812McCowanBVandeleestJBalasubramaniamKHsiehFNathmanABeisnerB2022Measuring dominance certainty and assessing its impact on individual and societal health in a nonhuman primate model: a network approachPhilosophical Transactions of the Royal Society B3772020043810.1098/rstb.2020.0438MeguerditchianAMarieDMargiotoudiKRothMNazarianBAntonJLClaidièreN2021Baboons (Papio anubis) living in larger social groups have bigger brainsEvolution and Human Behavior42303410.1016/j.evolhumbehav.2020.06.010MeyerJSHamelAF2014Models of stress in nonhuman primates and their relevance for human psychopathology and endocrine dysfunctionILAR Journal5534736010.1093/ilar/ilu02325225311MichelettaJWallerBMPanggurMRNeumannCDuboscqJAgilMEngelhardtA2012Social bonds affect anti-predator behaviour in a tolerant species of macaque, Macaca nigraProceedings. Biological Sciences2794042405010.1098/rspb.2012.147022859593MilhamMPAiLKooBXuTAmiezCBalezeauFBaxterMGBlezerELABrochierTChenACroxsonPLDamatacCGDehaeneSEverlingSFairDAFleysherLFreiwaldWFroudist-WalshSGriffithsTDGuedjCHadj-BouzianeFBen HamedSHarelNHibaBJarrayaBJungBKastnerSKlinkPCKwokSCLalandKNLeopoldDALindenforsPMarsRBMenonRSMessingerAMeunierMMokKMorrisonJHNacefJNagyJRiosMOPetkovCIPinskMPoirierCProcykERajimehrRReaderSMRoelfsemaPRRudkoDARushworthMFSRussBESalletJSchmidMCSchwiedrzikCMSeidlitzJSeinJShmuelASullivanELUngerleiderLThieleATodorovOSTsaoDWangZWilsonCREYacoubEYeFQZarcoWZhouYMarguliesDSSchroederCE2018An open resource for non-human primate imagingNeuron100617410.1016/j.neuron.2018.08.03930269990MulhollandMMHechtEWesleyMJHopkinsWD2024Long term impacts of early social environment on chimpanzee white matterScientific Reports142987910.1038/s41598-024-81238-939622904NavarreteAFBlezerELAPagnottaMde VietESMTodorovOSLindenforsPLalandKNReaderSM2018Primate brain anatomy: new volumetric mri measurements for neuroanatomical studiesBrain, Behavior and Evolution9110911710.1159/00048813629894995NoonanMPSalletJMarsRBNeubertFXO’ReillyJXAnderssonJLMitchellASBellAHMillerKLRushworthMFS2014A neural circuit covarying with social hierarchy in macaquesPLOS Biology12e100194010.1371/journal.pbio.1001940OchsnerKNGrossJJ2008Cognitive emotion regulation: insights from social cognitive and affective neuroscienceCurrent Directions in Psychological Science1715315810.1111/j.1467-8721.2008.00566.x25425765ParkinsonCKleinbaumAMWheatleyT2017Spontaneous neural encoding of social network positionNature Human Behaviour11710.1038/s41562-017-0072PassinghamREWiseSPPassinghamREWiseSP2012The Neurobiology of the Prefrontal Cortex: Anatomy, Evolution, and the Origin of Insight, Oxford Psychology SeriesOxford University PressPatzeltAKoppGHNdaoIKalbitzerUZinnerDFischerJ2014Male tolerance and male–male bonds in a multilevel primate societyPNAS111147401474510.1073/pnas.1405811111PerelmanPJohnsonWERoosCSeuánezHNHorvathJEMoreiraMAMKessingBPontiusJRoelkeMRumplerYSchneiderMPCSilvaAO’BrienSJPecon-SlatteryJ2011A molecular phylogeny of living primatesPLOS Genetics7e100134210.1371/journal.pgen.100134221436896PessoaL2010Emotion and cognition and the amygdala: from “what is it?” to “what’s to be done?”Neuropsychologia483416342910.1016/j.neuropsychologia.2010.06.03820619280PetitOAbeggCThierryB1997A comparative study of aggression and conciliation in three cercopithecine monkeys (Macaca fuscata, Macaca Nigra, Papio Papio)Behaviour13441543210.1163/156853997X00610PetitOBertrandFThierryB2008Social play in crested and Japanese macaques: testing the covariation hypothesisDevelopmental Psychobiology5039940710.1002/dev.2030518393281PhelpsEALeDouxJE2005Contributions of the amygdala to emotion processing: from animal models to human behaviorNeuron4817518710.1016/j.neuron.2005.09.02516242399PhelpsEA2006Emotion and cognition: insights from studies of the human amygdalaAnnual Review of Psychology57275310.1146/annurev.psych.56.091103.07023416318588RaperJWilsonMSanchezMPayneCBachevalierJ2017Increased anxiety-like behaviors, but blunted cortisol stress response after neonatal hippocampal lesions in monkeysPsychoneuroendocrinology76576610.1016/j.psyneuen.2016.11.01827888771ReboutNDe MarcoALoneJCSannaACozzolinoRMichelettaJSterckEHMLangermansJAMLemassonAThierryB2020Tolerant and intolerant macaques show different levels of structural complexity in their vocal communicationProceedings of the Royal Society B2872020043910.1098/rspb.2020.0439RinconAVWallerBMDuboscqJMielkeAPérezCClarkPRMichelettaJ2023Higher social tolerance is associated with more complex facial behavior in macaqueseLife12RP8700810.7554/eLife.8700837787008SadoughiBLacroixLBerbesqueCMeunierHLehmannJ2021Effects of social tolerance on stress: hair cortisol concentrations in the tolerant Tonkean macaques (Macaca tonkeana) and the despotic long-tailed macaques (Macaca fascicularis)Stress241033104110.1080/10253890.2021.199844334756152SakaiTHataJOhtaHShintakuYKimuraNOgawaYSogabeKMoriSOkanoHJHamadaYShibataSOkanoHOishiK2018The Japan Monkey Centre Primates Brain Imaging Repository for comparative neuroscience: an archive of digital records including records for endangered speciesPrimates; Journal of Primatology5955357010.1007/s10329-018-0694-330357587SakaiTHataJShintakuYOhtaHSogabeKMoriSMiyabe-NishiwakiTOkanoHJHamadaYHirabayashiTMinamimotoTSadatoNOkanoHOishiK2023The Japan Monkey Centre Primates Brain Imaging Repository of high-resolution postmortem magnetic resonance imaging: The second phase of the archive of digital recordsNeuroImage27312009610.1016/j.neuroimage.2023.12009637031828SalletJMarsRBNoonanMPAnderssonJLO’ReillyJXJbabdiSCroxsonPLJenkinsonMMillerKLRushworthMFS2011Social network size affects neural circuits in macaquesScience33469770010.1126/science.121002722053054SapolskyRMUnoHRebertCSFinchCE1990Hippocampal damage associated with prolonged glucocorticoid exposure in primatesThe Journal of Neuroscience102897290210.1523/JNEUROSCI.10-09-02897.19902398367SchumannCMScottJALeeABaumanMDAmaralDG2019Amygdala growth from youth to adulthood in the macaque monkeyThe Journal of Comparative Neurology5273034304510.1002/cne.2472831173365ScopaCPalagiE2016Mimic me while playing! Social tolerance and rapid facial mimicry in macaques (Macaca tonkeana and Macaca fuscata)Journal of Comparative Psychology13015316110.1037/com000002827078077ScottJAGraysonDFletcherELeeABaumanMDSchumannCMBuonocoreMHAmaralDG2016Longitudinal analysis of the developing rhesus monkey brain using magnetic resonance imaging: birth to adulthoodBrain Structure & Function2212847287110.1007/s00429-015-1076-x26159774SébilleSBRollandASWelterMLBardinetESantinMD2019Post mortem high resolution diffusion MRI for large specimen imaging at 11.7 T with 3D segmented echo-planar imagingJournal of Neuroscience Methods31122223410.1016/j.jneumeth.2018.10.01030321565ShatilASMatsudaKMFigleyCR2016A method for whole brain Ex Vivo magnetic resonance imaging with minimal susceptibility artifactsFrontiers in Neurology720810.3389/fneur.2016.0020827965620SilkJB1999Male bonnet macaques use information about third-party rank relationships to recruit alliesAnimal Behaviour58455110.1006/anbe.1999.112910413539SilkJB2002Kin selection in primate groupsInternational Journal of Primatology2384987510.1023/A:1015581016205SilkJBAlbertsSCAltmannJ2003Social bonds of female baboons enhance