Learning about the world is critical to survival and success. In social animals, learning about others is a necessary component of navigating the social world, ultimately contributing to increasing evolutionary fitness. How humans and nonhuman animals represent the internal states and experiences of others has long been a subject of intense interest in the developmental psychology tradition, and, more recently, in studies of learning and decision making involving self and other. In this review, we explore how psychology conceptualizes the process of representing others, and how neuroscience has uncovered correlates of reinforcement learning signals to explore the neural mechanisms underlying social learning from the perspective of representing reward-related information about self and other. In particular, we discuss self-referenced and other-referenced types of reward prediction errors across multiple brain structures that effectively allow reinforcement learning algorithms to mediate social learning. Predictionbased computational principles in the brain may be strikingly conserved between self-referenced and other-referenced information.npj Science of Learning (2017) 2:8 ; doi:10.1038/s41539-017-0009-2 HISTORICAL PERSPECTIVES ON REPRESENTING OTHERLearning about the world and making adaptive decisions is a critical feature of cognition. This important link allows human and nonhuman animals to manipulate their environment and survive. Decision-making takes on more complex dynamics when an animal is not solitary, but lives in a community with other members of its own species. We know much about how human and nonhuman animals learn from their own actions and outcomes, and where such self-referenced information is represented in the brain. However, much less is known about the computations underlying how we learn about others. In this review, we examine the presence of other-referenced prediction errors in the brain that represent other's actions and reward outcomes.One of the first academic disciplines to attempt to understand how we develop a concept of others is developmental psychology, in which researchers often explore how babies come to understand the world.

Interpersonal interaction is the essence of human social behavior. However, conventional neuroimaging techniques have tended to focus on social cognition in single individuals rather than on dyads or groups. As a result, relatively little is understood about the neural events that underlie face-to-face interaction. We resolved some of the technical obstacles inherent in studying interaction using a novel imaging modality and aimed to identify neural mechanisms engaged both within and across brains in an ecologically valid instance of interpersonal competition. Functional near-infrared spectroscopy was utilized to simultaneously measure hemodynamic signals representing neural activity in pairs of subjects playing poker against each other (human–human condition) or against computer opponents (human–computer condition). Previous fMRI findings concerning single subjects confirm that neural areas recruited during social cognition paradigms are individually sensitive to human–human and human–computer conditions. However, it is not known whether face-to-face interactions between opponents can extend these findings. We hypothesize distributed effects due to live processing and specific variations in across-brain coherence not observable in single-subject paradigms. Angular gyrus (AG), a component of the temporal-parietal junction (TPJ) previously found to be sensitive to socially relevant cues, was selected as a seed to measure within-brain functional connectivity. Increased connectivity was confirmed between AG and bilateral dorsolateral prefrontal cortex (dlPFC) as well as a complex including the left subcentral area (SCA) and somatosensory cortex (SS) during interaction with a human opponent. These distributed findings were supported by contrast measures that indicated increased activity at the left dlPFC and frontopolar area that partially overlapped with the region showing increased functional connectivity with AG. Across-brain analyses of neural coherence between the players revealed synchrony between dlPFC and supramarginal gyrus (SMG) and SS in addition to synchrony between AG and the fusiform gyrus (FG) and SMG. These findings present the first evidence of a frontal-parietal neural complex including the TPJ, dlPFC, SCA, SS, and FG that is more active during human-to-human social cognition both within brains (functional connectivity) and across brains (across-brain coherence), supporting a model of functional integration of socially and strategically relevant information during live face-to-face competitive behaviors.

To provide new preclinical evidence toward improving the efficacy of oxytocin (OT) in treating social dysfunction, we tested the benefit of administering OT under simultaneously induced opioid antagonism during dyadic gaze interactions in monkeys. OT coadministered with a μ-opioid receptor antagonist, naloxone, invoked a supralinear enhancement of prolonged and selective social attention, producing a stronger effect than the summed effects of each administered separately. These effects were consistently observed when averaging over entire sessions, as well as specifically following events of particular social importance, including mutual eye contact and mutual reward receipt. Furthermore, attention to various facial regions was differentially modulated depending on social context. Using the Allen Institute's transcriptional atlas, we further established the colocalization of μ-opioid and κ-opioid receptor genes and OT genes at the OT-releasing sites in the human brain. These data across monkeys and humans support a regulatory relationship between the OT and opioid systems and suggest that administering OT under opioid antagonism may boost the therapeutic efficacy of OT for enhancing social cognition.T he efficacy of oxytocin (OT) in improving social abilities is under debate, largely due to frequently observed weak effect sizes and problems with replicability (1-3). Clinical trials of OT in autistic patients are ongoing, yet several studies have produced inconclusive results (4-8), demanding improvements to the efficacy and reliability of OT-based therapeutics. One strategy is to take advantage of existing physiological pathways in the brain that regulate OT activity to combinatorially enhance the oxytocinergic effects on social functions. In this regard, a promising candidate is the opioid system.In addition to the evolutionarily conserved OT system (9), the opioid system has been implicated in regulating social behavior. Excessive opioid activity in the brain has been discussed with respect to the development of early childhood autism (10). Abnormalities in central opioid levels have been observed in some individuals with autism, and clinical trials with predominantly μ-opioid blockers, such as naltrexone or naloxone (NAL), have yielded promising results in ameliorating both social and nonsocial deficits (11). Specifically, μ-opioid receptors have been studied in relation to reward, emotion, and behavior in the social domain (12) and are strongly expressed in reward-related regions of the primate brain (13). In rhesus macaques, carrying the G allele of the μ-opioid receptor gene OPRM1, compared with homozygous C alleles, is associated with stronger maternal attachment in infants (14) and more effective prevention of infant separation in mothers (15). Additionally, opioid agonists, such as morphine, decrease physical contact between social partners, whereas NAL administration increases solicitation for social contact, such as grooming and proximity (16)(17)(18)(19).The physiological relationship between the opi...

