Regulation of Oxytocin on Empathy and Its Neural Mechanism

*Guangxin Yue*

### **Abstract**

Empathy is a multidimensional concept, including emotion and cognition. It plays a vital role in social communication, and it is very important for establishing harmonious relationships, trust, and mutual understanding. Empathy includes the ability to feel and understand the emotions of others, which can be learned and improved through various ways. Oxytocin is a neuropeptide, and its influence on social behavior and emotions has been widely studied. It is found that it can enhance emotional and cognitive empathy, as well as trust and cooperative behavior. Oxytocin acts on specific brain regions, such as the insula, amygdala, and reward circuitry, to modulate empathy-related neural processes. Oxytocin receptor gene polymorphisms are also related to empathy. Future research could explore the effect of oxytocin interventions on individuals with empathy deficiency, investigate the relationship between oxytocin receptor gene polymorphism and empathy neural networks, and study the neural mechanisms of the influence of other neurochemical substances (such as dopamine) affecting empathy. In addition, further study on empathy of typical developing individuals could provide valuable insights into the symptoms and causes of various diseases. Finally, promoting the practical application and value transformation of research results related to empathy is helpful to develop intelligent systems that can simulate human empathy and enhance human-computer interactions.

**Keywords:** empathy, oxytocin, social behavior, mental disorder, neurobiology

## **1. Introduction**

Traditionally, empathy refers to the ability to share someone else's feelings or experiences by imagining what it would be like to be in that person's situation. By sharing and understanding the feelings of others, it can accurately judge the behavior of others, help obtain environmental information and adapt to the environment, and carry out social exchanges. It has important biology and sociological significance for individuals. Empathy encompasses the ability to contemplate and vicariously share in the emotional life of others and is critical for social interaction. Empathy is a multidimensional construct, which includes cognitive and affective components. Emotional empathy refers to the affective response of feeling what another person is feeling or having a similar emotional reaction. Cognitive empathy refers to the mental process of taking the perspective of another person and imagining what they are thinking or feeling. In the absence of emotional empathy, cognitive empathy is able to understand what another person is feeling without necessarily experiencing the same emotions.

Empathy is an important skill for social interactions, as it helps to build rapport, trust, and mutual understanding. Empathy can also enhance moral reasoning, ethical decision-making, and pro-social behavior. Empathy can be learned and improved through various methods, such as reading fiction, engaging in role-playing, practicing mindfulness, and receiving feedback.

The multidimensional nature of empathy has nothing to do with a single neurobiological process. Functional neuroimaging studies have shown that different components of empathy are associated with several related but distinct brain processes, marked by co-activation between brain regions [1].

#### **1.1 The definition of empathy**

Empathy is a multidimensional paradigm, and there currently is a lack of scientific consensus on its definition [2]. The debate over the concept and definition of empathy reflects the different understandings of researchers on the nature of empathy. So far, the academic understanding of the nature of empathy mainly includes the following aspects:

Some scholars consider empathy to be an instinctive response or experience of another person's emotion, an emotional phenomenon [3]. Empathy is a feeling. When the empathic person is absorbed in the empathic object, the empathic object has the expressiveness and passively produces a feeling obtained by self-imitation. Empathy is defined as the empath's emotional response to the empath's current or imminent experience of an emotion and considers an emotional response that is inconsistent with the empath's experience to be empathy, called "differential empathy". However, others define empathy as an emotional response that is considered to be similar to the emotion of the empathic object.

From the cognitive perspective, empathy is considered to be the understanding of another person's emotions from a cognitive level [4]. Empathy focuses on the understanding of another person's emotions. It is more than the sharing of emotions. Empathy is the individual's intellectual understanding of the thoughts and feelings of others, and on this basis, a cognitive empathy scale has been developed [5]. While emphasizing the cognitive component of empathy, the social role that empathy points to is more prominent. It is believed that empathy is an individual's ability to make choices about the roles of others. By understanding others' evaluations and perceptions of the outside world and predicting their further reactions from their behaviors, they can adjust their own behaviors in order to adapt quickly to society and live better in it.

Gladstein's "two-component theory" has had the most profound impact on empathy research [6]. It is believed that empathy contains both emotional and cognitive components, only that the weight of each differs in different scenarios. Gladstein divides empathy into Emotion empathy and Cognitive empathy. Emotional empathy is used to refer to an individual's ability to respond to the emotions of others. Cognitive empathy expresses an individual's ability to cognitively adapt another person's perspective and assess the state of another person. Brain imaging techniques were used to study empathy in brain-injured patients, and the results showed that emotional empathy and cognitive empathy involve separate brain regions [7]. This result provides strong evidence to support the "two-component theory".

