Virtual social grooming in macaques and its psychophysiological effects.

Allogrooming is a widespread, pervasive activity among non-human primates. Besides its hygienic function, it is thought to be instrumental in maintaining social bonds and establishing hierarchical structures within groups. However, the question arises as to whether the physiological and social benefits derived from social touch stem directly from body stimulation, or whether other mechanisms come into play. We address this question by analyzing an elaborate social behavior that we observed in two adult male macaques. This behavior demonstrates the existence of a persistent motivation to interact through a form of simulated grooming, as the animals were housed in adjacent enclosures separated by a glass panel preventing direct tactile contact. We find that such virtual grooming produces similar physiological sensations and social effects as allogrooming. We suggest that this behavior engages affective and reward brain circuits to the same extent as real social touch, and that this is probably achieved through high level processes similar to those involved in bodily illusions or synaesthetic phenomena previously described in humans. This observation reveals the unsuspected capacity of non-human primates to invent alternative, quasi-symbolic strategies to obtain effects similar to those provided by direct bodily interaction, which are so important for maintaining social bonds.

Distinct neural adaptations to time demand in the striatum and the hippocampus.

How do neural codes adjust to track time across a range of resolutions, from milliseconds to multi-seconds, as a function of the temporal frequency at which events occur? To address this question, we studied time-modulated cells in the striatum and the hippocampus, while macaques categorized three nested intervals within the sub-second or the supra-second range (up to 1, 2, 4, or 8 s), thereby modifying the temporal resolution needed to solve the task. Time-modulated cells carried more information for intervals with explicit timing demand, than for any other interval. The striatum, particularly the caudate, supported the most accurate temporal prediction throughout all time ranges. Strikingly, its temporal readout adjusted non-linearly to the time range, suggesting that the striatal resolution shifted from a precise millisecond to a coarse multi-second range as a function of demand. This is in line with monkey's behavioral latencies, which indicated that they tracked time until 2 s but employed a coarse categorization strategy for durations beyond. By contrast, the hippocampus discriminated only the beginning from the end of intervals, regardless of the range. We propose that the hippocampus may provide an overall poor signal marking an event's beginning, whereas the striatum optimizes neural resources to process time throughout an interval adapting to the ongoing timing necessity.

Assessing the allocation of attention during visual search using digit-tracking, a calibration-free alternative to eye tracking.

Digit-tracking, a simple, calibration-free technique, has proven to be a good alternative to eye tracking in vision science. Participants view stimuli superimposed by Gaussian blur on a touchscreen interface and slide a finger across the display to locally sharpen an area the size of the foveal region just at the finger's position. Finger movements are recorded as an indicator of eye movements and attentional focus. Because of its simplicity and portability, this system has many potential applications in basic and applied research. Here we used digit-tracking to investigate visual search and replicated several known effects observed using different types of search arrays. Exploration patterns measured with digit-tracking during visual search of natural scenes were comparable to those previously reported for eye-tracking and constrained by similar saliency. Therefore, our results provide further evidence for the validity and relevance of digit-tracking for basic and applied research on vision and attention.

Culture-free perceptual invariant for trustworthiness.

Humans beings decide to trust others selectively, often based on the appearance of a face. But how do observers deal with the wide variety of facial morphologies and, in particular, those outside their own familiar cultural group? Using reverse correlation, a data-driven approach to explore how individuals create internal representations without external biases, we studied the generation of trustworthy faces by French and Chinese participants (N = 160) within and outside their own cultural group. Participants selected the most trustworthy or attractive (control condition) face from two identical European or Asian descent faces that had been modified by different noise masks. A conjunction analysis to reveal facial features common to both cultures showed that Chinese and French participants unconsciously increased the contrast of the "pupil-iris area" to make the face appear more trustworthy. No significant effects common to both groups were found for the attraction condition suggesting that attraction judgements are dependent on cultural processes. These results suggest the presence of universal cross-cultural mechanisms for the construction of implicit first impressions of trust, and highlight the importance of the eyes area in this process.

