Yayuan Geng

Oxytocin, the peptide that bonds the sexes also divides them

Significance To interpret and respond appropriately to social cues is a fundamental aspect of human nature that becomes impaired in many mental disorders. The past decade has witnessed unprecedented excitement across neuroscience, psychology, and psychiatry regarding the role of oxytocin in human social cognition and its potential therapeutic use. There is also a considerable long-established public interest in behavioral sex differences and the molecular and brain mechanisms responsible. The current findings provide the first mechanistic explanation, to our knowledge, for how this key social molecule has evolved sex-dependent actions on amygdala function to influence the salience and attractiveness of positive social attributes in women but negative ones in men. Facilitation of social attraction and bonding by the evolutionarily conserved neuropeptide oxytocin is well-established in female mammals. However, accumulating behavioral evidence suggests that oxytocin may have evolved sex-specific functional roles in the domain of human social cognition. A critical question is how oxytocin differentially modulates neural processing of social information in men and women, leading to divergent behavioral responses. Here we show that intranasal oxytocin treatment produces sex- and valence-dependent increases in amygdala activation when women view individuals identified as praising others but in men those who criticize them. Women subsequently show increased liking for the faces of these individuals, whereas in men it is reduced. Thus, oxytocin may act differentially via the amygdala to enhance the salience of positive social attributes in women but negative ones in men. We hypothesize that oxytocin may have evolved different but complementary roles to help ensure successful reproduction by encouraging mothers to promote a prosocial rearing environment for offspring and fathers to protect against antisocial influences.

Oxytocin makes females, but not males, less forgiving following betrayal of trust

Although oxytocin has been shown to enhance trust behavior, to date no study has directly established whether oxytocin can modulate the effect of repair strategies on restoring damaged trust. In the current double-blind, between-subjects, placebo-controlled design study, two repair strategies were used to examine the effect of intranasal oxytocin administration on modulating trust restoration in a revised trust game. The results showed that although oxytocin had no overall effect on modulating trust restoration, it did have a significant gender specific effect. Female subjects showed less evidence for trust repair in the oxytocin compared with the placebo treatment group. This suggests that oxytocin may make female subjects exhibit more punitive behavior towards partners who violate their trust and less sensitive to repair strategies provided by them. Interestingly, this gender specific effect was more evident in the context of attempted trust repair using financial compensation. However, it also extended to both apology alone and no compensation conditions, but not to the fair one, in females exhibiting high trait forgiveness. Thus females with a more forgiving attitude towards betrayal may actually be more likely to punish betrayal following oxytocin treatment.

Oxytocin increases liking for a country's people and national flag but not for other cultural symbols or consumer products.

The neuropeptide oxytocin enhances in-group favoritism and ethnocentrism in males. However, whether such effects also occur in women and extend to national symbols and companies/consumer products is unclear. In a between-subject, double-blind placebo controlled experiment we have investigated the effect of intranasal oxytocin on likeability and arousal ratings given by 51 adult Chinese males and females for pictures depicting people or national symbols/consumer products from both strong and weak in-groups (China and Taiwan) and corresponding out-groups (Japan and South Korea). To assess duration of treatment effects subjects were also re-tested after 1 week. Results showed that although oxytocin selectively increased the bias for overall liking for Chinese social stimuli and the national flag, it had no effect on the similar bias toward other Chinese cultural symbols, companies, and consumer products. This enhanced bias was maintained 1 week after treatment. No overall oxytocin effects were found for Taiwanese, Japanese, or South Korean pictures. Our findings show for the first time that oxytocin increases liking for a nations society and flag in both men and women, but not that for other cultural symbols or companies/consumer products.

Oxytocin blurs the self‐other distinction during trait judgments and reduces medial prefrontal cortex responses

The neuropeptide oxytocin (OXT) may act either to increase or blur the distinction between self and other and thereby promote either more selfish or altruistic behaviors. To attempt to distinguish between these two possibilities we performed a double‐blind, between‐subject, placebo‐controlled design study to investigate the effect of intranasal OXT on self and other (mother, classmate, or stranger) trait judgments in conjunction with functional magnetic resonance imaging. Results showed that OXT reduced response times for making both self and other judgments, but also reduced the accuracy of their subsequent recall, thereby abolishing the normal self‐bias observed in this task. OXT also abolished the positive correlation between response and self‐esteem scale scores seen in the PLC group, suggesting that its effects were strongest in individuals with higher levels of self‐esteem. A whole‐brain functional magnetic resonance imaging analysis revealed that OXT also reduced responses during both self and other trait judgments in the dorsal (dmPFC) and ventral (vmPFC) medial prefrontal cortex. A subsequent region of interest analysis revealed that behavioral performance and self‐esteem scale scores were associated with dmPFC activation and its functional connectivity with the anterior cingulate and between the vmPFC and posterior cingulate. Thus overall, while OXT may improve speed of decision making in self ‐vs. other trait judgments it also blunts the normal bias towards remembering self‐attributes and reduces mPFC responses and connectivity with other cortical midline regions involved in self‐processing. This is consistent with the view that OXT can reduce self‐centered behavior. Hum Brain Mapp 37:2512–2527, 2016.