#### **1.2 The neural basis of empathy**

There is increasing evidence suggests that empathy for pain is underpinned by neural structures [8, 9]. In the early days of research, scholars mainly explored the

#### *Regulation of Oxytocin on Empathy and Its Neural Mechanism DOI: http://dx.doi.org/10.5772/intechopen.112743*

inherent mechanism of empathy from a cognitive level. It explains how the individual understands the emotions of others but has not explained how the individual share the emotions of others. With the advancement of medical technology, cognitive neurosciences introduce brain imaging technology into empathy research. Therefore, further deepening the research of empathy and neural mechanisms can reveal the neural basis of empathic processes and the factors that influence them.

Emotional empathy refers to the individual's experience and sharing of the emotional state of others. Studies have found that there is a "representation sharing" between individuals and others; that is, when the individual perceives the emotions or movements of others, the part that corresponds to the emotion or movement in the brain will be activated [10]. Performing sharing is considered to be the basis of empathy, which is closely related to emotional empathy [9]. In an experiment investigating olfactory empathy, researchers found that the forebrain insula region was activated when subjects smelled disgusting odors or watched videos of expressions of disgusting emotions Similar results exist in the field of nociceptive empathy research [11]. In a study of individuals receiving painful stimuli and observing others receiving painful stimuli, Singer et al. found that the anterior cingulate gyrus and anterior insula, which are responsible for emotional processing, were activated in both states in subjects [12]. The mirror neuron is a sensory-motor neuron. It is activated during both the observation and execution phases of an action [13]. Neuroscientists first identified mirror neurons in the F5 region of the premotor cortex of the rhesus monkey brain, which were activated either when the monkey performed a certain action or when they observed another similar action. In subsequent studies, researchers determined that similarly functioning brain regions exist in the human brain and called them "mirror neural systems". The discovery provides strong evidential support for representational sharing. It has also been shown that the activation of the mirror neural system is very significantly related to emotional empathy.

Representation sharing and mirror neurology explain the emotional contagion of empathy. However, emotional contagion is only the initial stage of empathy, as individuals experience similar or different emotions while being emotionally contagious to others. Emotional empathy therefore also involves the amygdala, which generates and regulates emotions. In summary, we believe that emotional empathy primarily involves the anterior insula, anterior cingulate gyrus, amygdala, and mirror neurology.

Cognitive empathy is often associated with psychological theory. Both encompass the individual's ability to understand the mental states of others and to predict their behavior accordingly, as well as to distinguish between the mental states of the self and others. Psychological theory activates mainly brain areas such as the medial prefrontal cortex, temporal pole, superior temporal sulcus, and temporoparietal junction. Schnell found that the medial prefrontal cortex, temporopolar region, temporoparietal junction, and limbic system are involved in understanding the emotional state of others [14]. The Shamay-Tsoory study on empathy in brain-injured patients showed that individuals with ventral medial prefrontal cortex injuries had poor cognitive empathy and normal emotional empathy, and those with inferior frontal gyrus injuries had poor emotional empathy and normal cognitive empathy [15].

In addition to this, the researchers found that mirror neurons, while involved in the sharing of representations, may also be involved in the understanding of the purpose and desires of others from a conscious level. Fan, Y summarized previous work and found that the dorsal anterior cingulate cortex, anterior cingulate cortex, supplementary motor areas, and bilateral insula were activated in numerous forms of empathy

research [16]. Therefore, these brain regions are referred to as the core brain regions of empathy. Among them, cognitive and emotional empathy both activated the anterior insula on the left side, whereas cognitive love activated the anterior cingulate gyrus.

## **2. Empathy and oxytocin**

Oxytocin is a nonapeptide secreted by the paraventricular and supraoptic nuclei of the hypothalamus and released in the brain and blood through the posterior lobe of the pituitary gland. It acts as a neurotransmitter and a hormone with central (amygdala, para-ventricular nucleus of the hypothalamus, hippocampus, and brain stem) and peripheral (heart, womb, and spinal cord) effects. The neuropeptide oxytocin has a solid reputation as a facilitator of social interactions. It has been shown to have various effects on our social behavior and emotions, such as increasing trust, generosity, and compassion.

