Closed-loop microstimulations of the orbitofrontal cortex during real-life gaze interaction enhance dynamic social attention.

Neurons from multiple prefrontal areas encode several key variables of social gaze interaction. To explore the causal roles of the primate prefrontal cortex in real-life gaze interaction, we applied weak closed-loop microstimulations that were precisely triggered by specific social gaze events. Microstimulations of the orbitofrontal cortex, but not the dorsomedial prefrontal cortex or the anterior cingulate cortex, enhanced momentary dynamic social attention in the spatial dimension by decreasing the distance of fixations relative to a partner's eyes and in the temporal dimension by reducing the inter-looking interval and the latency to reciprocate the other's directed gaze. By contrast, on a longer timescale, microstimulations of the dorsomedial prefrontal cortex modulated inter-individual gaze dynamics relative to one's own gaze positions. These findings demonstrate that multiple regions in the primate prefrontal cortex may serve as functionally accessible nodes in controlling different aspects of dynamic social attention and suggest their potential for a therapeutic brain interface.

An unbiased method to partition diverse neuronal responses into functional ensembles reveals interpretable population dynamics during innate social behavior.

In neuroscience, understanding how single-neuron firing contributes to distributed neural ensembles is crucial. Traditional methods of analysis have been limited to descriptions of whole population activity, or, when analyzing individual neurons, criteria for response categorization varied significantly across experiments. Current methods lack scalability for large datasets, fail to capture temporal changes and rely on parametric assumptions. There's a need for a robust, scalable, and non-parametric functional clustering approach to capture interpretable dynamics. To address this challenge, we developed a model-based, statistical framework for unsupervised clustering of multiple time series datasets that exhibit nonlinear dynamics into an a-priori-unknown number of parameterized ensembles called Functional Encoding Units (FEUs). FEU outperforms existing techniques in accuracy and benchmark scores. Here, we apply this FEU formalism to single-unit recordings collected during social behaviors in rodents and primates and demonstrate its hypothesis-generating and testing capacities. This novel pipeline serves as an analytic bridge, translating neural ensemble codes across model systems.

Autonomic and hedonic response to affective touch in autism spectrum disorder.

Interpersonal touch plays a crucial role in shaping relationships and encouraging social connections. Failure in processing tactile input or abnormal tactile sensitivity may hamper social behaviors and have severe consequences in individuals' relational lives. Autism Spectrum Disorder (ASD) is characterized by both sensory disruptions and social impairments, making affective touch an ideal meeting point for understanding these features in ASD individuals. By integrating behavioral and physiological measures, we investigated the effects of affective touch on adult individuals with ASD from both an implicit and explicit perspective. Specifically, at an implicit level, we investigated whether and how receiving an affective touch influenced participants' skin conductance tonic and phasic components. At the explicit level, we delved into the affective and unpleasant features of affective touch. Overall, we observed lower skin conductance level in ASD compared to TD subjects. Interestingly, the typically developing (TD) group showed an increased autonomic response for affective touch compared to a control touch, while ASD subjects' autonomic response did not differ between the two conditions. Furthermore, ASD participants provided higher ratings for both the affective and unpleasant components of the touch, compared to TD subjects. Our results reveal a noteworthy discrepancy in ASD population between the subjective experience, characterized by amplified hedonic but also unpleasant responses, and the physiological response, marked by a lack of autonomic activation related to affective touch. This insightful dissociation seems crucial for a deeper understanding of the distinctive challenges characterizing people with ASD and may have implications for diagnosis and therapeutic approaches.

Hedonic and autonomic responses in promoting affective touch.