Few studies have addressed the neural computations underlying decisions made for others despite the importance of this ubiquitous behavior. Using participant-specific behavioral modeling with univariate and multivariate fMRI approaches, we investigated the neural correlates of decision-making for self and other in two independent tasks, including intertemporal and risky choice. Modeling subjective valuation indicated that participants distinguished between themselves and others with dissimilar preferences. Activity in the dorsomedial prefrontal cortex (dmPFC) and ventromedial prefrontal cortex (vmPFC) was consistently modulated by relative subjective value. Multi-voxel pattern analysis indicated that activity in the dmPFC uniquely encoded relative subjective value and generalized across self and other and across both tasks. Furthermore, agent cross-decoding accuracy between self and other in the dmPFC was related to self-reported social attitudes. These findings indicate that the dmPFC emerges as a medial prefrontal node that utilizes a task-invariant mechanism for computing relative subjective value for self and other.

The dynamic interaction of gaze between individuals is a hallmark of social cognition. However, very few studies have examined social gaze dynamics after mutual eye contact during real-time interactions. We used a highly quantifiable paradigm to assess social gaze dynamics between pairs of monkeys and modeled these dynamics using an exponential decay function to investigate sustained attention after mutual eye contact. When monkeys were interacting with real partners compared with static images and movies of the same monkeys, we found a significant increase in the proportion of fixations to the eyes and a smaller dispersion of fixations around the eyes, indicating enhanced focal attention to the eye region. Notably, dominance and familiarity between the interacting pairs induced separable components of gaze dynamics that were unique to live interactions. Gaze dynamics of dominant monkeys after mutual eye contact were associated with a greater number of fixations to the eyes, whereas those of familiar pairs were associated with a faster rate of decrease in this eye-directed attention. Our findings endorse the notion that certain key aspects of social cognition are only captured during interactive social contexts and dependent on the elapsed time relative to socially meaningful events.

Cholinergic modulation of prefrontal cortex is essential for attention. In essence, it focuses the mind on relevant, transient stimuli in support of goal-directed behavior. The excitation of prefrontal layer VI neurons through nicotinic acetylcholine receptors optimizes local and top-down control of attention. Layer VI of prefrontal cortex is the origin of a dense feedback projection to the thalamus and is one of only a handful of brain regions that express the α5 nicotinic receptor subunit, encoded by the gene chrna5. This accessory nicotinic receptor subunit alters the properties of high-affinity nicotinic receptors in layer VI pyramidal neurons in both development and adulthood. Studies investigating the consequences of genetic deletion of α5, as well as other disruptions to nicotinic receptors, find attention deficits together with altered cholinergic excitation of layer VI neurons and aberrant neuronal morphology. Nicotinic receptors in prefrontal layer VI neurons play an essential role in focusing attention under challenging circumstances. In this regard, they do not act in isolation, but rather in concert with cholinergic receptors in other parts of prefrontal circuitry. This review urges an intensification of focus on the cellular mechanisms and plasticity of prefrontal attention circuitry. Disruptions in attention are one of the greatest contributing factors to disease burden in psychiatric and neurological disorders, and enhancing attention may require different approaches in the normal and disordered prefrontal cortex.

Interest in the effects of oxytocin on social behavior has persisted even as an overarching theory describing these effects has remained largely elusive. Some of the earliest studies on the effects of oxytocin on social decision-making indicated that oxytocin might enhance prosocial actions directed toward others. This led to development of the prosocial hypothesis, which stipulates that oxytocin specifically enhances prosocial choices. However, further work indicated that oxytocin administration could elicit antisocial behaviors as well in certain social situations, highlighting the importance of context-dependent effects. At least two prominent hypotheses have been used to explain these seemingly contradictory findings. The social salience hypothesis indicates that the effects of oxytocin can be conceptualized as a general increase in the salience of social stimuli in the environment. Distinctly, the approach/withdrawal hypothesis stipulates that oxytocin enhances approach behaviors and decreases withdrawal behaviors. These phenomenologically motivated hypotheses regarding the effects of oxytocin on social behavior have created controversies in the field. In this review, we present a multistage framework of social decision-making designed to unify these disparate theories in a process common to all social decisions. We conceptualize this process as involving multiple distinct computational steps, including sensory input, sensory perception, valuation, decision formulation, and behavioral output. Iteratively, these steps generate social behaviors, and oxytocin could be acting on any of these steps to exert its effects. In support of this framework, we examine both behavioral and neural evidence across rodents, non-human primates, and humans, determining at what point in our multistage framework oxytocin could be eliciting its socially relevant effects. Finally, we postulate based on our framework that the prosocial, social salience, and approach/withdrawal hypotheses may not be mutually exclusive and could explain the influence of oxytocin on social behavior to different extents depending on context.

Developing neuronal growth cones respond to a number of post‐transcriptionally modified guidance cues to establish functional neural networks. The Semaphorin family has well‐established roles as both secreted and transmembrane guidance cues. Here, we describe the first evidence that a transmembrane Semaphorin, Semaphorin 5B (Sema5B), is proteolytically processed from its transmembrane form and can function as a soluble growth cone collapsing guidance cue. Over‐expression of A Disintegrin and Metalloprotease (ADAM)‐17, results in an enhanced release of the Sema5B ectodomain, while removal of a predicted ADAM‐17 cleavage site prevents its release. In contrast, knockdown of ADAM‐17 does not significantly reduce Sema5B release, indicating there are additional unknown compensating proteases. This modulation of the transmembrane Sema5B to a diffusible cue represents a sophisticated method to regulate neuronal guidance in vivo.