Research has found that oxytocin can improve both cognitive and emotional empathy in different ways. For example, one study found that oxytocin administration increased the ability to recognize emotions in others and improved self-reported empathy [17]. Another study found that oxytocin increased the neural response to positive social feedback and reduced the neural response to negative social feedback [18]. This suggests that oxytocin can make us more sensitive to rewarding social cues and less sensitive to stressful social cues.

Studies have revealed oxytocin receptors are expressed pre- and postnatally, raising the possibility that developmental oxytocin signaling may have a lasting impact on brain organization and behavior. Oxytocin can modulate the neural activity associated with empathy in the brain. Studies have found that oxytocin can increase the activation of brain regions involved in empathy, such as the insula, the anterior cingulate cortex, and the amygdala [19]. Oxytocin can also reduce the activation of brain regions involved in self-referential processing, such as the medial prefrontal cortex, which may facilitate empathic understanding by reducing egocentric bias [20].

Oxytocin was initially thought to increase empathy for all. However, more careful research showed that although oxytocin increased empathy for in-group members, it had no affect or actually decreased empathy for out-group members [21]. A possible explanation for this behavior could be that oxytocin increases the salience of social stimuli [22]. Oxytocin does improve the ability to recognize facial emotions, but this also depends on the time and intensity of exposure [23]. More research on empathy suggests that oxytocin appears to enhance emotional empathy and has little effect on cognitive empathy [24, 25].

Research has shown, empathy is the basis for human social interaction [26]. It can help us build a trust, cooperation, empathy, and altruistic relationship. Emotional empathy can increase pro-social behavior, but this role is played with a certain degree of self-interest. When the level of personal distress in sympathizing with someone reaches a given threshold, individuals seem to gravitate toward their own feelings rather than using that distress as a motivation to help someone in need. Cognitive empathy is more conducive to pro-social behavior [27]. Pro-social behavior was marked by dorsomedial prefrontal cortex activity; this area is involved in mentalizing and helps individuals better understand the needs of others, thus enabling more altruistic behavior [27].

#### **2.1 The impact of oxytocin level on empathy response**

At present, there are two main areas of research investigating the effects of oxytocin on empathic responses. One is to examine the effect of individual endogenous oxytocin levels on the empathic response, and the other is to discuss the effect of exogenous oxytocin interventions on the empathic response.

Studies have found that the production of empathic experiences is accompanied by increased levels of oxytocin in the peripheral nervous system. By observing the empathy concern and the subjective level of individual sadness when watching short films (emotional or non-emotional), the relationship between it and plasma oxytocin level was determined. It was found that oxytocin levels in the subjects' blood were significantly higher when viewing emotional clips than nonemotional clips [28]. This suggests that the empathy experience of the individual will be accompanied by the release of the oxytocin in the brain. Interestingly, empathy-induced changes in oxytocin were associated with gender. Compared with men, the changes in oxytocin were stronger in women, and thus women's empathy is significantly higher than men's. Also, the concentration of oxytocin in an individual's blood can predict the intensity of the empathic response. During pregnancy, the mother's oxytocin level increases significantly, triggered by the rise in estrogen levels, and this increase continues into the breastfeeding period. In this process, the level of oxytocin release is strongly related to the mother's empathy [28]. Compared to mothers with low levels of oxytocin in the blood, mothers with high levels of oxytocin have stronger reward levels in the brain when they see their baby smiling. This activation suggested that they are more likely to resonate with their children's emotions [29]. In summary, there is a closely relationship between the level of endogenous oxytocin in an individual and the strength of the empathic response.

Existing neurological studies show that oxytocin ejected from the nasal cavity can directly cross the blood-brain barrier and act on the limbic systems closely related to social behavior, such as hippocampus and amygdala. By intervening with exogenous oxytocin, it is possible to directly regulate the level of oxytocin in the central nervous system and thus establish a causal relationship with society. Domes et al. were the first to report that oxytocin improved cognitive empathy ("mindreading"), as measured using the "Reading the Mind in the Eyes Test" (RMET). In the RMET, subjects were shown the eye area of different people and asked to assign one of four descriptive terms to the expression. Results found that intranasal oxytocin improved RMET performance. Another functional magnetic resonance imaging (fMRI) study investigating RMET performance depending on oxytocin Administration also detected increased insula activation (and superior temporal gyrus activation) after oxytocin administration and reproduced the oxytocin effect on RMET performance of the Domes group. Also, nasal inhalation of oxytocin directly affects the level of emotional response in empathy. However, some researchers have also found that nasal oxytocin has a significant effect on the empathy of individuals. By presenting four sad stories recording to the subjects and then recorded their empathy responses. They found that oxytocin injection increased the empathy level for the female protagonist in the story, but not for the male protagonist, regardless of the subjects' gender [30]. Thus, specifically, oxytocin can be effective in raising the level of empathic attention to the emotions of others. However, negative emotions directed toward the self due to the misfortune of others not only are not significantly enhanced but may also be weakened.