Interpersonal touch is intrinsically reciprocal since it entails a person promoting and another receiving the touch. While several studies have investigated the beneficial effects of receiving affective touch, the affective experience of caressing another individual remains largely unknown. Here, we investigated the hedonic and autonomic responses (skin conductance and heart rate) in the person promoting affective touch. We also examined whether interpersonal relationship, gender, and eye contact modulate these responses. As expected, caressing the partner was perceived as more pleasant than caressing a stranger, especially if the affective touch occurred together with mutual eye contact. Promoting affective touch to the partner also resulted in a decrease of both autonomic responses and anxiety levels, suggesting the occurrence of a calming effect. Additionally, these effects were more pronounced in females compared to males, indicating that hedonic and autonomic aspects of affective touch are modulated by both social relationship and gender. These findings show for the first time that caressing a beloved one is not only pleasant but also reduces autonomic responses and anxiety in the person promoting the touch. This might suggest that affective touch has an instrumental role for romantic partners in promoting and reinforcing their affective bonding.

Dissociation of vicarious and experienced rewards by coupling frequency within the same neural pathway.

Vicarious reward, essential to social learning and decision making, is theorized to engage select brain regions similarly to experienced reward to generate a shared experience. However, it is just as important for neural systems to also differentiate vicarious from experienced rewards for social interaction. Here, we investigated the neuronal interaction between the primate anterior cingulate cortex gyrus (ACCg) and the basolateral amygdala (BLA) when social choices made by monkeys led to either vicarious or experienced reward. Coherence between ACCg spikes and BLA local field potential (LFP) selectively increased in gamma frequencies for vicarious reward, whereas it selectively increased in alpha/beta frequencies for experienced reward. These respectively enhanced couplings for vicarious and experienced rewards were uniquely observed following voluntary choices. Moreover, reward outcomes had consistently strong directional influences from ACCg to BLA. Our findings support a mechanism of vicarious reward where social agency is tagged by interareal coordination frequency within the same shared pathway.

Pain perception and physiological responses are modulated by active support from a romantic partner.

As social animals, humans are strongly affected by social bonds and interpersonal interactions. Proximity and social support from significant others may buffer the negative outcomes of a painful experience. Several studies have investigated the role of romantic partners' support in pain modulation, mostly focusing on tactile support and showing its effectiveness in reducing pain perception. Nevertheless, no study so far has investigated the role of supportive speaking on pain modulation, nor has compared the effects of a tactile and vocal support within the same couples. The present study directly compared for the first time the efficacy of mere presence (Passive Support) and different forms of active (Touch, Voice, Touch + Voice) support from a romantic partner during a painful experience in a naturalistic setting. We assessed pain modulation in 37 romantic couples via both subjective (self-reported ratings) and physiological (skin conductance) measurements. We found that all three types of active support were equally more effective than passive support in reducing the painful experience at both subjective and physiological levels; interestingly, our results suggest that supportive speaking can reduce pain perception with respect to passive support to a similar extent as tactile support does. Overall, this study highlights the relevance of an active support in reducing pain perception, with active types of support being more effective than passive support, regardless of its specific modality.

Beyond alpha-band: The neural correlate of creative thinking.

The compound nature of creativity entails the interplay of multiple cognitive processes, making it difficult to attribute creativity to a single neural signature. Divergent thinking paradigms, widely adopted to investigate creative production, have highlighted the key role of specific mental operations subserving creativity, such as inhibition of external stimuli, loose semantic associations, and mental imagery. Neurophysiological studies have typically shown a high alpha rhythm synchronization when individuals are engaged in creative ideation. Also, oculomotor activity and pupil diameter have been proposed as useful indicators of mental operations involved in such a thinking process. The goal of this study was to investigate whether beyond alpha-band activity other higher frequency bands, such as beta and gamma, may subserve divergent and convergent thinking and whether those could be associated with a different gaze bias and pupil response during ideas generation. Implementing a within-subjects design we collected behavioral measures, neural activity, gaze patterns, and pupil dilation while participants performed a revised version of the Alternative Uses Task, in which divergent thinking is contrasted to convergent thinking. As expected, participants took longer to generate creative ideas as compared to common ones. Interestingly, during divergent thinking participants displayed alpha synchronization along with beta and gamma desynchronization, more pronounced leftward gaze shift, and greater pupil dilation. During convergent thinking, an opposite pattern was observed: desynchronization in alpha and an increase in beta and gamma rhythm, along with a reduction of leftward gaze shift and greater pupil constriction. The present study uncovered specific neural dynamics and physiological patterns during idea generation, providing novel insight into the complex physiological signature of creative production.

