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.

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.

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.

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.

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.

Differential dynamics of spatial attention, position, and color coding within the parietofrontal network.

Despite an ever growing knowledge on how parietal and prefrontal neurons encode low-level spatial and color information or higher-level information, such as spatial attention, an understanding of how these cortical regions process neuronal information at the population level is still missing. A simple assumption would be that the function and temporal response profiles of these neuronal populations match that of its constituting individual cells. However, several recent studies suggest that this is not necessarily the case and that the single-cell approach overlooks dynamic changes in how information is distributed over the neuronal population. Here, we use a time-resolved population pattern analysis to explore how spatial position, spatial attention and color information are differentially encoded and maintained in the macaque monkey prefrontal (frontal eye fields) and parietal cortex (lateral intraparietal area). Overall, our work brings about three novel observations. First, we show that parietal and prefrontal populations operate in two distinct population regimens for the encoding of sensory and cognitive information: a stationary mode and a dynamic mode. Second, we show that the temporal dynamics of a heterogeneous neuronal population brings about complementary information to that of its functional subpopulations. Thus, both need to be investigated in parallel. Last, we show that identifying the neuronal configuration in which a neuronal population encodes given information can serve to reveal this same information in a different context. All together, this work challenges common views on neural coding in the parietofrontal network.

Modulation of value representation by social context in the primate orbitofrontal cortex.

Primates depend for their survival on their ability to understand their social environment, and their behavior is often shaped by social circumstances. We report that the orbitofrontal cortex, a brain region involved in motivation and reward, is tuned to social information. Macaque monkeys worked to collect rewards for themselves and two monkey partners. Behaviorally, monkeys discriminated between cues signaling large and small [corrected] rewards, and between cues signaling rewards to self only and reward to both self and another monkey, with a preference for the former over the latter in both instances. Single neurons recorded during this task encoded the meaning of visual cues that predicted the magnitude of future rewards, as well as the motivational value of rewards obtained in a social context. Furthermore, neuronal activity was found to track momentary social preferences and partner's identity and social rank. The orbitofrontal cortex thus contains key neuronal mechanisms for the evaluation of social information.

A functional hierarchy within the parietofrontal network in stimulus selection and attention control.

Although we are confronted with an ever-changing environment, we do not have the capacity to analyze all incoming sensory information. Perception is selective and is guided both by salient events occurring in our visual field and by cognitive premises about what needs our attention. Although the lateral intraparietal area (LIP) and frontal eye field (FEF) are known to represent the position of visual attention, their respective contributions to its control are still unclear. Here, we report LIP and FEF neuronal activities recorded while monkeys performed a voluntary attention-orientation target-detection task. We show that both encode behaviorally significant events, but that the FEF plays a specific role in mapping abstract cue instructions onto a spatial priority map to voluntarily guide attention. On the basis of a latency analysis, we show that the coding of stimulus identity and position precedes the emergence of an explicit attentional signal within the FEF. We also describe dynamic temporal hierarchies between LIP and FEF: stimuli carrying the highest intrinsic saliency are signaled by LIP before FEF, whereas stimuli carrying the highest extrinsic saliency are signaled in FEF before LIP. This suggests that whereas the parietofrontal attentional network most probably processes visual information in a recurrent way, exogenous processing predominates in the parietal cortex and the endogenous control of attention takes place in the FEF.

Spontaneous voice-face identity matching by rhesus monkeys for familiar conspecifics and humans.

Recognition of a particular individual occurs when we reactivate links between current perceptual inputs and the previously formed representation of that person. This recognition can be achieved by identifying, separately or simultaneously, distinct elements such as the face, silhouette, or voice as belonging to one individual. In humans, those different cues are linked into one complex conceptual representation of individual identity. Here we tested whether rhesus macaques (Macaca mulatta) also have a cognitive representation of identity by evaluating whether they exhibit cross-modal individual recognition. Further, we assessed individual recognition of familiar conspecifics and familiar humans. In a free preferential looking time paradigm, we found that, for both species, monkeys spontaneously matched the faces of known individuals to their voices. This finding demonstrates that rhesus macaques possess a cross-modal cognitive representation of individuals that extends from conspecifics to humans, revealing the adaptive potential of identity recognition for individuals of socioecological relevance.

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.

Promoting social behavior with oxytocin in high-functioning autism spectrum disorders.