infant survivalScience3021231123410.1126/science.108858014615543SongXGarcía-SaldivarPKindredNWangYMerchantHMeguerditchianAYangYSteinEABradberryCWBen HamedSJedemaHPPoirierC2021Strengths and challenges of longitudinal non-human primate neuroimagingNeuroImage23611800910.1016/j.neuroimage.2021.11800933794361SueurCPetitODe MarcoAJacobsATWatanabeKThierryB2011A comparative network analysis of social style in macaquesAnimal Behaviour8284585210.1016/j.anbehav.2011.07.020SuomiSJ2008Attachment in rhesus monkeysSuomiSJHandbook of Attachment: Theory, Research, and Clinical ApplicationsThe Guilford Press173191TarenAACreswellJDGianarosPJ2013Dispositional mindfulness co-varies with smaller amygdala and caudate volumes in community adultsPLOS ONE8e6457410.1371/journal.pone.006457423717632TestardCBrentLJNAnderssonJChiouKLNegron-Del ValleJEDeCasienARAcevedo-IthierAStockMKAntónSCGonzalezOWalkerCSFoxleySCompoNRBaumanSRuiz-LambidesAVMartinezMISkeneJHPHorvathJEUnitCBRHighamJPMillerKLSnyder-MacklerNMontagueMJPlattMLSalletJ2022Social connections predict brain structure in a multidimensional free-ranging primate societyScience Advances8eabl579410.1126/sciadv.abl579435417242ThavarajahRMudimbaimannarVKElizabethJRaoUKRanganathanK2012Chemical and physical basics of routine formaldehyde fixationJournal of Oral and Maxillofacial Pathology1640040510.4103/0973-029X.10249623248474ThierryBSapolskyR2000Covariation of conflict management patterns across macaque speciesAureliFNatural Conflict ResolutionUniversity of California Press10612810.1525/9780520924932-010ThierryBSinghMKaumannsW2004Macaque Societies: A Model for the Study of Social OrganizationCambridge University PressThierryB2007Unity in diversity: lessons from macaque societiesEvolutionary Anthropology1622423810.1002/evan.20147ThierryBAureliFNunnCLPetitOAbeggCde WaalFBM2008A comparative study of conflict resolution in macaques: insights into the nature of trait covariationAnimal Behaviour7584786010.1016/j.anbehav.2007.07.006ThierryBBermanC2010Variation in kin bias: species differences and time constraints in macaquesBehaviour1471863188710.1163/000579510X539691ThierryB2017Macaque (macaca)ThierryBThe International Encyclopedia of PrimatologyJohn Wiley & Sons, Ltd1410.1002/9781119179313ThierryB2021Where do we stand with the covariation framework in primate societies?American Journal of Biological Anthropology178 Suppl 7452510.1002/ajpa.2444136787776TodorovOSWeisbeckerVGilissenEZillesKde SousaAA2019Primate hippocampus size and organization are predicted by sociality but not dietProceedings. Biological Sciences2862019171210.1098/rspb.2019.171231662078TottenhamNHareTAQuinnBTMcCarryTWNurseMGilhoolyTMillnerAGalvanADavidsonMCEigstiI-MThomasKMFreedPJBoomaESGunnarMRAltemusMAronsonJCaseyBJ2010Prolonged institutional rearing is associated with atypically large amygdala volume and difficulties in emotion regulationDevelopmental Science13466110.1111/j.1467-7687.2009.00852.x20121862UematsuAMatsuiMTanakaCTakahashiTNoguchiKSuzukiMNishijoH2012Developmental trajectories of amygdala and hippocampus from infancy to early adulthood in healthy individualsPLOS ONE7e4697010.1371/journal.pone.004697023056545VandeleestJJBeisnerBAHannibalDLNathmanACCapitanioJPHsiehFAtwillERMcCowanB2016Decoupling social status and status certainty effects on health in macaques: a network approachPeerJ4e239410.7717/peerj.239427672495WallerBMLiebalKBurrowsAMSlocombeKE2013How can a multimodal approach to primate communication help us understand the evolution of communication?Evolutionary Psychology1153854910.1177/14747049130110030523864293WallerBMWhitehouseJMichelettaJ2016Macaques can predict social outcomes from facial expressionsAnimal Cognition191031103610.1007/s10071-016-0992-327155662WellmanLLForcelliPAAguilarBLMalkovaL2016Bidirectional control of social behavior by activity within basolateral and central amygdala of primatesThe Journal of Neuroscience368746875610.1523/JNEUROSCI.0333-16.201627535919WhitehouseJClarkPRRobinsonRLReesKO’CallaghanOKimockCMWithamCLWallerBM2024Facial expressivity in dominant macaques is linked to group cohesionProceedings. Biological Sciences2912024098410.1098/rspb.2024.098439013427YushkevichPAPivenJHazlettHCSmithRGHoSGeeJCGerigG2006User-guided 3D active contour segmentation of anatomical structures: significantly improved efficiency and reliabilityNeuroImage311116112810.1016/j.neuroimage.2006.01.01516545965ZannellaAStanyonRPalagiE2017Yawning and social styles: Different functions in tolerant and despotic macaques (Macaca tonkeana and Macaca fuscata)Journal of Comparative Psychology13117918810.1037/com000006228318293ZhangDGuoLZhuDLiKLiLChenHZhaoQHuXLiuT2013Diffusion tensor imaging reveals evolution of primate brain architecturesBrain Structure & Function2181429145010.1007/s00429-012-0468-423135357ZikopoulosBJohnYJGarcía-CabezasMÁBunceJGBarbasH2016The intercalated nuclear complex of the primate amygdalaNeuroscience33026729010.1016/j.neuroscience.2016.05.05227256508ZouKHWarfieldSKBharathaATempanyCMCKausMRHakerSJWellsWMJoleszFAKikinisR2004Statistical validation of image segmentation quality based on a spatial overlap indexAcademic Radiology1117818910.1016/s1076-6332(03)00671-814974593Appendix 1Detailed brain extraction procedure
The first part of the acquisition of brain MRI images relies on the extraction of brain specimens. All the required materials are listed in Supplementary file 1 and have been curated through literature recommendations (Brown et al., 2009; Davenport et al., 2014; King et al., 2013; Shatil et al., 2016) as well as through the realization of the procedure itself.
As it was the first time at the CdP that brain specimens were extracted, the development of a refined brain extraction technique played a central role in optimizing the quality of the acquired brain images. This technique, based on the literature, was meticulously applied to 17 post-mortem anatomical and DTI (if the specimen was not frozen) MRI scans. We optimally prepared through familiarizing ourselves with the technique and handling instruments such as the oscillating saw with a first brain extraction of a poor conditioned brain specimen (bad freezing condition). Through this first trial, we were able to adjust the following procedure as well as the chosen cutting landmarks. The brain extraction sequence consists of the following steps:
Head dislocation
The animal is in supine position, with its head pulled dorsally to extend the neck (Brown et al., 2009). Then, the muscle mass of the neck has to be removed to expose the atlantooccipital junction. The junction is then incised, employing a back-and-forth motion to enable the passage of a knife or hammer axis between the cartilage (Brown et al., 2009).
Adjustment for frozen specimens
For frozen specimens, a distinct approach through the atlantooccipital junction must be adopted. The section is performed with an osteotome and hammer (Figure 1—figure supplement 1A). Subsequently, confirmation of the absence of cerebellar protrusion through the foramen magnum is required and essential for ensuring the integrity of the specimens. If not, it would indicate cerebellar herniation and the presence of associated lesions in this brain structure (Davenport et al., 2014).