Two functions of the primate amygdala in social gaze.

Appropriate gaze interaction is essential for primate social life. Prior studies have suggested the involvement of the amygdala in processing eye cues but its role in gaze behavior during live social exchanges remains unknown. We recorded the activity of neurons in the amygdala of two monkeys as they engaged in spontaneous visual interactions. We showed that monkeys adjust their oculomotor behavior and actively seek to interact with each other through mutual gaze. During fixations on the eye region, some amygdala neurons responded with short latency and more strongly to mutual than non-reciprocal gaze (averted gaze). Other neurons responded with long latency and were more strongly modulated by active, self-terminated mutual gaze fixations than by passively terminated ones. These results suggest that the amygdala not only participates to the evaluation of eye contact, but also plays a role in the timing of fixations which is crucial for adaptive social interactions through gaze.

Following the gold trail: Reward influences on spatial exploration in neglect.

Spatial attention is guided by the perceived salience and relevance of objects in the environment, a process considered to depend on a broad parieto-frontal cortical network. Signals arising from the limbic and nigrostriatal pathways conveying affective and motivational cues are also known to modulate visual selection, but the nature of this contribution and its relation to spatial attention remain unclear. We investigated the role of reward information in 15 patients with left hemispatial neglect and 15 control subjects playing multiple rounds of a virtual foraging game. Participants' exploration tracked dynamically adjusted underlying reward distributions, largely unbeknownst to them. Both control and neglect participants showed typical exploration/exploitation balance, dependent on abundance or scarcity of rewards. De-reinforcing previously favored, mostly right, regions of space attenuated left space under-exploration in patients. Multiple regression analysis indicates that such reward-based training may benefit mostly patients early after lesion onset, with mild neglect and small lesions sparing subcortical regions. Our findings support the view that spatial exploration recruits heavily right hemispheric visuospatial attentional mechanisms as well as reward signals processed by basal ganglia and prefrontal cortical circuits, which serve to learn about the motivational relevance of environmental stimuli and help prioritize attention and motor response selection.

The role of the posterior parietal cortex in saccadic error processing.

Ocular saccades rapidly displace the fovea from one point of interest to another, thus minimizing the loss of visual information and ensuring the seamless continuity of visual perception. However, because of intrinsic variability in sensory-motor processing, saccades often miss their intended target, necessitating a secondary corrective saccade. Behavioral evidence suggests that the oculomotor system estimates saccadic error by relying on two sources of information: the retinal feedback obtained post-saccadically and an internal extra-retinal signal obtained from efference copy or proprioception. However, the neurophysiological mechanisms underlying this process remain elusive. We trained two rhesus monkeys to perform visually guided saccades towards a target that was imperceptibly displaced at saccade onset on some trials. We recorded activity from neurons in the lateral intraparietal area (LIP), an area implicated in visual, attentional and saccadic processing. We found that a subpopulation of neurons detect saccadic motor error by firing more strongly after an inaccurate saccade. This signal did not depend on retinal feedback or on the execution of a secondary corrective saccade. Moreover, inactivating LIP led to a large and selective increase in the latency of small (i.e., natural) corrective saccade initiation. Our results indicate a key role for LIP in saccadic error processing.

Digit-tracking as a new tactile interface for visual perception analysis.

Eye-tracking is a valuable tool in cognitive science for measuring how visual processing resources are allocated during scene exploration. However, eye-tracking technology is largely confined to laboratory-based settings, making it difficult to apply to large-scale studies. Here, we introduce a biologically-inspired solution that involves presenting, on a touch-sensitive interface, a Gaussian-blurred image that is locally unblurred by sliding a finger over the display. Thus, the user's finger movements provide a proxy for their eye movements and attention. We validated the method by showing strong correlations between attention maps obtained using finger-tracking vs. conventional optical eye-tracking. Using neural networks trained to predict empirically-derived attention maps, we established that identical high-level features hierarchically drive explorations with either method. Finally, the diagnostic value of digit-tracking was tested in autistic and brain-damaged patients. Rapid yet robust measures afforded by this method open the way to large scale applications in research and clinical settings.