Closed-loop microstimulations of the orbitofrontal cortex during real-life gaze interaction enhance dynamic social attention.

The prefrontal cortex is extensively involved in social exchange. During dyadic gaze interaction, multiple prefrontal areas exhibit neuronal encoding of social gaze events and context-specific mutual eye contact, supported by a widespread neural mechanism of social gaze monitoring. To explore causal manipulation of real-life gaze interaction, we applied weak closed-loop microstimulations that were precisely triggered by specific social gaze events to three prefrontal areas in monkeys. Microstimulations of orbitofrontal cortex (OFC), but not dorsomedial prefrontal or anterior cingulate cortex, enhanced momentary dynamic social attention in the spatial dimension by decreasing distance of one's gaze fixations relative to partner monkey's eyes. In the temporal dimension, microstimulations of OFC reduced the inter-looking interval for attending to another agent and the latency to reciprocate other's directed gaze. These findings demonstrate that primate OFC serves as a functionally accessible node in controlling dynamic social attention and suggest its potential for a therapeutic brain interface.

Widespread implementations of interactive social gaze neurons in the primate prefrontal-amygdala networks.

Social gaze interaction powerfully shapes interpersonal communication. However, compared with social perception, very little is known about the neuronal underpinnings of real-life social gaze interaction. Here, we studied a large number of neurons spanning four regions in primate prefrontal-amygdala networks and demonstrate robust single-cell foundations of interactive social gaze in the orbitofrontal, dorsomedial prefrontal, and anterior cingulate cortices, in addition to the amygdala. Many neurons in these areas exhibited high temporal heterogeneity for social discriminability, with a selectivity bias for looking at a conspecific compared with an object. Notably, a large proportion of neurons in each brain region parametrically tracked the gaze of self or other, providing substrates for social gaze monitoring. Furthermore, several neurons displayed selective encoding of mutual eye contact in an agent-specific manner. These findings provide evidence of widespread implementations of interactive social gaze neurons in the primate prefrontal-amygdala networks during social gaze interaction.

Self-other distinction modulates the social softness illusion.

The social softness illusion (i.e., the tendency to perceive another person's skin as softer than our own) is thought to promote the sharing of social-emotional experiences because of the rewarding properties of receiving and giving social affective touch. Here we investigated whether the ability to distinguish someone else's body from our own modulates the social softness illusion. In particular, we tested whether the spatial perspective taken by the participants and seeing or not the touched arms could alter this illusion. Pairs of female participants were assigned the roles of either the giver (i.e., delivering the touches) or the receiver (i.e., being touched). We manipulated the location of the touch (palm or forearm), the spatial perspective of the receiver's body with respect to the giver's body (egocentric or allocentric perspective), and the vision of the touched body part (the giver could either see both her own and the receiver's body part, or she was blindfolded). Consistently with previous findings, the skin of another person was perceived as softer than the own one. Additionally, the illusion was present for both the forearm and the palm, and it was stronger in allocentric compared to the egocentric perspective (i.e., when the self-other distinction was clearer). These findings show that the mechanisms underpinning the ability to represent another person's body as distinct from our own modulates the social softness illusion, and thus support the role of the social softness illusion in fostering social relationships.

Increasing Central Serotonin with 5-hydroxytryptophan Disrupts the Inhibition of Social Gaze in Nonhuman Primates.