The head circumference was measured using a measuring tape during data collection. The average circumference of a macaque brain in our dataset is 30.5±8.7 cm. We determined the amount of formaldehyde required based on the average volume of a macaque brain. This average volume is 89.2±1.9 (SEM) for male individuals and 70.8±0.72 cm3 for female individuals (Franklin et al., 2000; Scott et al., 2016). The amount of 4% formaldehyde buffered solution (pH = 6.9, Sigma-Aldrich) required to fix the brain should follow the volume ratio of tissue to be fixed to formaldehyde of 1:10 (Thavarajah et al., 2012), that is, a minimum of one liter of formaldehyde.
Skull cap removal
The removal of the skull cap is the most meticulous part of the procedure aimed at providing access to the brain. This process starts with a longitudinal incision of the scalp from the anterior fontanel cranial suture to the foramen magnum. A second incision is made perpendicular to the first, along the coronal suture. The exposed skull surface underwent thorough cleaning with 70% ethanol, followed by drying with gauze pads. The bony skull cap was then delicately excised using a rotary tool (Figure 1—figure supplement 1B).
Brain extraction
The extraction of the brain from the skull was conducted with care, especially for fresh specimens, as the tissues are very soft and breakable. Removal of the dura mater, cerebellum tent, and false brain is performed using a bony cap (Brown et al., 2009). Afterwards, the head is positioned vertically and some gentle taps on the table facilitate the gradual detachment of the brain from the skull. Employing a fluted probe, the olfactory peduncles, internal carotid arteries, and cranial nerves are delicately severed (King et al., 2013). The pineal gland is commonly found as a single white firm conical mass suspended at the midline of the skull cap and attached to the meninges (King et al., 2013). In addition, in many animals, the choroid plexus is visible as two reddish masses in a position similar to or slightly in front of the pineal gland (King et al., 2013). Once the brain is fully extracted, it is placed in one of the hemispheric cups. Frozen specimens are thawed in water at room temperature before placing them in the cup (frozen tissue combined with formaldehyde fixation creates an aqueous insulating layer, altering fixation of the internal brain structures) (Figure 1—figure supplement 1D).
Fixation and brain preparation for MRI
The fixation and preparation of brain specimens for MRI acquisitions is a crucial phase to ensure high quality images and low prevalence of artefacts. The chosen fixative was a 10% formaldehyde buffered solution. Ensuring complete immersion of the brain in the fixative is crucial. To achieve this, a carefully calculated volume of the solution is added to a labeled container (usually around 3 L). The brain is then placed within the container, submerged to guarantee full coverage. Sealing the container prevents contamination. The container remains for 7 days under the fume hood, and we check and gently stir every day to ensure the good repartition of the formaldehyde on the tissue. Once the brain is fixed, it is immersed the brain in a 0.5 L jar filled with PBS for 48 hr before MRI.
1. MRI acquisitions
The diameter of the plastic container was chosen based on the diameter of the MRI antenna used (8.6 cm in diameter).
The sample is placed in a spherical container. The orientation in which the brain is placed (for future reference during the MRI acquisitions) was registered. Aquarium foam squares are placed around the brain to minimize the residual movements from the MRI’s vibrations and to contain the remaining air bubble at the top of the container (Figure 1—figure supplement 2B).
The container is filled to the brim with Fluorinert FC-770, a liquid that optimizes the contrast of the MRI signal and allows the wobble adjustment.
The container is placed in a vacuum chamber (negative pressure of –0.1 Pa.) to limit the presence of air bubbles on the images, for up to 3 hr to remove air bubbles (Shatil et al., 2016; Figure 1—figure supplement 1A). If needed, some Fluorinert FC-770 can be added up to the brim.
The container is sealed with parafilm (Figure 1—figure supplement 2B).
2. Recommended 7T-MRI scanning setup
Place the container with an elevating foam square to contain the remaining bubble at the top of the jar and limit the superimposition of the bubble on the brain (Figure 1—figure supplement 2C and D).
Once in the MRI, it is recommended to perform a sequence of localizer scans with the purpose of: (1) identifying significant distortions caused by air bubbles in the brain or MRI-compatible container, (2) accurately positioning the brain, and (3) establishing the slice positions necessary for subsequent data acquisition (Shatil et al., 2016).
10.7554/eLife.106424.3.sa0eLife AssessmentLerchJason PReviewing EditorUniversity of OxfordUnited KingdomConvincingImportant
This important work compares the size of two brain areas, the amygdala and the hippocampus, across 12 species belonging to the Macaca genus. The authors find, using a convincing methodological approach, that amygdala - but not hippocampal - volume varies with social tolerance grade, with high tolerance species showing larger amygdala than low tolerance species of macaques. Interestingly, their findings also suggest an inverted developmental effect, with intolerant species showing an increase in amygdala volume across the lifespan, compared to tolerant species exhibiting the opposite trend. Overall, this paper offers new insights into the neural basis of social and emotional processing.
This paper investigates the potential link between amygdala volume and social tolerance in multiple macaque species. Through a comparative lens, the authors considered tolerance grade, species, age, sex, and other factors that may contribute to differing brain volumes. They found that amygdala, but not hippocampal, volume differed across tolerance grades such that high-tolerance species showed larger amygdala than low-tolerance species of macaques. They also found that less tolerant species exhibited increases in amygdala volume with age, while more tolerant species showed the opposite. Given their wide range of species with varied biological and ecological factors, the authors' findings provide new, important evidence for changes in amygdala volume in relation to social tolerance grades. Contributions from these findings will greatly benefit future efforts in the field to characterize brain regions critical for social and emotional processing across species.
(1) This study demonstrates a concerted and impressive effort to comparatively examine neuroanatomical contributions to sociality in monkeys. The authors impressively collected samples from 12 macaque species with multiple datapoints across species age, sex, and ecological factors. Species from all four social tolerance grades were present. Further, the age range of the animals is noteworthy, particularly the inclusion of individuals over 20 years old.
(2) This work is the first to report neuroanatomical correlates of social tolerance grade in macaques in one coherent study. Given the prevalence of macaques as a model of social neuroscience, considerations of how socio-cognitive demands are impacted by the amygdala are highly important. The authors' findings will certainly inform future studies on this topic.
(3) The methodology and supplemental figures for acquiring brain MRI images are nicely detailed. Clear information on these parameters is crucial for future comparative interpretations of sociality and brain volume, and the authors do an excellent job of describing this process in full.
(4) The following comments were brought up during the review. In their revision, the authors have sufficiently addressed all of these comments by providing detailed responses and updating their manuscript. First, the revision clarified how much one could draw conclusions about "nature vs. nurture" from this study. Second, the revision also clarified the contributions of very young and very old animals in their correlations. Third, in their revision, the authors expanded on how their results could be interpreted in the context of multiple behavioral traits by Thierry (2021) by providing more detailed descriptions. Finally, during the revision, the authors clarified that both intolerant and tolerant species experience complex socio-cognitive demands and highlighted that socio-cognitive challenges arise across the tolerance spectrum under different behavioral demands.
This comparative study of macaque species and type of social interaction is both ambitious and inevitably comes with a lot of caveats. The overall conclusion is that more intolerant species have a larger amygdala. There are also opposing development profiles regarding amygdala volume depending on whether it is a tolerant or intolerant species.
To achieve any sort of power they have combined data from 4 centres - that have all used different scanning methods and there are some resolution differences. The authors have also had to group species into 4 classifications - again to assist with any generalisations and power. They have focussed on the volumes of two structures, the amygdala and the hippocampus, which seems appropriate. Neither structure is homogeneous and so it may well be that a targeted focus on specific nuclei or subfields would help (the authors may well do this next) - but as the variables would only increase further along with the number of potential comparisons, alongside small group numbers, it seems only prudent to treat these findings are preliminary. That said, it is highly unlikely that large numbers of macaque brains will become available in the near future.