Short-Term Reciprocity in Macaque's Social Decision-Making.

Primates live in complex social environments, where individuals create meaningful networks by adapting their behavior according to past experiences with others. Although free-ranging primates do show signs of reciprocity, experiments in more controlled environments have mainly failed to reproduce such social dynamics. Hence, the cognitive and neural processes allowing monkeys to reciprocate during social exchanges remains elusive. Here, pairs of long-tailed macaques (Macaca fascicularis) took turns into a social decision task involving the delivery of positive (juice reward) or negative (airpuff) outcomes. By analyzing the contingencies of one partner's past decisions on the other's future decisions, we demonstrate the presence of reciprocity, but only for the exchange of negative outcomes. Importantly, to display this decisional bias, the monkey needs to witness its partner's decisions, since non-social deliveries of the same outcome did not have such effect. Withholding of negative outcomes also predicted future social decisions, which suggest that the observed tit-for-tat strategy may not only be motivated by retaliation after receiving an airpuff but also by the gratefulness of not having received one. These results clarify the apparent dichotomy within the scientific literature of reciprocity in non-human primates and suggest that their social cognition comprise revenge and gratitude.

Face cells in orbitofrontal cortex represent social categories.

Perceiving social and emotional information from faces is a critical primate skill. For this purpose, primates evolved dedicated cortical architecture, especially in occipitotemporal areas, utilizing face-selective cells. Less understood face-selective neurons are present in the orbitofrontal cortex (OFC) and are our object of study. We examined 179 face-selective cells in the lateral sulcus of the OFC by characterizing their responses to a rich set of photographs of conspecific faces varying in age, gender, and facial expression. Principal component analysis and unsupervised cluster analysis of stimulus space both revealed that face cells encode face dimensions for social categories and emotions. Categories represented strongly were facial expressions (grin and threat versus lip smack), juvenile, and female monkeys. Cluster analyses of a control population of nearby cells lacking face selectivity did not categorize face stimuli in a meaningful way, suggesting that only face-selective cells directly support face categorization in OFC. Time course analyses of face cell activity from stimulus onset showed that faces were discriminated from nonfaces early, followed by within-face categorization for social and emotion content (i.e., young and facial expression). Face cells revealed no response to acoustic stimuli such as vocalizations and were poorly modulated by vocalizations added to faces. Neuronal responses remained stable when paired with positive or negative reinforcement, implying that face cells encode social information but not learned reward value associated to faces. Overall, our results shed light on a substantial role of the OFC in the characterizations of facial information bearing on social and emotional behavior.

Selective Inhibition of Volitional Hand Movements after Stimulation of the Dorsoposterior Parietal Cortex in Humans.

Inhibition is a central component of motor control. Although current models emphasize the involvement of frontal networks [1, 2], indirect evidence suggests a potential contribution of the posterior parietal cortex (PPC). This region is active during inhibition of upper-limb movements to undesired targets [3], and its stimulation with single magnetic pulses can depress motor-evoked potentials [4, 5]. Also, it has been speculated that alien hand movements caused by focal parietal lesions reflect a release of inhibition from PPC to M1 [6]. Considering these observations, we instructed 16 patients undergoing awake brain surgery to perform continuous hand movements while electrical stimulation was applied over PPC. Within a restricted dorsoposterior area, we identified focal sites where stimulation prevented movement initiation and instantly inhibited ongoing responses (which restarted promptly at stimulation offset). Inhibition was selective of the instructed response. It did not affect speech, hand movements passively generated through muscle electrical stimulation, or the ability to initiate spontaneous actions with other body segments (e.g., the feet). When a patient inadvertently performed a bilateral movement, a bilateral inhibition was found. When asked to produce unilateral movements, this patient presented a contralesional but not ipsilateral inhibition. This selectivity contrasted sharply with the unspecific inhibitions reported by previous studies within frontal regions, where speech and all limbs are typically affected (as we here confirm in a subset of patients) [7-10]. These results provide direct evidence that a specific area in the dorsoposterior parietal cortex can inhibit volitional upper-limb responses with high selectivity.