#### **2.2 Oxytocin affects empathy response mechanisms**

At present, the more recognized neural mechanism of empathy reflex is mirror neuroscience. More and more studies have found that oxytocin promotes the activity of individual mirror neurology. Oxytocin enhances the activity of mirror neurons to improve the individual's ability to imitate [31]. The fMRI was used to study the response of oxytocin in the brain of female subjects to neural network regulation of an infant crying. The results showed that injection of oxytocin weakened the activation in the right amygdala and enhanced activation of insula and inferior frontal gyrus (mirror neuron brain region). This suggests that when women perceive frightening social stimuli, oxytocin will reduce the activity of amygdala, prevent women from being distracted by anxiety or disgust, and thus promote their ability to respond to a baby's cries. At the same time, oxytocin may enhance women's empathy responses to a baby crying by enhancing the activation of brain regions (insula and inferior frontal gyrus) related to emotional empathy [32].

Oxytocin can act on the self-information processing system, weakening the self-centered tendencies of individual in social information processing and making it easier for people to shift their perspective and focus on the mental states and feelings of others [33]. A facial deformation program is used to explore the influence of oxytocin on self-others distinctions. The results of this study show that oxytocin lowers the threshold for distinguishing self from other people's faces in the experimental task and at the same time increases the perception of others' favor ability, which proves the effectiveness of oxytocin in overcoming individual self-service bias [20]. The essence of empathy is the experience of congruent emotions with the emotionproducing object. It is also found that oxytocin affects the emotional expression mechanisms of individuals, mainly by weakening negative emotions and promoting positive emotions. On the one hand, oxytocin reduces the level of amygdala activity in response to negative emotional faces (fear, anger, sadness and disgust, and physical pain) [34–37]. In addition to amygdala activity, oxytocin can also reduce the activity of other brain areas associated with negative affect, such as the anterior insula and anterior cingulate gyrus. Oxytocin may also increase activity in areas of the brain related to emotional management, such as the medial prefrontal lobe and ventrolateral prefrontal lobe. Overall, oxytocin may weaken individuals' negative emotional feelings and improve emotion management, which helps individuals reduce social anxiety and stress levels and promote positive social interactions. On the other hand, oxytocin can increase the level of activation of the reward system in social interactions. When the subjects watched positive social stimuli, such as happy faces or photos of their partners and children or participating in positive social interaction, oxytocin was found to be significantly enhanced in other brain regions of the reward system, such as the ventral segment, the nucleus accumbens, the caudate nucleus, the vomeronasal nucleus, and the midbrain [38–40]. These findings suggest that oxytocin increases the value of rewards in social contexts, enhances interpersonal connections, and strengthens social relationships.

#### **2.3 Oxytocin regulates pro-social behavior by affecting empathy**

Pro-social behavior is a common aspect of individual socialization, and it plays a vital role in individual social development. In fact, the term "pro-social behavior" was first introduced by American scholar Wispel, who contrasted it with antisocial behavior such as vandalism and aggression. According to social psychologists,

#### *Regulation of Oxytocin on Empathy and Its Neural Mechanism DOI: http://dx.doi.org/10.5772/intechopen.112743*

pro-social behavior aligns with social moral standards, whereas antisocial behavior violates them. Initially, pro-social behavior refers to adherence to social rules and moral standards. It involves voluntary actions that individuals take to benefit others, the community, or society as a whole, including acts of cooperation, assistance, sharing, donation, and compassion, among others. Such behaviors are subject to the constraints of social moral standards. There are two types of pro-social behavior, categorized according to the situation. Pro-social behavior in emergency situations involves acts of courage, such as saving lives during water or fire emergencies, while pro-social behavior in non-emergency situations entails helping others without harm or threat to the person performing the behavior. Pro-social behavior can be motivated by two different factors. Completely pro-social behavior occurs when individuals help others without any conscious pursuit of personal benefit. Conversely, partial prosocial behavior involves individuals helping others with the expectation of receiving help in return. The social heuristic hypothesis suggests that pro-social behaviors become internalized as default heuristics in an individual's daily life, leading to the development of automatic pro-social behavioral tendencies. Ultimately, pro-social behavior is an essential aspect of individual socialization and development, and it plays a crucial role in maintaining social cohesion and stability.

