The willingness to incur personal costs to enforce prosocial norms represents a hallmark of human civilization. Although recent neuroscience studies have used the ultimatum game to understand the neuropsychological mechanisms that underlie the enforcement of fairness norms; however, a precise characterization of the neural systems underlying fairness-related norm enforcement remains elusive. In this study, we used a coordinate-based meta-analysis on functional magnetic resonance imaging (fMRI) studies using the ultimatum game with the goal to provide an additional level of evidence for the refinement of the underlying neural architecture of this human puzzling behavior. Our results demonstrated a convergence of reported activation foci in brain networks associated with psychological components of fairness-related normative decision making, presumably reflecting a reflexive and intuitive system (System 1) and a reflective and deliberate system (System 2). System 1 (anterior insula, ventromedial prefrontal cortex [PFC]) may be associated with the reflexive and intuitive responses to norm violations, representing a motivation to punish norm violators. Those intuitive responses conflict with economic self-interest, encoded in the dorsal anterior cingulate cortex (ACC), which may engage cognitive control from a reflective and deliberate System 2 to resolve the conflict by either suppressing (ventrolateral PFC, dorsomedial PFC, left dorsolateral PFC, and rostral ACC) the intuitive responses or over-riding self-interest (right dorsolateral PFC). Taken together, we suggest that fairness-related norm enforcement recruits an intuitive system for rapid evaluation of norm violations and a deliberate system for integrating both social norms and self-interest to regulate the intuitive system in favor of more flexible decision making.

Recent research has examined the effects of oxytocin (OT) and vasopressin (AVP) on human social behavior and brain function. However, most participants have been male, while previous research in our lab demonstrated sexually differentiated effects of OT and AVP on the neural response to reciprocated cooperation. Here we extend our previous work by significantly increasing the number of participants to enable the use of more stringent statistical thresholds that permit more precise localization of OT and AVP effects in the brain. In a double-blind, placebo-controlled study, 153 men and 151 women were randomized to receive 24 IU intranasal OT, 20 IU intranasal AVP or placebo. Afterwards, they were imaged with fMRI while playing an iterated Prisoner's Dilemma Game with same-sex partners. Sex differences were observed for effects of OT on the neural response to reciprocated cooperation, such that OT increased the caduate/putamen response among males, whereas it decreased this response among females. Thus, 24 IU OT may increase the reward or salience of positive social interactions among men, while decreasing their reward or salience among women. Similar sex differences were also observed for AVP effects within bilateral insula and right supramarginal gyrus when a more liberal statistical threshold was employed. While our findings support previous suggestions that exogenous nonapeptides may be effective treatments for disorders such as depression and autism spectrum disorder, they caution against uniformly extending such treatments to men and women alike.

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