Implicit preference for human trustworthy faces in macaque monkeys.

It has been shown that human judgements of trustworthiness are based on subtle processing of specific facial features. However, it is not known if this ability is a specifically human function, or whether it is shared among primates. Here we report that macaque monkeys (Macaca Mulatta and Macaca Fascicularis), like humans, display a preferential attention to trustworthiness-associated facial cues in computer-generated human faces. Monkeys looked significantly longer at faces categorized a priori as trustworthy compared to untrustworthy. In addition, spatial sequential analysis of monkeys' initial saccades revealed an upward shift with attention moving to the eye region for trustworthy faces while no change was observed for the untrustworthy ones. Finally, we found significant correlations between facial width-to-height ratio- a morphometric feature that predicts trustworthiness' judgments in humans - and looking time in both species. These findings suggest the presence of common mechanisms among primates for first impression of trustworthiness.

A comparison of methods to measure central and peripheral oxytocin concentrations in human and non-human primates.

Oxytocin (OT) concentration in the blood is considered to be a marker of its action in the brain. However, two problems have emerged when measuring OT level in the blood. First, it is unclear whether different methods of assessment lead to similar OT values. Second, it is unclear if plasma OT concentrations is informative on what OT does in the brain. To clarify these issues, we collected cerebrospinal fluid (CSF) from the brain ventricle of 25 patients during surgery to compare with plasma OT after simultaneous blood withdrawal. Additionally, we collected 12 CSF and blood samples from non-human primates while awake or under anaesthesia. We used four methods to assay OT concentrations: Commercial EIA with/without extraction, laboratory developed EIA with filtration and RIA with extraction. Three of these methods showed a positive correlation between plasma and CSF OT, suggesting a link between plasma and central OT, at least under specific testing conditions. However, none of the methods correlated to each other. Our results show major disagreements among methods used here to measure peripheral and brain OT and therefore they call for more caution when plasma OT is taken as a marker of central OT.

Oxytocin and Serotonin Brain Mechanisms in the Nonhuman Primate.

Oxytocin (OT) is increasingly studied for its therapeutic potential in psychiatric disorders, which are associated with the deregulation of several neurotransmission systems. Studies in rodents demonstrated that the interaction between OT and serotonin (5-HT) is critical for several aspects of social behavior. Using PET scan in humans, we have recently found that 5-HT 1A receptor (5-HT1AR) function is modified after intranasal oxytocin intake. However, the underlying mechanism between OT and 5-HT remains unclear. To understand this interaction, we tested 3 male macaque monkeys using both [11C]DASB and [18F]MPPF, two PET radiotracers, marking the serotonin transporter and the 5-HT1AR, respectively. Oxytocin (1 IU in 20 µl of ACSF) or placebo was injected into the brain lateral ventricle 45 min before scans. Additionally, we performed postmortem autoradiography. Compared with placebo, OT significantly reduced [11C]DASB binding potential in right amygdala, insula, and hippocampus, whereas [18F]MPPF binding potential increased in right amygdala and insula. Autoradiography revealed that [11C]DASB was sensitive to physiological levels of 5-HT modification, and that OT does not act directly on the 5-HT1AR. Our results show that oxytocin administration in nonhuman primates influences serotoninergic neurotransmission via at least two ways: (1) by provoking a release of serotonin in key limbic regions; and (2) by increasing the availability of 5-HT1AR receptors in the same limbic areas. Because these two molecules are important for social behavior, our study sheds light on the specific nature of their interaction, therefore helping to develop new mechanisms-based therapies for psychiatric disorders.SIGNIFICANCE STATEMENT Social behavior is largely controlled by brain neuromodulators, such as oxytocin and serotonin. While these are currently targeted in the context of psychiatric disorders such as autism and schizophrenia, a new promising pharmaceutical strategy is to study the interaction between these systems. Here we depict the interplay between oxytocin and serotonin in the nonhuman primate brain. We found that oxytocin provokes the release of serotonin, which in turn impacts on the serotonin 1A receptor system, by modulating its availability. This happens in several key brain regions for social behavior, such as the amygdala and insula. This novel finding can open ways to advance treatments where drugs are combined to influence several neurotransmission networks.