Sex-dependent neural effect of oxytocin during subliminal processing of negative emotion faces

&NA; In line with animal models indicating sexually dimorphic effects of oxytocin (OXT) on social‐emotional processing, a growing number of OXT‐administration studies in humans have also reported sex‐dependent effects during social information processing. To explore whether sex‐dependent effects already occur during early, subliminal, processing stages the present pharmacological fMRI‐study combined the intranasal‐application of either OXT or placebo (n = 86–43 males) with a backward‐masking emotional face paradigm. Results showed that while OXT suppressed inferior frontal gyrus, dorsal anterior cingulate and anterior insula responses to threatening face stimuli in men it increased them in women. In women increased anterior cingulate reactivity during subliminal threat processing was also positively associated with trait anxiety. On the network level, sex‐dependent effects were observed on amygdala, anterior cingulate and inferior frontal gyrus functional connectivity that were mainly driven by reduced coupling in women following OXT. Our findings demonstrate that OXT produces sex‐dependent effects even at the early stages of social‐emotional processing, and suggest that while it attenuates neural responses to threatening social stimuli in men it increases them in women. Thus in a therapeutic context OXT may potentially produce different effects on anxiety disorders in men and women. HighlightsOxytocin (OXT) induced sex‐dependent effect on BOLD level and functional connectivity.OXT decreased neural responses to negative faces in men but increased them in women.Increased ACC activity after OXT was positively linked with trait anxiety in women.OXT decreased functional connectivity in women.Sex might be an important factor moderating the putative anxiolytic effects of OXT.

Voluntary control of anterior insula and its functional connections is feedback-independent and increases pain empathy.

Real-time functional magnetic resonance imaging (rtfMRI)-assisted neurofeedback (NF) training allows subjects to acquire volitional control over regional brain activity. Emerging evidence suggests its potential clinical utility as an effective non-invasive treatment approach in mental disorders. The therapeutic potential of rtfMRI-NF training depends critically upon whether: (1) acquired self-regulation produces functionally relevant changes at behavioral and brain network levels and (2) training effects can be maintained in the absence of feedback. To address these key questions, the present study combined rtfMRI-NF training for acquiring volitional anterior insula (AI) regulation with a sham-controlled between-subject design. The functional relevance of acquired AI control was assessed using both behavioral (pain empathy) and neural (activity, functional connectivity) indices. Maintenance of training effects in the absence of feedback was assessed two days later. During successful acquisition of volitional AI up-regulation subjects exhibited stronger empathic responses, increased AI-prefrontal coupling in circuits involved in learning and emotion regulation and increased resting state connectivity within AI-centered empathy networks. At follow-up both self-regulation and increased connectivity in empathy networks were fully maintained, although without further increases in empathy ratings. Overall these findings support the potential clinical application of rtfMRI-NF for inducing functionally relevant and lasting changes in emotional brain circuitry.

Oxytocin Modulates Attention Switching Between Interoceptive Signals and External Social Cues

Emotional experience involves an integrated interplay between processing of external emotional cues and interoceptive feedback, and this is impaired in a number of emotional disorders. The neuropeptide oxytocin (OT) enhances the salience of external social cues but its influence on interoception is unknown. The present pharmaco-fMRI study therefore investigated whether OT enhances interoceptive awareness and if it influences the interplay between interoceptive and salience processing. In a randomized, double-blind, between-subject, design study 83 subjects received either intranasal OT or placebo. In Experiment 1, subjects performed a heartbeat detection task alone, while in Experiment 2 they did so while viewing both neutral and emotional face stimuli. Interoceptive accuracy and neural responses in interoceptive and salience networks were measured. In Experiment 1, OT had no significant influence on interoceptive accuracy or associated activity in the right anterior insula (AI) and dorsal anterior cingulate cortex. However, in Experiment 2 when face stimuli were also presented, OT decreased interoceptive accuracy and increased right AI activation and its functional connectivity with the left posterior insula (PI), with the latter both being negatively correlated with accuracy scores. The present study provides the first evidence that while OT does not influence processing of interoceptive cues per se it may switch attention away from them towards external salient social cues by enhancing right AI responses and its control over the PI. Thus OT may help regulate the interplay between interoceptive and external salience processing within the insula and could be of potential therapeutic benefit for emotional disorders.