This introduction is by way of saying that the study achieves what it sets out to do, but there are many reasons to see this study as preliminary. The main message seems to be twofold: (1) that more intolerant species have relatively larger amygdalae, and (2) that with development there is an opposite pattern of volume change (increasing with age in intolerant sp and decreasing with age in tolerant species). Finding 1 is the opposite of that predicted in Table 1 - this is fine, but it should be made clearer in the Discussion that this is the case otherwise the reader may feel confused. As I read it, the authors have switched their prediction in the Discussion, which feels uncomfortable.
It is inevitable that the data in a study of this complexity are all too prone to post hoc considerations, to which the authors indulge. I suspect I would end up doing the same but it feels a bit like 'heads I win, tails you lose'. In the case of Grade 1 species, the individuals have a lot to learn especially if they are not top of the hierarchy, but at the same time there are fewer individuals in the troop, making predictions very tricky. As noted above, I am concerned by the seemingly opposite predictions in Table 1 and those in the Discussion regarding tolerance and amygdala volume. (It may be that the predictions in Table 1 are the opposite to how I read them, in which case the Table and preceding text needs to align.)
Comments on revisions:
I am happy with all of the revisions and the care shown by the authors.
In this study, the authors were looking at neurocorrelates of behavioural differences within the genus Macaca. To do so, they engaged in real-world dissection of dead animals (unconnected to the present study) coming from a range of different institutions. They subsequently compare different brain areas, here the amygdala and the hippocampus, across species. Crucially, these species have been sorted according to different levels of social tolerance grades (from 1 to 4). 12 species are represented across 42 individuals. The sampling process has weaknesses ("only half" of the species contained by the genus, and Macaca mulatta, the rhesus macaque, representing 13 of the total number of individuals), but also strengths (the species are decently well represented across the 4 grades) for the given purpose and for the amount of work required here. I will not judge the dissection process as I am not a neuroanatomist, and I will assume that the different interventions do not alter volume in any significant ways / or that the different conditions in which the bodies were kept led to the documented differences across species.
There are two main results of the study. First, in line with their predictions, the authors find that more tolerant macaque species have larger amygdala, compared to the hippocampus that remains undifferentiated across species. Second, they also identify developmental effects, although with different trends: in tolerant species, the amygdala relative volume decreases across the lifespan, while in intolerant species, the contrary occurs. The modifications brought up between the two versions of the article have answered my remarks regarding age/grade/brain area differences.
As such, I think the results are holding strong, but maybe more work is needed with respect to interpretation.
Classification of the social grade, as well as the issue of nature vs nurture have been addressed by the authors, I thank them for this.
I still feel the integration of the amygdala as a common cognitive & emotional center could be possibly more pushed in the discussion, although I acknowledge that it would be complicated to do without knowing how the emotional and social lives of these animals impacted the growth of their amygdala...
Strengths:
Methods & breadth of species tested
Weaknesses:
Interpretations, which, although softened, could still be more integrated with the literature on emotion
10.7554/eLife.106424.3.sa4Author responseSilvereSarahAuthorLaboratoire de Neurosciences Cognitives et AdaptativesStrasbourgFranceLamyJulienAuthorLaboratoire des Sciences de l'Ingénieur, de l'Informatique et de l'ImagerieStrasbourgFrancePoChrystelleAuthorICube, FMTSStrasbourgFranceLegrandMathieuAuthorLaboratoire de Neurosciences Cognitives et AdaptativesStrasbourgFranceSalletJeromeAuthorUniversity of OxfordOxfordUnited KingdomBallestaSebastienAuthorLaboratoire de Neurosciences Cognitives et AdaptativesStrasbourgFrance
The following is the authors’ response to the original reviews.
Public Reviews:
Reviewer #1 (Public review):
We thank Reviewer #1 for its thoughtful and constructive feedback. We found the suggestions particularly helpful in refining the conceptual framework and clarifying key aspects of our interpretations.
Summary:
This paper investigates the potential link between amygdala volume and social tolerance in multiple macaque species. Through a comparative lens, the authors considered tolerance grade, species, age, sex, and other factors that may contribute to differing brain volumes. They found that amygdala, but not hippocampal, volume differed across tolerance grades, such that hightolerance species showed larger amygdala than low-tolerance species of macaques. They also found that less tolerant species exhibited increases in amygdala volume with age, while more tolerant species showed the opposite. Given their wide range of species with varied biological and ecological factors, the authors' findings provide new evidence for changes in amygdala volume in relation to social tolerance grades. Contributions from these findings will greatly benefit future efforts in the field to characterize brain regions critical for social and emotional processing across species.
Strengths:
(1) This study demonstrates a concerted and impressive effort to comparatively examine neuroanatomical contributions to sociality in monkeys. The authors impressively collected samples from 12 macaque species with multiple datapoints across species age, sex, and ecological factors. Species from all four social tolerance grades were present. Further, the age range of the animals is noteworthy, particularly the inclusion of individuals over 20 years old - an age that is rare in the wild but more common in captive settings.
(2) This work is the first to report neuroanatomical correlates of social tolerance grade in macaques in one coherent study. Given the prevalence of macaques as a model of social neuroscience, considerations of how socio-cognitive demands are impacted by the amygdala are highly important. The authors' findings will certainly inform future studies on this topic.
(3) The methodology and supplemental figures for acquiring brain MRI images are well detailed. Clear information on these parameters is crucial for future comparative interpretations of sociality and brain volume, and the authors do an excellent job of describing this process in full.
Weaknesses:
(1) The nature vs. nurture distinction is an important one, but it may be difficult to draw conclusions about "nature" in this case, given that only two data points (from grades 3 and 4) come from animals under one year of age (Method Figure 1D). Most brains were collected after substantial social exposure-typically post age 1 or 1.5-so the data may better reflect developmental changes due to early life experience rather than innate wiring. It might be helpful to frame the findings more clearly in terms of how early experiences shape development over time, rather than as a nature vs. nurture dichotomy.
We agree with the reviewer that presenting our findings through a strict nature vs. nurture dichotomy was potentially misleading. We have revised the introduction and the discussion (e.g. lines 85-95 and 363-365) to clarify that we examined how neurodevelopmental trajectories differ across social grades with the caveat of related to the absence of very young individuals in our samples. We now explicitly mention that our results may reflect both early species-typical biases and experience-dependent maturation.
We positioned our study on social tolerance in a comparative neuroscience framework and introduced a tentative working model that articulates behavioral traits, cognitive dimensions, and their potential subcortical neural substrates
Drawing upon 18 behavioral traits identified in Thierry’s comparative analyses (Thierry, 2021, 2007), we organize these traits into three core dimensions: socio-cognitive demands, behavioral inhibition, and the predictability of the social environment (Table 1). This conceptualization does not aim to redefine social tolerance itself, but rather to provide a structured basis for testing neuroanatomical hypotheses related to social style variability. It echoes recent efforts to bridge behavioral ecology and cognitive neuroscience by linking specific mental abilities – such as executive functions or metacognition – with distinct prefrontal regions shaped by social and ecological pressures (Bouret et al., 2024).
“Cross-fostering experiments (De Waal and Johanowicz, 1993), along with our own results, suggest that social tolerance grades reflect both early, possibly innate predispositions and later environmental shaping”.
(2) It would be valuable to clarify how the older individuals, especially those 20+ years old, may have influenced the observed age-related correlations (e.g., positive in grades 1-2, negative in grades 3-4). Since primates show well-documented signs of aging, some discussion of the potential contribution of advanced age to the results could strengthen the interpretation.
We thank the reviewer for highlighting this important point. In our dataset, younger and older subjects are underrepresented, but they are distributed across all subgroups. Therefore, we do not think that it could drive the interaction effect we are reporting. In our sample, amygdala volume tended to increase with age in intolerant species and decrease in tolerant species. We included a new analysis (Figure 4) that allows providing a clearer assessment of when social grades 1 vs 4 differed in terms of amygdala and hippocampus volume. While our model accounts for age continuously, we agree that age-related variation deserves cautious interpretation and require longitudinal designs in future studies.