To competently navigate the world, individuals must flexibly balance distinct aspects of social gaze, orienting toward others and inhibiting orienting responses, depending on the context. These behaviors are often disrupted amongst patient populations treated with serotonergic drugs. However, those in the field lack a clear understanding of how the serotonergic system mediates social orienting and inhibiting behaviors. Here, we tested how increasing central concentrations of serotonin with the direct precursor 5-hydroxytryptophan (5-HTP) would modulate the ability of rhesus macaques (both sexes) to use eye movements to flexibly orient to, or inhibit orienting to, faces. Systemic administrations of 5-HTP effectively increased central serotonin levels and impaired flexible orientation and inhibition. Critically, 5-HTP selectively impaired the ability of monkeys to inhibit orienting to face images, whereas it similarly impaired orienting to face and control images. 5-HTP also caused monkeys to perseverate on their gaze responses, making them worse at flexibly switching between orienting and inhibiting behaviors. Furthermore, the effects of 5-HTP on performance correlated with a constriction of the pupil, an increased time to initiate trials, and an increased reaction time, suggesting that the disruptive effects of 5-HTP on social gaze behaviors are likely driven by a downregulation of arousal and motivational states. Together, these findings provide causal evidence for a modulatory relationship between 5-HTP and social gaze behaviors in nonhuman primates and offer translational insights for the role of the serotonergic system in social gaze.SIGNIFICANCE STATEMENT Behavioral changes arising from pharmacological agents that target serotonergic functions are complex and difficult to predict. Here, we examined the causal impacts of administering the direct precursor of serotonin, 5-HTP, on orienting and inhibiting social gaze in nonhuman primates. 5-HTP increased central concentrations of serotonin and selectively impaired the ability of monkeys to inhibit orienting to faces while similarly impairing the ability of monkeys to orient to face and control images. These behavioral gaze impairments were systematically associated with a downregulation of arousal and motivational states, indexed by pupil constriction, increased time to initiate trials, and increased reaction time. These findings provide a causal link between 5-HTP and social gaze behaviors in nonhuman primates and provide translational insights about serotonergic interventions.

Changing your body changes your eating attitudes: embodiment of a slim virtual avatar induces avoidance of high-calorie food.

The virtual-reality full-body illusion paradigm has been suggested to not only trigger the illusory ownership of the avatar's body but also the attitudinal and behavioral components stereotypically associated to that kind of virtual body. In the present study, we investigated whether this was true for stereotypes related to body size: body satisfaction and eating control behavior. Healthy participants underwent the full-body illusion paradigm with an avatar having either a larger or a slimmer body than their own, and were assessed for implicit attitudes towards body image and food calorie content at baseline and after each full-body illusion session. Results showed that the illusion emerged regardless of the avatar's body size, whereas the perceived dimension of the own body size changed according to the avatar's body size (i.e., participants felt to be slimmer after embodying their slim avatar and larger after embodying their large avatar). Crucially, we found that implicit attitudes towards food, but not those towards one's own body, were modulated by the size of the virtual body. Compared to baseline, ownership of a slimmer avatar increased the avoidance of high-calorie food, whereas ownership of a larger avatar did not induce changes. Our findings suggest that the illusory feeling of being slimmer drives also the food-related stereotypes associated with that body size, increasing the regulation of eating behaviors.

Autonomic arousal tracks outcome salience not valence in monkeys making social decisions.

The evolutionary and neural underpinnings of human prosociality are still being identified. A growing body of evidence suggests that some species find the sight of another individual receiving a reward reinforcing, called vicarious reinforcement, and that this capacity is supported by a network of brain areas including the anterior cingulate cortex (ACC) and the amygdala. At the same time, analyses of autonomic arousal have been increasingly used to contextualize and guide neural research, especially for studies of reward processing. Here, we characterized the autonomic pupil response of eight monkeys across two laboratories in two different versions of a vicarious reinforcement paradigm. Monkeys were cued as to whether an upcoming reward would be delivered to them, another monkey, or nobody and could accept or decline the offer. As expected, all monkeys in both laboratories showed a marked preference for juice to the self, together with a reliable prosocial preference for juice to a social partner compared to juice to nobody. However, contrary to our expectations, we found that pupils were widest in anticipation of juice to the self, moderately sized in anticipation of juice to nobody, and narrowest in anticipation of juice to a social partner. This effect was seen across both laboratories and regardless of specific task parameters. The seemingly paradoxical pupil effect can be explained by a model in which pupil size tracks outcome salience, prosocial tendencies track outcome valence, and the relation between salience and valence is U-shaped. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Levels of naturalism in social neuroscience research.