Oxytocin biases men but not women to restore social connections with individuals who socially exclude them

We normally react to individuals who exclude us socially by either avoiding them or increasing our attempts to interact with them. The neuropeptide oxytocin can promote social bonds and reduce social conflict and we therefore investigated whether it facilitates more positive social responses towards individuals who exclude or include us. In a double-blind, placebo-controlled, between-subject design 77 healthy Chinese male and female participants received intranasal oxytocin (40 IU) or placebo before playing a modified virtual ball-tossing game with three fictitious partners who either showed exclusion, inclusion or neutral behavioral interactions with them. Results showed that both male and female subjects threw the ball more often to individuals who excluded rather than included them, although oxytocin did not alter this or awareness/feelings of exclusion or inclusion. However, when subjects returned a week later males, but not females, in the oxytocin group exhibited an increased liking for, and preference for playing again with, players who had previously excluded them. This oxytocin effect was positively associated with independent traits. Our findings suggest that in a collectivist culture oxytocin may promote the desire of males, but not females, with a stronger independent orientation to rebuild social connections with individuals who have previously excluded them.

Oxytocin Increases the Perceived Value of Both Self- and Other-Owned Items and Alters Medial Prefrontal Cortex Activity in an Endowment Task

The neuropeptide oxytocin (OXT) can influence self-processing and may help motivate us to value the attributes of others in a more self-like manner by reducing medial prefrontal cortex (mPFC) responses. We do not know however whether this OXT effect extends to possessions. We tend to place a higher monetary value on specific objects that belong to us compared to others, known as the “endowment effect”. In two double-blind, between-subject placebo (PLC) controlled experiments in subjects from a collectivist culture, we investigated the influence of intranasal OXT on the endowment effect, with the second study incorporating functional magnetic resonance imaging (fMRI). In the task, subjects decided whether to buy or sell their own or others’ (mother/father/classmate/stranger) possessions at various prices. Both experiments demonstrated an endowment effect in the self-owned condition which extended to close others (mother/father) and OXT increased this for self and all other-owned items. This OXT effect was associated with reduced activity in the ventral mPFC (vmPFC) in the self-owned condition but increased in the mother-condition. For the classmate- and stranger-owned conditions OXT increased activity in the dorsal mPFC (dmPFC). Changes in vmPFC activation were associated with the size of the endowment effect for self- and mother-owned items. Functional connectivity between the dmPFC and ventral striatum (VStr) was reduced by OXT in self- and mother-owned conditions and between vmPFC and precuneus in the self-condition. Overall our results show that OXT enhances the endowment effect for both self- and other-owned items in Chinese subjects. This effect is associated with reduced mPFC activation in the self-condition but enhanced activation in all other-conditions and involves differential actions on both dorsal and ventral regions as well as functional connectivity with brain reward and other self-processing regions. Overall our findings suggest that OXT increases the perceived value of both self- and other-owned items by acting on neural circuitry involved in self-processing and reward.

Oxytocin Enhancement of Emotional Empathy: Generalization Across Cultures and Effects on Amygdala Activity

Accumulating evidence suggests that the neuropeptide oxytocin (OXT) can enhance empathy although it is unclear which specific behavioral and neural aspects are influenced, and whether the effects are modulated by culture, sex, and trait autism. Based on previous findings in Caucasian men, we hypothesized that a single intranasal dose of OXT would specifically enhance emotional empathy (EE) via modulatory effects on the amygdala in an Asian (Chinese) population and explored the modulatory role of sex and trait autism on the effects. We first conducted a double-blind, randomized between-subject design experiment using a modified version of the multifaceted empathy task to determine whether OXT’s facilitation of EE can be replicated in Chinese men (n = 60). To further explore neural mechanisms behind and potential sex differences, functional MRI and skin conductance measures were acquired in an independent experiment incorporating men and women (n = 72). OXT enhanced EE across experiments and sex, an effect that was accompanied by reduced amygdala activity and increased skin conductance responses. On the network level OXT enhanced functional coupling of the right amygdala with the insula and posterior cingulate cortex for positive valence stimuli but attenuated coupling for negative valence stimuli. The effect of OXT on amygdala functional connectivity with the insula was modulated by trait autism. Overall, our findings provide further support for the role of OXT in facilitating EE and demonstrate that effects are independent of culture and sex and involve modulatory effects on the amygdala and its interactions with other key empathy regions.