We also added the following statements in the discussion (lines 386-391)
“Due to a limited sample size of our study, this crossing trend, already accounted for by our continuous age model, should be further investigated. These results call for cautious interpretation of age-related variation and further emphasize the importance of longitudinal studies integrating both behavioral, cognitive and anatomical data in non-human primates, which would help to better understand the link between social environment and brain development (Song et al., 2021)”.
(3) The authors categorize the behavioral traits previously described in Thierry (2021) into 3 selfdefined cognitive requirements, however, they do not discuss under what conditions specific traits were assigned to categories or justify why these cognitive requirements were chosen. It is not fully clear from Thierry (2021) alone how each trait would align with the authors' categories. Given that these traits/categories are drawn on for their neuroanatomical hypotheses, it is important that the authors clarify this. It would be helpful to include a table with all behavioral traits with their respective categories, and explain their reasoning for selecting each cognitive requirement category.
Thank you for this important suggestion. We have extensively revised the introduction to explain how we derived from the scientific literature the three cognitive dimensions—socio-cognitive demands, behavioral inhibition, and predictability of the social environment—. We now provide a complete overview of the 18 behavioral traits described in Thierry’s framework and their cognitive classification in a dedicated table , along with hypothesized neural correlates. We have also mentioned traits that were not classified in our framework along with short justification of this classification. We believe this addition significantly improves the transparency and intelligibility of our conceptual approach.
“The concept of social tolerance, central to this comparative approach, has sometimes been used in a vague or unidimensional way. As Bernard Thierry (2021) pointed out, the notion was initially constructed around variations in agonistic relationships – dominance, aggressiveness, appeasement or reconciliation behaviors – before being expanded to include affiliative behaviors, allomaternal care or male–male interactions (Thierry, 2021). These traits do not necessarily align along a single hierarchical axis but rather reflect a multidimensional complexity of social style, in which each trait may have co-evolved with others (Thierry, 2021, 2000; Thierry et al., 2004). Moreover, the lack of a standardized scientific definition has sometimes led to labeling species as “tolerant” or “intolerant” without explicit criteria (Gumert and Ho, 2008; Patzelt et al., 2014). These behavioral differences are characterized by different styles of dominance (Balasubramaniam et al., 2012), severity of agonistic interactions (Duboscq et al., 2014), nepotism (Berman and Thierry, 2010; Duboscq et al., 2013; Sueur et al., 2011) and submission signals (De Waal and Luttrell, 1985; Rincon et al., 2023), among the 18 covariant behavioral traits described in Thierry's classification of social tolerance (Thierry, 2021, 2017, 2000)”.
“To ground the investigation of social tolerance in a comparative neuroanatomical framework, we introduce a tentative working model that articulates behavioral traits, cognitive dimensions, and their potential subcortical neural substrates. Drawing upon 18 behavioral traits identified in Thierry’s comparative analyses (Thierry, 2021, 2007), we organized these traits into three core dimensions: socio-cognitive demands, behavioral inhibition, and the predictability of the social environment (Table 1). This conceptualization does not aim to redefine social tolerance itself, but rather to provide a structured basis for testing neuroanatomical hypotheses related to social style variability. It echoes recent efforts to bridge behavioral ecology and cognitive neuroscience by linking specific mental abilities – such as executive functions or metacognition – with distinct prefrontal regions shaped by social and ecological pressures (Bouret et al., 2024; Testard 2022)”.
(4) One of the main distinctions the authors make between high social tolerance species and low tolerance species is the level of complex socio-cognitive demands, with more tolerant species experiencing the highest demands. However, socio-cognitive demands can also be very complex for less tolerant species because they need to strategically balance behaviors in the presence of others. The relationships between socio-cognitive demands and social tolerance grades should be viewed in a more nuanced and context-specific manner.
We fully agree and we did not mean that intolerant species lives in a ‘simple’ social environment but that the ones of more tolerant species is markedly more demanding. Evidence supporting this statement include their more efficient social networks (Sueur et al., 2011) and more complex communicative skills (e.g. tolerant macaques displayed higher levels of vocal diversity and flexibility than intolerant macaques in social situation with high uncertainty Rebout et al., 2020).
In the revised version (lines 106-122), we now highlight that socio-cognitive challenges arise across the tolerance spectrum, including in less tolerant species where strategic navigation of rigid hierarchies and risk-prone interactions is required. We hope that this addition offers a more balanced and nuanced framing of socio-cognitive demands across macaque societies
“The first category, socio-cognitive demands, refers to the cognitive resources needed to process, monitor, and flexibly adapt to complex social environments. Linking those parameters to neurological data is at the core of the social brain theory to explain the expansion of the neocortex in primates (Dunbar). Macaques social systems require advanced abilities in social memory, perspective-taking, and partner evaluation (Freeberg et al., 2012). This is particularly true in tolerant species, where the increased frequency and diversity of interactions may amplify the demands on cognitive tracking and flexibility. Tolerant macaque species typically live in larger groups with high interaction frequencies, low nepotism, and a wider range of affiliative and cooperative behaviors, including reconciliation, coalition-building, and signal flexibility (REF). Tolerant macaque species also exhibit a more diverse and flexible vocal and facial repertoire than intolerants ones which may help reduce ambiguity and facilitate coordination in dense social networks (Rincon et al., 2023; Scopa and Palagi, 2016; Rebout 2020). Experimental studies further show that macaques can use facial expressions to anticipate the likely outcomes of social interactions, suggesting a predictive function of facial signals in managing uncertainty (Micheletta et al., 2012; Waller et al., 2016). Even within less tolerant species, like M. mulatta, individual variation in facial expressivity has been linked to increased centrality in social networks and greater group cohesion, pointing to the adaptive value of expressive signaling across social styles (Whitehouse et al., 2024)”.
(5) While the limitations section touches on species-related considerations, the issue of individual variability within species remains important. Given that amygdala volume can be influenced by factors such as social rank and broader life experience, it might be useful to further emphasize that these factors could introduce meaningful variation across individuals. This doesn't detract from the current findings but highlights the importance of considering life history and context when interpreting subcortical volumes-particularly in future studies.
We have now emphasized this point in the limitations section (lines 441-456). While our current dataset does not allow us to fully control for individual-level variables across all collection centers, we recognize that factors such as rank, social exposure, and individual life history may influence subcortical volumes
“Although we explained some interspecies variability, adding subjects to our database will increase statistical power and will help addressing potential confounding factors such as age or sex in future studies. One will benefit from additional information about each subject. While considered in our modelling, the social living and husbandry conditions of the individuals in our dataset remain poorly documented. The living environment has been considered, and the size of social groups for certain individuals, particularly for individuals from the CdP, have been recorded. However, these social characteristics have not been determined for all individuals in the dataset. As previously stated, the social environment has a significant impact on the volumetry of certain regions. Furthermore, there is a lack of data regarding the hierarchy of the subjects under study and the stress they experience in accordance with their hierarchical rank and predictability of social outcomes position (McCowan et al., 2022)”.
Reviewer #2 (Public review):
We thank Reviewer #2 for its thoughtful remarks and for acknowledging the value of our comparative approach despite its inherent constraints.
Summary:
This comparative study of macaque species and the type of social interaction is both ambitious and inevitably comes with a lot of caveats. The overall conclusion is that more intolerant species have a larger amygdala. There are also opposing development profiles regarding amygdala volume depending on whether it is a tolerant or intolerant species.
To achieve any sort of power, they have combined data from 4 centres, which have all used different scanning methods, and there are some resolution differences. The authors have also had to group species into 4 classifications - again to assist with any generalisations and power. They have focused on the volumes of two structures, the amygdala and the hippocampus, which seems appropriate. Neither structure is homogeneous and so it may well be that a targeted focus on specific nuclei or subfields would help (the authors may well do this next) - but as the variables would only increase further along with the number of potential comparisons, alongside small group numbers, it seems only prudent to treat these findings are preliminary. That said, it is highly unlikely that large numbers of macaque brains will become available in the near future.
