Jamil Zaki

Social effects of oxytocin in humans: context and person matter

Building on animal research, the past decade has witnessed a surge of interest in the effects of oxytocin on social cognition and prosocial behavior in humans. This work has generated considerable excitement about identifying the neurochemical underpinnings of sociality in humans, and discovering compounds to treat social functioning deficits. Inspection of the literature, however, reveals that the effects of oxytocin in the social domain are often weak and/or inconsistent. We propose that this literature can be informed by an interactionist approach in which the effects of oxytocin are constrained by features of situations and/or individuals. We show how this approach can improve understanding of extant research, suggest novel mechanisms through which oxytocin might operate, and refine predictions about oxytocin pharmacotherapy.

Oxytocin Selectively Improves Empathic Accuracy

Oxytocin is known to regulate prosocial behavior and social cognition in animals (Ross & Young, 2009), and recent studies suggest that oxytocin may have similar functions in humans. For example, oxytocin increases trust (Kosfeld, Heinrichs, Zak, Fischbacher, & Fehr, 2005) and accuracy in mental-state attribution (Domes, Heinrichs, Michel, Berger, & Herpertz, 2007; Guastella et al., 2009). These findings have generated excitement about oxytocin’s potential to ameliorate social deficits in such disorders as social phobia and autism (Bartz & Hollander, 2006; Guastella et al., 2009; Kosfeld et al., 2005). This excitement has not been confined to the scientific community: Dubbed the “hormone of love,” oxytocin is a common topic in the popular press. Is oxytocin truly a universal social panacea? Although some studies have shown that oxytocin improves social cognition and empathy (Domes et al., 2007; Guastella et al., 2009), others have not (Singer et al., 2008). Even studies demonstrating positive effects have ambiguities: Domes et al. (2007) found that oxytocin improved performance for difficult—but not easy—test items. These observations imply that rather than working universally, oxytocin may selectively facilitate social cognition given certain constraints. For example, by altering specific motivational or cognitive states, oxytocin might increase the salience of social cues, which in turn could improve social-cognitive performance for some individuals, but not others. The effects of oxytocin, then, should be most pronounced in individuals who—at baseline—are less socially proficient; this would be consistent with broader interactionist views emphasizing that individual differences in competencies interact with situational variables to determine behavior (Mischel & Shoda, 1995). To test whether normal variance in social proficiency moderates the effects of oxytocin on social-cognitive performance, we used a randomized, double-blind, placebo-controlled, crossover challenge in which participants received either intranasal oxytocin or a placebo and performed an empathicaccuracy task that naturalistically measures social-cognitive abilities (Zaki, Bolger, & Ochsner, 2008). We measured variance in baseline social competencies with the Autism Spectrum Quotient (AQ; Baron-Cohen, Wheelwright, Skinner, Martin, & Clubley, 2001), a self-report instrument that predicts social-cognitive performance (Baron-Cohen, Wheelwright, Hill, Raste, & Plumb, 2001). We hypothesized that drug condition and AQ score would interact to predict performance on the empathic-accuracy task, with oxytocin having the most pronounced effects for less socially proficient individuals (i.e., those with higher AQ scores).

The neural bases of empathic accuracy

Theories of empathy suggest that an accurate understanding of anothers emotions should depend on affective, motor, and/or higher cognitive brain regions, but until recently no experimental method has been available to directly test these possibilities. Here, we present a functional imaging paradigm that allowed us to address this issue. We found that empathically accurate, as compared with inaccurate, judgments depended on (i) structures within the human mirror neuron system thought to be involved in shared sensorimotor representations, and (ii) regions implicated in mental state attribution, the superior temporal sulcus and medial prefrontal cortex. These data demostrate that activity in these 2 sets of brain regions tracks with the accuracy of attributions made about anothers internal emotional state. Taken together, these results provide both an experimental approach and theoretical insights for studying empathy and its dysfunction.

Effects of oxytocin on recollections of maternal care and closeness

Although the infant–caregiver attachment bond is critical to survival, little is known about the biological mechanisms supporting attachment representations in humans. Oxytocin plays a key role in attachment bond formation and maintenance in animals and thus could be expected to affect attachment representations in humans. To investigate this possibility, we administered 24 IU intranasal oxytocin to healthy male adults in a double-blind, placebo-controlled, crossover designed study and then assessed memories of childhood maternal care and closeness—two features of the attachment bond. We found that the effects of oxytocin were moderated by the attachment representations people possess, with less anxiously attached individuals remembering their mother as more caring and close after oxytocin (vs. placebo) but more anxiously attached individuals remembering their mother as less caring and close after oxytocin (vs. placebo). These data contrast with the popular notion that oxytocin has broad positive effects on social perception and are more consistent with the animal literature, which emphasizes oxytocins role in encoding social memories and linking those memories to the reward value of the social stimulus.

Social Influence Modulates the Neural Computation of Value

Social influence—individuals’ tendency to conform to the beliefs and attitudes of others—has interested psychologists for decades. However, it has traditionally been difficult to distinguish true modification of attitudes from mere public compliance with social norms; this study addressed this challenge using functional neuroimaging. Participants rated the attractiveness of faces and subsequently learned how their peers ostensibly rated each face. Participants were then scanned using functional MRI while they rated each face a second time. The second ratings were influenced by social norms: Participants changed their ratings to conform to those of their peers. This social influence was accompanied by modulated engagement of two brain regions associated with coding subjective value—the nucleus accumbens and orbitofrontal cortex—a finding suggesting that exposure to social norms affected participants’ neural representations of value assigned to stimuli. These findings document the utility of neuroimaging to demonstrate the private acceptance of social norms.