Gaze-informed, task-situated representation of space in primate hippocampus during virtual navigation.

To elucidate how gaze informs the construction of mental space during wayfinding in visual species like primates, we jointly examined navigation behavior, visual exploration, and hippocampal activity as macaque monkeys searched a virtual reality maze for a reward. Cells sensitive to place also responded to one or more variables like head direction, point of gaze, or task context. Many cells fired at the sight (and in anticipation) of a single landmark in a viewpoint- or task-dependent manner, simultaneously encoding the animal's logical situation within a set of actions leading to the goal. Overall, hippocampal activity was best fit by a fine-grained state space comprising current position, view, and action contexts. Our findings indicate that counterparts of rodent place cells in primates embody multidimensional, task-situated knowledge pertaining to the target of gaze, therein supporting self-awareness in the construction of space.

Reward and decision processes in the brains of humans and nonhuman primates.

Choice behavior requires weighing multiple decision variables, such as utility, uncertainty, delay, or effort, that combine to define a subjective value for each considered option or course of action. This capacity is based on prior learning about potential rewards (and punishments) that result from prior actions. When made in a social context, decisions can involve strategic thinking about the intentions of others and about the impact of others' behavior on one's own outcome. Valuation is also influenced by different emotions that serve to adaptively regulate our choices in order to, for example, stay away from excessively risky gambles, prevent future regrets, or avoid personal rejection or conflicts. Drawing on economic theory and on advances in the study of neuronal mechanisms, we review relevant recent experiments in nonhuman primates and clinical observations made in neurologically impaired patients suffering from impaired decision-making capacities.

La conducta de elección requiere sopesar múltiples variables de decisión, como la utilidad, la incertidumbre, el retraso o el esfuerzo que se combinan para definir un valor subjetivo para cada opción o curso de acción que se considere. Esta capacidad está basada en el aprendizaje previo acerca de las potencia les recompensas (y castigos) que resultan de las acciones anteriores. Cuando las decisiones se realizan en un contexto social pueden involucrar un pensamiento estratégico acerca de las intenciones de otros y acerca del impacto de las conductas de otros en el propio resultado de uno. La valoración también está influenciada por diferentes emociones que sirven para regular adaptativamente nuestras electiones con el fin de, por ejemplo, alejarse de juegos ex-cesivamente riesgosos, prevenir futuras lamentaciones o evitar rechazo o conflictos personales. Basándose en la teoría económica y en los avances en el estudio de los mecanismos neurales, se revisan experimentos relevantes recientes en primates no humanos y observaciones clínicas realizadas en pacientes deteriorados neurológicamente quienes tienen alteraciones en la capacidad de tomar decisiones.

Choisir nécessite de soupeser plusieurs variables de décision, comme l'utilité, l'incertitude, l'attente ou l'effort, qui se combinent pour définir une valeur subjective pour chaque option envisagée ou pour chaque plan d'action. Cette aptitude se fonde sur les expériences d'apprentissage lors des récompenses (et punitions) potentielles résultant d'actes antérieurs. Prises dans un contexte social, les décisions peuvent impliquer une pensée stratégique sur les intentions de l'autre et sur le rôle du comportement de l'autre sur notre propre choix. L'estimation est aussi influencée par différentes émotions qui servent à adapter nos choix afin de, par exemple, éviter les paris excessivement risqués, prévenir les regrets futurs ou échapper aux rejets personnels ou aux conflits. En nous appuyant sur une théorie économique et sur les avancées des études des mécanismes neuronaux, nous analysons les essais récents pertinents chez les primates non humains et les observations cliniques faites chez des patients atteints neurologiquement et souffrant d'une perturbation de l'aptitude à la prise de décision.