In order to understand ecologically meaningful social behaviors and their neural substrates in humans and other animals, researchers have been using a variety of social stimuli in the laboratory with a goal of extracting specific processes in real-life scenarios. However, certain stimuli may not be sufficiently effective at evoking typical social behaviors and neural responses. Here, we review empirical research employing different types of social stimuli by classifying them into five levels of naturalism. We describe the advantages and limitations while providing selected example studies for each level. We emphasize the important trade-off between experimental control and ecological validity across the five levels of naturalism. Taking advantage of newly emerging tools, such as real-time videos, virtual avatars, and wireless neural sampling techniques, researchers are now more than ever able to adopt social stimuli at a higher level of naturalism to better capture the dynamics and contingency of real-life social interaction.

Right and left inferior frontal opercula are involved in discriminating angry and sad facial expressions.

BACKGROUND: Neuroimaging studies suggest that the inferior frontal operculum (IFO) is part of a neuronal network involved in facial expression processing, but the causal role of this region in emotional face discrimination remains elusive. OBJECTIVE: We used cathodal (inhibitory) tDCS to test whether right (r-IFO) and left (l-IFO) IFO play a role in discriminating basic facial emotions in healthy volunteers. Specifically, we tested if the two sites are selectively involved in the processing of facial expressions conveying high or low arousal emotions. Based on the Arousal Hypothesis we expected to find a modulation of high and low arousal emotions by cathodal tDCS of the r-IFO and the l-IFO, respectively. METHODS: First, we validated an Emotional Faces Discrimination Task (EFDT). Then, we targeted the r-IFO and the l-IFO with cathodal tDCS (i.e. the cathode was placed over the right or left IFO, while the anode was placed over the contralateral supraorbital area) during facial emotions discrimination on the EFDT. Non-active (i.e. sham) tDCS was a control condition. RESULTS: Overall, participants manifested the "happy face advantage". Interestingly, tDCS to r-IFO enhanced discrimination of faces expressing anger (a high arousal emotion), whereas, tDCS to l-IFO decreased discrimination of faces expressing sadness (a low arousal emotion). CONCLUSIONS: Our findings revealed a differential causal role of r-IFO and l-IFO in the discrimination of specific high and low arousal emotions. Crucially, these results suggest that cathodal tDCS might reduce the neural noise triggered by facial emotions, improving discrimination of high arousal emotions but disrupting discrimination of low arousal emotions. These findings offer new insights for treating clinical population with deficits in processing facial expressions.

Disentangling perceptual awareness from nonconscious processing in rhesus monkeys (Macaca mulatta).

Scholars have long debated whether animals, which display impressive intelligent behaviors, are consciously aware or not. Yet, because many complex human behaviors and high-level functions can be performed without conscious awareness, it was long considered impossible to untangle whether animals are aware or just conditionally or nonconsciously behaving. Here, we developed an empirical approach to address this question. We harnessed a well-established cross-over double dissociation between nonconscious and conscious processing, in which people perform in completely opposite ways when they are aware of stimuli versus when they are not. To date, no one has explored if similar performance dissociations exist in a nonhuman species. In a series of seven experiments, we first established these signatures in humans using both known and newly developed nonverbal double-dissociation tasks and then identified similar signatures in rhesus monkeys (Macaca mulatta). These results provide robust evidence for two distinct modes of processing in nonhuman primates. This empirical approach makes it feasible to disentangle conscious visual awareness from nonconscious processing in nonhuman species; hence, it can be used to strip away ambiguity when exploring the processes governing intelligent behavior across the animal kingdom. Taken together, these results strongly support the existence of both nonconscious processing as well as functional human-like visual awareness in nonhuman animals.