Different circuits for different pain: Patterns of functional connectivity reveal distinct networks for processing pain in self and others

Abstract The ability to empathize with the suffering of others is critical for maintaining relationships and engaging in prosocial behavior. Recently, a series of studies have demonstrated that while watching other people experience pain (other pain), participants engage the anterior insula (AI) and anterior cingulate cortex (ACC), brain regions involved in the direct experience of pain (self pain). Here we test the hypothesis that common activity in ACC and AI may reflect the operation of distinct but overlapping networks of regions that support perception of self or other pain. To address this possibility, we scanned participants using fMRI while they received noxious thermal stimulation (self pain) or watched short videos of other people sustaining painful injuries (other pain). We isolated overlapping regions for self and other pain in the ACC and AI and then used them as seed regions for two kinds of functional connectivity analyses. These analyses identified areas whose activity co-varied with ACC and AI activity during self or other pain either across time (intra-individual connectivity) or across participants (inter-individual connectivity). Both connectivity analyses identified clusters in the midbrain and periaqueductal gray with greater connectivity to the AI during self pain as opposed to other pain. The opposite pattern was found in the dorsal medial prefrontal cortex, that showed greater connectivity to the ACC and AI during other pain than during self pain using both types of analysis. Intra-individual connectivity analyses also revealed regions in the superior temporal sulcus, posterior cingulate, and precuneus that became more connected to ACC during other pain as compared to self pain. Together, these data demonstrated that regions showing similar activity during self and other pain may nonetheless be part of distinct functional networks. These networks could not have been detected in prior work that examined overlap between self and other pain in terms of average activity, but not connectivity.

The Need for a Cognitive Neuroscience of Naturalistic Social Cognition

Understanding the minds of others is one of the great challenges humans face. Accordingly, much work in cognitive neuroscience has explored the brain systems engaged when perceivers share and make inferences about the internal states of social targets. These studies, however, typically use divergent and highly simplified stimuli and methods and as a consequence have produced largely non‐overlapping sets of results and artificially constrained theories about the processes involved in perceivers’ abilities to understand targets. Here we suggest that these difficulties may stem from two main sources: the lack of meaningful behavioral data about the brain bases of perceivers’ accuracy in inferring target states and qualitative differences between the social stimuli used in neuroimaging paradigms and the social information perceivers encounter in the real world. We advocate more focus on studies of naturalistic social cognition, which could overcome these limitations and complement current approaches, and discuss work in our laboratory that has demonstrated the feasibility and utility of such a focus. Finally, we discuss the relevance of naturalistic social cognition to diagnosing and treating autism spectrum disorder. Overall, using naturalistic paradigms in neuroimaging will be critical to modeling the way the brain actually understands other minds.

Equitable decision making is associated with neural markers of intrinsic value

Standard economic and evolutionary models assume that humans are fundamentally selfish. On this view, any acts of prosociality—such as cooperation, giving, and other forms of altruism—result from covert attempts to avoid social injunctions against selfishness. However, even in the absence of social pressure, individuals routinely forego personal gain to share resources with others. Such anomalous giving cannot be accounted for by standard models of social behavior. Recent observations have suggested that, instead, prosocial behavior may reflect an intrinsic value placed on social ideals such as equity and charity. Here, we show that, consistent with this alternative account, making equitable interpersonal decisions engaged neural structures involved in computing subjective value, even when doing so required foregoing material resources. By contrast, making inequitable decisions produced activity in the anterior insula, a region linked to the experience of subjective disutility. Moreover, inequity-related insula response predicted individuals’ unwillingness to make inequitable choices. Together, these data suggest that prosocial behavior is not simply a response to external pressure, but instead represents an intrinsic, and intrinsically social, class of reward.

Reintegrating the Study of Accuracy Into Social Cognition Research

Understanding the contents of other minds is a vital and ubiquitous task that humans perform with impressive skill. As such, it is surprising that the majority of social cognition research—whether behavioral or neuroscientific—focuses on the processes people use when attempting to understand each other while ignoring how well those attempts fare. Here we review historical reasons for the contemporary dominance of process-oriented research as well as the resurgence in the last decades of new approaches to studying interpersonal accuracy. Although in principle both the accuracy-oriented and process-oriented approaches study related aspects of the same phenomena, in practice they have made strikingly little contact with each other. We argue that integrating these approaches could expand our understanding of social cognition, both by suggesting new ways to synthesize extant data and generate novel predictions and lines of research, and by providing a framework for accomplishing such an integration. This integration can be especially useful in highlighting the deeply contextualized nature of the relationships between social cognitive processes, accuracy, and adaptive social behavior.

Common and distinct neural correlates of personal and vicarious reward: A quantitative meta-analysis

Individuals experience reward not only when directly receiving positive outcomes (e.g., food or money), but also when observing others receive such outcomes. This latter phenomenon, known as vicarious reward, is a perennial topic of interest among psychologists and economists. More recently, neuroscientists have begun exploring the neuroanatomy underlying vicarious reward. Here we present a quantitative whole-brain meta-analysis of this emerging literature. We identified 25 functional neuroimaging studies that included contrasts between vicarious reward and a neutral control, and subjected these contrasts to an activation likelihood estimate (ALE) meta-analysis. This analysis revealed a consistent pattern of activation across studies, spanning structures typically associated with the computation of value (especially ventromedial prefrontal cortex) and mentalizing (including dorsomedial prefrontal cortex and superior temporal sulcus). We further quantitatively compared this activation pattern to activation foci from a previous meta-analysis of personal reward. Conjunction analyses yielded overlapping VMPFC activity in response to personal and vicarious reward. Contrast analyses identified preferential engagement of the nucleus accumbens in response to personal as compared to vicarious reward, and in mentalizing-related structures in response to vicarious as compared to personal reward. These data shed light on the common and unique components of the reward that individuals experience directly and through their social connections.