This introduction is by way of saying that the study achieves what it sets out to do, but there are many reasons to see this study as preliminary. The main message seems to be twofold: (1) that more intolerant species have relatively larger amygdalae, and (2) that with development, there is an opposite pattern of volume change (increasing with age in intolerant species and decreasing with age in tolerant species). Finding 1 is the opposite of that predicted in Table 1 - this is fine, but it should be made clearer in the Discussion that this is the case, otherwise the reader may feel confused. As I read it, the authors have switched their prediction in the Discussion, which feels uncomfortable.
We thank the reviewer for this important observation. In the original version, Table 1 presented simplified direct predictions linking social tolerance grades to amygdala and hippocampus volumes. We recognize that this formulation may have created confusion In the revised manuscript, we have thoroughly restructured the table and its accompanying rationale. Table 1 now better reflects our conceptual framework grounded in three cognitive dimensions—sociocognitive demands, behavioral inhibition, and social predictability—each linked to behavioral traits and associated neural hypotheses based on published literature. This updated framework, detailed in lines 144-169 of the introduction, provides a more nuanced basis for interpreting our results and avoids the inconsistencies previously noted. The Discussion was also revised accordingly (lines 329-255) to clarify where our findings diverge from the original predictions and to explore alternative explanations based on social complexity. Rather than directly predicting amygdala size from social tolerance grades, we propose that variation in volume emerges from differing combinations of cognitive pressures across species.
It is inevitable that the data in a study of this complexity are all too prone to post hoc considerations, to which the authors indulge. In the case of Grade 1 species, the individuals have a lot to learn, especially if they are not top of the hierarchy, but at the same time, there are fewer individuals in the troop, making predictions very tricky. As noted above, I am concerned by the seemingly opposite predictions in Table 1 and those in the Discussion regarding tolerance and amygdala volume. (It may be that the predictions in Table 1 are the opposite of how I read them, in which case the Table and preceding text need to align.)
In order to facilitate the interpretation of our Bayesian modelling, we have selected a more focused ROI in our automatic segmentation procedure of the Hippocampus (from Hippocampal Formation to Hippocampus) and have added to the new analysis (Figure 4) that helps to properly test whether the hippocampus significantly differs between species from social grade 1 vs 4. The present analysis found that this is the case in adult monkeys. This is therefore consistent with our hypothesis that amygdala volumes are principally explained by heightened sociocognitive demands in more tolerant species.
We also acknowledge the reviewer’s concerns about the limited generalizability due to our sample. The challenges of comparative neuroimaging in non-human primates—especially when using post-mortem datasets—are substantial. Given the ethical constraints and the rarity of available specimens, increasing the number of individuals or species is not feasible in the short term. However, we have made all data and code publicly available and clearly stated the limitations of our sample in the manuscript. Despite these constraints, we believe our dataset offers an unprecedented comparative perspective, particularly due to the inclusion of rare and tolerant species such as M. tonkeana, M. nigra, and M. thibetana, which have never been included in structural MRI studies before. We hope this effort will serve as a foundation for future collaborative initiatives in primate comparative neuroscience.
Reviewer #3 (Public review):
We thank Reviewer #3 for their thoughtful and detailed review. Their comments helped us refine both the conceptual and interpretative aspects of the manuscript. We respond point by point below.
Summary:
In this study, the authors were looking at neurocorrelates of behavioural differences within the genus Macaca. To do so, they engaged in real-world dissection of dead animals (unconnected to the present study) coming from a range of different institutions. They subsequently compare different brain areas, here the amygdala and the hippocampus, across species. Crucially, these species have been sorted according to different levels of social tolerance grades (from 1 to 4). 12 species are represented across 42 individuals. The sampling process has weaknesses ("only half" of the species contained by the genus, and Macaca mulatta, the rhesus macaque, representing 13 of the total number of individuals), but also strengths (the species are decently well represented across the 4 grades) for the given purpose and for the amount of work required here. I will not judge the dissection process as I am not a neuroanatomist, and I will assume that the different interventions do not alter volume in any significant ways / or that the different conditions in which the bodies were kept led to the documented differences across species.
25 brains were extracted by the authors themselves who are highly with this procedure. Overall, we believe that dissection protocols did not alter the total brain volume. Despite our expertise, we experienced some difficulties to not damage the cerebellum. Therefore, this region was not included in our analysis. We also noted that this brain region was also damaged or absent from the Prime-DE dataset.
Several protocols were used to prepare and store tissue. It could have impacted the total brain volume.
We agree that differences in tissue preparation and storage could potentially affect total brain volume. Therefore, we explicitly included the main sample preparation variable — whether brains had been previously frozen — as a covariate in our model. This factor did not explain our results. Moreover, Figures 1D and 1I display the frozen status and its correlation with the amygdala and hippocampus ratios, respectively. Figure 2 shows the parameters of the model and the posterior distributions for the frozen status and total brain volume effects.
There are two main results of the study. First, in line with their predictions, the authors find that more tolerant macaque species have larger amygdala, compared to the hippocampus, which remains undifferentiated across species. Second, they also identify developmental effects, although with different trends: in tolerant species, the amygdala relative volume decreases across the lifespan, while in intolerant species, the contrary occurs. The results look quite strong, although the authors could bring up some more clarity in their replies regarding the data they are working with. From one figure to the other, we switch from model-calculated ratio to modelpredicted volume. Note that if one was to sample a brain at age 20 in all the grades according to the model-predicted volumes, it would not seem that the difference for amygdala would differ much across grades, mostly driven with Grade 1 being smaller (in line with the main result), but then with Grade 2 bigger than Grade 3, and then Grade 4 bigger once again, but not that different from Grade 2.
Overall, despite this, I think the results are pretty strong, the correlations are not to be contested, but I also wonder about their real meaning and implications. This can be seen under 3 possible aspects:
(1) Classification of the social grade
While it may be familiar to readers of Thierry and collaborators, or to researchers of the macaque world, there is no list included of the 18 behavioral traits used to define the three main cognitive requirements (socio-cognitive demands, predictability of the environment, inhibitory control). It would be important to know which of the different traits correspond to what, whether they overlap, and crucially, how they are realized in the 12 study species, as there could be drastic differences from one species to the next. For now, we can only see from Table S1 where the species align to, but it would be a good addition to have them individually matched to, if not the 18 behavioral traits, at least the 3 different broad categories of cognitive requirements.
We fully agree with this observation. In the revised version of the manuscript, we now include a detailed conceptual table listing all 18 behavioral traits from Thierry’s framework. For each trait, we provide its underlying social implications, its associated cognitive dimension (when applicable), and the hypothesized neural correlate.
While some traits may could have been arguably classified in several cognitive dimensions (e.g. reconciliation rate), we preferred to assign each to a unique dimension for clarity. Additionally, the introduction (lines 95-169 + Table1) now explains how each trait was evaluated based on existing literature and assigned to one of the three proposed cognitive categories: socio-cognitive demands, behavioral inhibition, or social unpredictability. This structure offers a clearer and more transparent basis for the neuroanatomical hypotheses tested in the study.
“Navigating social life in primate societies requires substantial cognitive resources: individuals must not only track multiple relationships, but also regulate their own behavior, anticipate others’ reactions, and adapt flexibly to changing social contexts. Taken advantage of databases of magnetic resonance imaging (MRI) structural scans, we conducted the first comparative study integrating neuroanatomical data and social behavioral data from closely related primate species of the same genus to address the following questions: To what extent can differences in volumes of subcortical brain structures be correlated with varying degrees of social tolerance? Additionally, we explored whether these dispositions reflect primarily innate features, shaped by evolutionary processes, or acquired through socialization within more or less tolerant social environments”.