Prefrontal-amygdala circuits in social decision-making.

An increasing amount of research effort is being directed toward investigating the neural bases of social cognition from a systems neuroscience perspective. Evidence from multiple animal species is beginning to provide a mechanistic understanding of the substrates of social behaviors at multiple levels of neurobiology, ranging from those underlying high-level social constructs in humans and their more rudimentary underpinnings in monkeys to circuit-level and cell-type-specific instantiations of social behaviors in rodents. Here we review literature examining the neural mechanisms of social decision-making in humans, non-human primates and rodents, focusing on the amygdala and the medial and orbital prefrontal cortical regions and their functional interactions. We also discuss how the neuropeptide oxytocin impacts these circuits and their downstream effects on social behaviors. Overall, we conclude that regulated interactions of neuronal activity in the prefrontal-amygdala pathways critically contribute to social decision-making in the brains of primates and rodents.

Specialized medial prefrontal-amygdala coordination in other-regarding decision preference.

Social behaviors recruit multiple cognitive operations that require interactions between cortical and subcortical brain regions. Interareal synchrony may facilitate such interactions between cortical and subcortical neural populations. However, it remains unknown how neurons from different nodes in the social brain network interact during social decision-making. Here we investigated oscillatory neuronal interactions between the basolateral amygdala and the rostral anterior cingulate gyrus of the medial prefrontal cortex while monkeys expressed context-dependent positive or negative other-regarding preference (ORP), whereby decisions affected the reward received by another monkey. Synchronization between the two nodes was enhanced for a positive ORP but suppressed for a negative ORP. These interactions occurred in beta and gamma frequency bands depending on the area contributing the spikes, exhibited a specific directionality of information flow associated with a positive ORP and could be used to decode social decisions. These findings suggest that specialized coordination in the medial prefrontal-amygdala network underlies social-decision preferences.

Combinatorial Oxytocin Neuropharmacology in Social Cognition.

The efficacy and reliability of using intranasal oxytocin (OT) to clinically enhance social functions remains undependable. We discuss the potential benefit of concurrent administration of OT and naloxone (NAL) to robustly modulate social behavior. We further suggest that combinatorial neuropharmacology approaches should exploit the interactions between OT and serotonin to regulate social functions.

Cross-species convergence in pupillary response: understanding human anxiety via non-human primate amygdala lesion.

Few studies have used matched affective paradigms to compare humans and non-human primates. In monkeys with amygdala lesions and youth with anxiety disorders, we examined cross-species pupillary responses during a saccade-based, affective attentional capture task. Given evidence of enhanced amygdala function in anxiety, we hypothesized that opposite patterns would emerge in lesioned monkeys and anxious participants. A total of 53 unmedicated youths (27 anxious, 26 healthy) and 8 adult male rhesus monkeys (Macaca mulatta) completed matched behavioral paradigms. Four monkeys received bilateral excitotoxic amygdala lesions and four served as unoperated controls. Compared to healthy youth, anxious youth exhibited increased pupillary constriction in response to emotional and non-emotional distractors (F(1,48) = 6.28, P = 0.02, η2p = 0.12). Pupillary response was associated significantly with anxiety symptoms severity (F(1,48) = 5.59, P = 0.02, η2p = 0.10). As hypothesized, lesioned monkeys exhibited the opposite pattern i.e. decreased pupillary constriction in response to distractors, compared to unoperated control monkeys (F(1,32) = 24.22, P < 0.001, η2 = 0.33). Amygdala lesioned monkeys and youth with anxiety disorders show opposite patterns of pupil constriction in the context of an affective distractor task. Such findings suggest the presence of altered amygdala circuitry functioning in anxiety. Future lesion and human neuroimaging work might examine the way in which specific amygdala sub-nuclei and downstream circuits mediate these effects.