Social adaptation requires specific cognitive and emotional competences. Individuals with high-functioning autism or with Asperger syndrome cannot understand or engage in social situations despite preserved intellectual abilities. Recently, it has been suggested that oxytocin, a hormone known to promote mother-infant bonds, may be implicated in the social deficit of autism. We investigated the behavioral effects of oxytocin in 13 subjects with autism. In a simulated ball game where participants interacted with fictitious partners, we found that after oxytocin inhalation, patients exhibited stronger interactions with the most socially cooperative partner and reported enhanced feelings of trust and preference. Also, during free viewing of pictures of faces, oxytocin selectively increased patients' gazing time on the socially informative region of the face, namely the eyes. Thus, under oxytocin, patients respond more strongly to others and exhibit more appropriate social behavior and affect, suggesting a therapeutic potential of oxytocin through its action on a core dimension of autism.

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.

The relationship between spatial attention and saccades in the frontoparietal network of the monkey.

Spatial attention bears a remarkable resemblance to saccadic eye movements from both a behavioural and a neurophysiological point of view. In this review, we examine the contributions of two cortical areas, namely the lateral intraparietal area (LIP) and frontal eye field (FEF), to saccades and attention and discuss the possible interactions between these two areas. Based on the results of electrophysiological studies and on inactivation studies performed in the macaque monkey, we propose that LIP is mainly involved in salience representation and an attentional selection mechanism that underlies saccade guidance, at least when two objects or locations are in competition in the visual environment. In contrast, we suggest that FEF is involved in coding and triggering saccadic eye movements, as well as in coding the location of attention or the attentional shifts. However, these two functions subserved by the FEF are dissociable at a neuronal level. Saccade planning and attentional selection are intimately coupled from a behavioural point of view but correspond to distinct functional operations.

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.

Optimal sensorimotor control in eye movement sequences.

Fast and accurate motor behavior requires combining noisy and delayed sensory information with knowledge of self-generated body motion; much evidence indicates that humans do this in a near-optimal manner during arm movements. However, it is unclear whether this principle applies to eye movements. We measured the relative contributions of visual sensory feedback and the motor efference copy (and/or proprioceptive feedback) when humans perform two saccades in rapid succession, the first saccade to a visual target and the second to a memorized target. Unbeknownst to the subject, we introduced an artificial motor error by randomly "jumping" the visual target during the first saccade. The correction of the memory-guided saccade allowed us to measure the relative contributions of visual feedback and efferent copy (and/or proprioceptive feedback) to motor-plan updating. In a control experiment, we extinguished the target during the saccade rather than changing its location to measure the relative contribution of motor noise and target localization error to saccade variability without any visual feedback. The motor noise contribution increased with saccade amplitude, but remained <30% of the total variability. Subjects adjusted the gain of their visual feedback for different saccade amplitudes as a function of its reliability. Even during trials where subjects performed a corrective saccade to compensate for the target-jump, the correction by the visual feedback, while stronger, remained far below 100%. In all conditions, an optimal controller predicted the visual feedback gain well, suggesting that humans combine optimally their efferent copy and sensory feedback when performing eye movements.

Salience representation in the parietal and frontal cortex.

Some objects in the visual field are more likely to attract attention because they are either intrinsically eye catching or relevant in the context of a particular task. These two factors, known as stimulus-driven and goal-directed factors, respectively, are thought to be integrated into a unique salience map, possibly located in the frontal or the parietal cortex. However, the distinct contribution of these two regions to salience representation is difficult to establish experimentally and remains debated. In an attempt to address this issue, we designed several dual tasks composed of a letter reporting task and a visual search task, allowing us to quantify the salience of each visual item by measuring its probability to be selected by attention. In Experiment 1, the salience of the visual search items depended on a combination of conspicuity and relevance factors, whereas in Experiment 2, stimulus-driven and goal-directed factors were tested separately. Then, we used transcranial magnetic stimulation to interfere transiently with the function of the right angular gyrus (ANG) or right FEFs in healthy subjects performing these dual tasks. We found that interfering with the ANG and the FEF function specifically altered the influence of salience on the letter report rate without affecting the overall letter reporting rate, suggesting that these areas are involved in salience representation. In particular, the present study suggests that ANG is involved in goal-directed salience representation, whereas FEF would rather house a global salience map integrating both goal-directed and stimulus-driven factors.

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.