“The first category, socio-cognitive demands, refers to the cognitive resources needed to process, monitor, and flexibly adapt to complex social environments. Linking those parameters to neurological data is at the core of the social brain theory to explain the expansion of the neocortex in primates (Dunbar). Macaques social systems require advanced abilities in social memory, perspective-taking, and partner evaluation (Freeberg et al., 2012). This is particularly true in tolerant species, where the increased frequency and diversity of interactions may amplify the demands on cognitive tracking and flexibility. Tolerant macaque species typically live in larger groups with high interaction frequencies, low nepotism, and a wider range of affiliative and cooperative behaviors, including reconciliation, coalition-building, and signal flexibility (REF). Tolerant macaque species also exhibit a more diverse and flexible vocal and facial repertoire than intolerants ones which may help reduce ambiguity and facilitate coordination in dense social networks (Rincon et al., 2023; Scopa and Palagi, 2016; Rebout 2020). Experimental studies further show that macaques can use facial expressions to anticipate the likely outcomes of social interactions, suggesting a predictive function of facial signals in managing uncertainty (Micheletta et al., 2012; Waller et al., 2016). Even within less tolerant species, like M. mulatta, individual variation in facial expressivity has been linked to increased centrality in social networks and greater group cohesion, pointing to the adaptive value of expressive signaling across social styles (Whitehouse et al., 2024)”.
“The second category, inhibitory control, includes traits that involve regulating impulsivity, aggression, or inappropriate responses during social interactions. Tolerant macaques have been shown to perform better in tasks requiring behavioral inhibition and also express lower aggression and emotional reactivity in both experimental and natural contexts (Joly et al., 2017; Loyant et al., 2023). These features point to stronger self-regulation capacities in species with egalitarian or less rigid hierarchies. More broadly, inhibition – especially in its strategic form (self-control) – has been proposed to play a key role in the cohesion of stable social groups. Comparative analyses across mammals suggest that this capacity has evolved primarily in anthropoid primates, where social bonds require individuals to suppress immediate impulses in favour of longer-term group stability (Dunbar and Shultz, 2025). This view echoes the conjecture of Passingham and Wise (2012), who proposed that the emergence of prefrontal area BA10 in anthropoids enabled the kind of behavioural flexibility needed to navigate complex social environments (Passingham et al., 2012)”.
“The third category, social environment predictability, reflects how structured and foreseeable social interactions are within a given society. In tolerant species, social interactions are more fluid and less kin-biased, leading to greater contextual variation and role flexibility, which likely imply a sustained level of social awareness. In fact, as suggested by recent research, such social uncertainty and prolonged incentives are reflected by stress-related physiology : tolerant macaques such as M. tonkeana display higher basal cortisol levels, which may be indicative of a chronic mobilization of attentional and regulatory resources to navigate less predictable social environments (Sadoughi et al., 2021)”.
“Each behavioral trait was individually evaluated based on existing empirical literature regarding the types of cognitive operations it likely involves. When a primary cognitive dimension could be identified, the trait was assigned accordingly. However, some behaviors – such as maternal protection, allomaternal care, or delayed male dispersal – do not map neatly onto a single cognitive process. These traits likely emerge from complex configurations of affective and socialmotivational systems, and may be better understood through frameworks such as attachment theory (Suomi, 2008), which emphasizes the integration of social bonding, emotional regulation, and contextual plasticity. While these dimensions fall beyond the scope of the present framework, they offer promising directions for future research, particularly in relation to the hypothalamic and limbic substrates of social and reproductive behavior”.
“Rather than forcing these traits into potentially misleading categories, we chose to leave them unclassified within our current cognitive framework. This decision reflects both a commitment to conceptual clarity and the recognition that some behaviors emerge from a convergence of cognitive demands that cannot be neatly isolated. This tripartite framework, leaving aside reproductive-related traits, provides a structured lens through which to link behavioral diversity to specific cognitive processes and generate neuroanatomical predictions”.
(2) Issue of nature vs nurture
Another way to look at the debate between nature vs nurture is to look at phylogeny. For now, there is no phylogenetic tree that shows where the different grades are realized. For example, it would be illuminating to know whether more related species, independently of grades, have similar amygdala or hippocampus sizes. Then the question will go to the details, and whether the grades are realized in particular phylogenetic subdivisions. This would go in line with the general point of the authors that there could be general species differences.
As pointed out by Thierry and collaborators, the social tolerance concept is already grounded in a phylogenetic framework as social tolerance matches the phylogenetical tree of these macaque species, suggesting a biological ground of these behavioral observations. Given the modest sample size and uneven species representation, we opted not to adopt tools such as Phylogenetic Generalized Least Squares (PGLS) in our analysis. Our primary aim in this study was to explore neuroanatomical variation as a function of social traits, not to perform a phylogenetic comparative analysis per see. That said, we now explicitly acknowledge this limitation in the Discussion and indicate that future work using larger datasets and phylogenetic methods will be essential to disentangle social effects from evolutionary relatedness. We hope that making our dataset openly available will facilitate such futures analyses.
With respect to nurture, it is likely more complicated: one needs to take into account the idiosyncrasies of the life of the individual. For example, some of the cited literature in humans or macaques suggests that the bigger the social network, the bigger the brain structure considered. Right, but this finding is at the individual level with a documented life history. Do we have any of this information for any of the individuals considered (this is likely out of the scope of this paper to look at this, especially for individuals that did not originate from CdP)?
We appreciate this insightful observation. Indeed, findings from studies in humans and nonhuman primates showing associations between brain structure and social network size typically rely on detailed life history and behavioral data at the individual level. Unfortunately, such finegrained information was not consistently available across our entire sample. While some individuals from the Centre de Primatologie (CdP) were housed in known group compositions and social settings, we did not have access to longitudinal social data—such as rank, grooming rates, or network centrality—that would allow for robust individual-level analyses. We now acknowledge this limitation more clearly in the Discussion (lines 436-443), and we fully agree that future work combining neuroimaging with systematic behavioral monitoring will be necessary to explore how species-level effects interact with individual social experience.
(3) Issue of the discussion of the amygdala's function
The entire discussion/goal of the paper, states that the amygdala is connected to social life. Yet, before being a "social center", the amygdala has been connected to the emotional life of humans and non-humans alike. The authors state L333/34 that "These findings challenge conventional expectations of the amygdala's primary involvement in emotional processes and highlight the complexity of the amygdala's role in social cognition". First, there is no dichotomy between social cognition and emotion. Emotion is part of social cognition (unless we and macaques are robots). Second, there is nowhere in the paper a demonstration that the differences highlighted here are connected to social cognition differences per se. For example, the authors have not tested, say, if grade 4 species are more afraid of snakes than grade 1 species. If so, one could predict they would also have a bigger amygdala, and they would probably also find it in the model. My point is not that the authors should try to correlate any kind of potential aspect that has been connected to the amygdala in the literature with their data (see for example the nice review by DomínguezBorràs and Vuilleumier, https://doi.org/10.1016/B978-0-12-823493-8.00015-8), but they should refrain from saying they have challenged a particular aspect if they have not even tested it. I would rather engage the authors to try and discuss the amygdala as a multipurpose center, that includes social cognition and emotion.
We thank the reviewer for this important and nuanced point. We have revised the manuscript to adopt a more cautious and integrative tone regarding the function of the amygdala. In the revised Discussion (lines 341-355), we now explicitly state that the amygdala is involved in a broad range of processes—emotional, social, and affective—and that these domains are deeply intertwined. Rather than proposing a strict dissociation, we now suggest that the amygdala supports integrated socio-emotional functions that are mobilized differently across social tolerance styles. We also cite recent relevant literature (e.g., Domínguez-Borràs & Vuilleumier, 2021) to support this view and have removed any claim suggesting we challenge the emotional function of the amygdala per se. Our aim is to contribute to a richer understanding of how affective and social processes co-construct structural variation in this region.
Strengths:
Methods & breadth of species tested.
Weaknesses:
Interpretation, which can be described as 'oriented' and should rather offer additional views.
Recommendations for the authors:
Reviewer #1 (Recommendations for the authors):
Private Comments:
(1) Table 1 should be formatted for clarity i.e., bolded table headers, text realignment, and spacing. It was not clear at first glance how information was organized. It may also be helpful to place behavioral traits as the first column, seeing that these traits feed into the author's defined cognitive requirements.
We have reformatted Table 1 to improve clarity and readability. Behavioral traits now appear in the first column, followed by cognitive dimensions and hypothesized neural correlates. Column headers have been bolded and alignment has been standardized.