Effects of MDMA Injections on the Behavior of Socially-Housed Long-Tailed Macaques (Macaca fascicularis).

3,4-methylenedioxy-N-methyl amphetamine (MDMA) is one of the few known molecules to increase human and rodent prosocial behaviors. However, this effect has never been assessed on the social behavior of non-human primates. In our study, we subcutaneously injected three different doses of MDMA (1.0, 1.5 or 2.0mg/kg) to a group of three, socially housed, young male long-tailed macaques. More than 200 hours of behavioral data were recorded, during 68 behavioral sessions, by an automatic color-based video device that tracked the 3D positions of each animal and of a toy. This data was then categorized into 5 exclusive behaviors (resting, locomotion, foraging, social contact and object play). In addition, received and given social grooming was manually scored. Results show several significant dose-dependent behavioral effects. At 1.5mg/kg only, MDMA induces a significant increase in social grooming behavior, thus confirming the prosocial effect of MDMA in macaques. Additionally, at 1.5 and 2.0 mg/kg MDMA injection substantially decreases foraging behavior, which is consistent with the known anorexigenic effect of this compound. Furthermore, at 2.0 mg/kg MDMA injection induces an increase in locomotor behavior, which is also in accordance with its known stimulant property. Interestingly, MDMA injected at 1.0mg/kg increases the rate of object play, which might be interpreted as a decrease of the inhibition to manipulate a unique object in presence of others, or, as an increase of the intrinsic motivation to manipulate this object. Together, our results support the effectiveness of MDMA to study the complex neurobiology of primates' social behaviors.

Independent Neuronal Representation of Facial and Vocal Identity in the Monkey Hippocampus and Inferotemporal Cortex.

Social interactions make up to a large extent the prime material of episodic memories. We therefore asked how social signals are coded by neurons in the hippocampus. Human hippocampus is home to neurons representing familiar individuals in an abstract and invariant manner ( Quian Quiroga et al. 2009). In contradistinction, activity of rat hippocampal cells is only weakly altered by the presence of other rats ( von Heimendahl et al. 2012; Zynyuk et al. 2012). We probed the activity of monkey hippocampal neurons to faces and voices of familiar and unfamiliar individuals (monkeys and humans). Thirty-one percent of neurons recorded without prescreening responded to faces or to voices. Yet responses to faces were more informative about individuals than responses to voices and neuronal responses to facial and vocal identities were not correlated, indicating that in our sample identity information was not conveyed in an invariant manner like in human neurons. Overall, responses displayed by monkey hippocampal neurons were similar to the ones of neurons recorded simultaneously in inferotemporal cortex, whose role in face perception is established. These results demonstrate that the monkey hippocampus participates in the read-out of social information contrary to the rat hippocampus, but possibly lack an explicit conceptual coding of as found in humans.

Rudimentary empathy in macaques' social decision-making.

Primates live in highly social environments, where prosocial behaviors promote social bonds and cohesion and contribute to group members' fitness. Despite a growing interest in the biological basis of nonhuman primates' social interactions, their underlying motivations remain a matter of debate. We report that macaque monkeys take into account the welfare of their peers when making behavioral choices bringing about pleasant or unpleasant outcomes to a monkey partner. Two macaques took turns in making decisions that could impact their own welfare or their partner's. Most monkeys were inclined to refrain from delivering a mildly aversive airpuff and to grant juice rewards to their partner. Choice consistency between these two types of outcome suggests that monkeys display coherent motivations in different social interactions. Furthermore, spontaneous affilitative group interactions in the home environment were mostly consistent with the measured social decisions, thus emphasizing the impact of preexisting social bonds on decision-making. Interestingly, unique behavioral markers predicted these decisions: benevolence was associated with enhanced mutual gaze and empathic eye blinking, whereas indifference or malevolence was associated with lower or suppressed such responses. Together our results suggest that prosocial decision-making is sustained by an intrinsic motivation for social affiliation and controlled through positive and negative vicarious reinforcements.