(2) Figures could include more detail to help with interpretations. For example, Figure 3 should define values included on the x-axis in the figure caption, and Figure 4 should explain the use of line, light color, and dark color. Figure 1 does not have a y-axis title.
The figures have been revised and legends completed to ensure more clarity.
(3) Please proofread for typos throughout.
The manuscript has been carefully proofread, and all typographical and grammatical errors have been corrected. These changes are visible in the tracked version.
Reviewer #2 (Recommendations for the authors):
Specific comments:
(1) Given all of the variability would it not be a good idea to just compare (eg in the supplemental) the macaque data from just the Strasbourg centre for m mulatta and m toneanna. I appreciate the ns will be lower, but other matters are more standardized.
We fully understand the reviewer’s suggestion to restrict the comparison to data collected at a single site in order to minimize inter-site variability. However, as noted, such an analysis would come at the cost of statistical power, as the number of individuals per species within a single center is small. For example, while M. tonkeana is well represented at the Strasbourg centre, only one individual of M. mulatta is available from the same site. Thus, a restricted comparison would severely limit the interpretability of results, particularly for age-related trajectories. To address variability, we included acquisition site and brain preservation method as covariates or predictors where appropriate, and we have been cautious in our interpretations. We also now emphasize in the Methods and Discussion the value of future datasets with more standardized acquisition protocols across species and centers. We hope that by openly sharing our data and workflow, we can contribute to this broader goal.
(2) I have various minor edits:
(a) L 25 abstract - Specify what is meant by 'opposite trend'; the reader cannot infer what this is.
Modified in line 25-28: “Unexpectedly, tolerant species exhibited a decrease in relative amygdala volume across the lifespan, contrasting with the age-related increase observed in intolerant species—a developmental pattern previously undescribed in primates.”
(b) L67 - The reference 'Manyprimates' needs fixing as it does in the references section.
After double checking, Manyprimates studies are international collaborative efforts that are supposed to be cite this way (https://manyprimates.github.io/#pubs).
(c) L74 - Taking not Taken.
This typo has been corrected.
(d) L129 - It says 'total volume', but this is corrected total volume?
We have clarified in the figures legends that the “total brain volume” used in our analyses excludes the cerebellum and the myelencephalon, as specified in our image preprocessing protocol. This ensures consistency across individuals and institutions.
(e) L138 - Suddenly mentions 'frozen condition' without any prior explanation - this needs explaining in the legend - also L144.
We have added an explanation of the ‘frozen condition’ variable in in the relevant figure legend.
(f) L166 - Results - it would be helpful to remind readers what Grade 1 signifies, ie intolerant species.
We now include a brief reminder in the Results section that Grade 1 corresponds to socially intolerant species, to help readers unfamiliar with the classification (Lines 240-251).
(g)Figure 4 - Provide the ns for each of the 4 grades to help appreciate the meaningfulness of the curves, etc.
The number of subjects has been added to the Figure and a novel analysis helps in the revised ms help to appreciate the meaningfulness of some of these curves.
(h) L235 - 'we had assumed that species of high social tolerance grade would have presented a smaller amygdala in size compared to grade 1'. But surely this is the exact opposite of what is predicted in Table 1 - ie, the authors did not predict this as I read the paper (Unless Table l is misleading/ambiguous and needs clarification).
As discussed in our response to Reviewer #2 and #3, we have restructured both Table 1 and the Discussion to ensure consistency. We now explicitly state that the findings diverge from our initial inhibitory-control-based prediction and propose alternative interpretations based on sociocognitive demands.
(i) L270 - 'This observation' which?? Specify.
We have replaced ‘this observation’ with a precise reference to the observed developmental decrease in amygdala volume in tolerant species.
(j) L327 - 'groundbreaking' is just hype given that there are so many caveats - I personally do not like the word - novel is good enough.
We have replaced the word ‘groundbreaking’ with ‘novel’ to adopt a more measured and appropriate tone in the discussion.
(3) I might add that I am happy with the ethics regarding this study.
Thanks, we are also happy that we were able to study macaque brains from different species using opportunistic samplings along with already available data. We are collectively making progress on this!
(4) Finally, I should commend the authors on all the additional information that they provide re gender/age/species. Given that there are 2xs are many females as males, it would be good to know if this affects the findings. I am not a primatologist, so I don't know, for example, if the females in Grade 1 monkeys are just as intolerant as the males?
We thank the reviewer for this thoughtful comment. We now explicitly mention the female-biased sex ratio in the Methods section and report in the Results (Figure 2, Figure 3) that sex was included as a covariate in our Bayesian models. While a small effect of sex was found for hippocampal volume, no effect was observed for the amygdala. Given the strong imbalance in our dataset (2:1 female-to-male ratio), we refrained from drawing any conclusion about sex-specific patterns, as these would require larger and more balanced samples. Although we did not test for sex-by-grade interactions, we agree that this question—especially regarding whether females and males express social style differences similarly across grades—represents an important direction for future comparative work.
Reviewer #3 (Recommendations for the authors):
I found the article well-written, and very easy to follow, so I have little ways to propose improvements to the article to the authors, besides addressing the various major points when it comes to interpretation of the data.
One list I found myself wanting was in fact the list of the social tolerance grades, and the process by which they got selected into 3 main bags of socio-cognitive skills. Then it would become interesting to see how each of the 12 species compares within both the 18 grades (maybe once again out of the scope of this paper, there are likely reviews out there that already do that, but then the authors should explicitly mention so in the paper: X, 19XX have compared 15 out of 18 traits in YY number of macaque species); and within the 3 major subcognitive requirements delineated by the authors, maybe as an annex?
We thank the reviewer for this thoughtful suggestion. In the revised manuscript, we now include a detailed table (Table 1) that lists the 18 behavioral traits derived from Thierry’s framework, along with their associated cognitive dimension and hypothesized neuroanatomical correlate. While we did not create a matrix mapping each of the 12 species across all 18 traits due to space and data availability constraints, we agree this is an important direction that should be tackled by primatologist. We now include a sentence (line 87-90) in the manuscript to guide readers to previous comparative reviews (e.g., Thierry, 2000; Thierry et al., 2004, 2021) that document the expression of these traits across macaque species. We also clarify that our three cognitive categories are conceptual tools intended to structure neuroanatomical predictions, and not formal clusters derived from quantitative analyses.
In the annex, it would also be good to have a general summarizing excel/R file for the raw data, with important information like age, sex, and the relevant calculated volumes for each individual. The folders available following the links do not make it an easy task for a reader to find the raw data in one place.
We fully agree with the reviewer on the importance of data accessibility. We have now uploaded an additional supplementary file in .csv format on our OSF repository, which includes individuallevel metadata for all 42 macaques: species, sex, age, social grade, total brain volume, amygdala volume, and hippocampus volume. The link to this file is now explicitly mentioned in the Data Availability section. We hope this will facilitate comparisons with other datasets and improve usability for the community. In addition, we provide in a supplementary table the raw data that were used for our Bayesian modelling (see below).
The availability of the raw data would also clear up one issue, which I believe results from the modelling process: it looks odd on Figure 2, that volume ratios, defined as the given brain area volume divided by the total brain volume, give values above 1 (especially for the hippocampus). As such, the authors should either modify the legend or the figure. In general, it would be nicer to have the "real values" somewhere easily accessible, so that they can be compared more broadly with: (1) other macaques species to address questions relevant to the species; (2) other primates to address other questions that are surely going to arise from this very interesting work!
We thank the reviewer for pointing this out. The ratio values in Figure 1 correspond to the proportion of the regional volume (amygdala or hippocampus) relative to the total brain volume, excluding the cerebellum and myelencephalon. As such, values above 0.01 (i.e., above 1% of the brain volume) are expected for these structures and do not indicate an error. We have updated the figure legend to clarify this point explicitly. In addition, we have now made a cleaned .csv file available via OSF, containing all raw volumetric data and metadata in a format that facilitates cross-species or cross-study comparisons. This replaces the previous folder-based structure, which may have been less accessible.
Typos:
L233: delete 'in'
L430: insert space in 'NMT template(Jung et al., 2021).'