Batson proposed the empathy-altruism hypothesis, which suggests that prosocial behavior motivated by empathy aims to provide welfare to those in need [41]. Several scholars have provided evidence that empathy is the biological foundation of pro-social behavior, altruism, and morality. The empathy-altruism hypothesis predicts that empathically aroused individuals will experience empathic joy when they learn that the needs of others have been met, but this joy is a consequence of their helping to address the needs of others and is not an end in itself. Empathy not only has an altruistic effect; it can also have an egoistic effect. Empathic emotions can be unpleasant, and individuals can reduce the experience of discomfort by engaging in pro-social behavior. Studies related to pro-social behavior have demonstrated that empathy is a vital factor that influences pro-social behavior. Empathy enables people to understand the feelings and needs of others, which can motivate individuals to exhibit more pro-social behaviors.

Oxytocin is believed to be closely related to empathy and is also one of the most extensively studied hormones. Pregnant women have the effect of promoting uterine contractions during childbirth and lactation after childbirth. In addition, the establishment of mother-child attachment relationships related to empathy, children playing together, making friends, spouses, and erections during sexual activity all require oxytocin. Therefore, some scholars suggest calling it "empathy". Because oxytocin can be sprayed through the nasal mucosa and enter the cerebrospinal fluid through the olfactory filament to act on sympathetic brain regions, it can also promote the release of oxytocin from oxytocin neurons in the paraventricular nucleus and supraoptic nucleus of the hypothalamus into the circulating blood through the posterior pituitary, playing a "social" hormone role. Literature shows that nasal spraying of oxytocin can enhance social skills such as pain empathy, mother-child attachment, social cognition, and facial recognition, enhancing empathy within groups, integrity, collaboration, conformity, and resistance to attacks outside of groups.

#### *2.3.1 Oxytocin and face perception*

Numerous studies have demonstrated that oxytocin can impact face recognition abilities. Specifically, oxytocin has been found to have a significant effect on individuals' ability to recognize basic emotions. In a study by Lischke et al., participants from both the oxytocin and placebo groups were given dynamic facial expression recognition tasks involving four emotions—joy, anger, sadness, and fear—with varying levels of emotional intensity [42]. The results indicated that the oxytocin group had a more accurate recognition of all emotions, especially recognizing lower intensity facial expressions, compared to the placebo group.

Additionally, some clinical studies have suggested that oxytocin might improve emotional recognition ability in patients with certain mental disorders. For instance, exogenous oxytocin attenuates early attentional biases toward negative stimuli and increases selective attention and recognition of emotional cues in faces, particularly around the eyes [43]. However, some studies have shown that the impact of oxytocin on emotional recognition is regulated by the emotional valence, meaning that it enhances recognition of positive emotions while reducing recognition of negative emotions. For instance, Domes instructed male participants to focus on emotional faces and found that oxytocin increased the frequency of gaze on positive faces (happy) but decreased the frequency on negative faces (angry) [44]. Woolley et al. found that oxytocin can improve facial recognition ability but cannot improve interpersonal trust [45]. While oxytocin appears to have a positive effect on the recognition of certain emotions, further research is needed to confirm these findings.

#### *2.3.2 Oxytocin and emotional inference*

Emotional inference refers to people's ability to understand and perceive the emotional state of others in social interactions. When we communicate with others, we usually infer their emotional state through nonverbal signals such as facial expressions, language intonation, and body language, such as joy, sadness, and anger. This ability is crucial for establishing and maintaining social interaction and interpersonal relationships. Emotional inference includes not only the perception of the emotional state of others but also the understanding and inference of their emotional state. For example, when we see a person smiling, we can not only perceive that their emotional state is positive but also infer that they may be smiling due to reasons such as happiness, satisfaction, and gratitude. Emotional inference is an advanced cognitive function, which involves the synergy of multiple brain regions, including the visual cortex, amygdala, prefrontal cortex, and so on. In daily life, emotional inference ability significantly impacts people's social and emotional health. Some social and emotional disorders, such as autism and depression, are related to insufficient emotional inference ability. Therefore, improving emotional inference ability is of great significance for improving social and emotional disorders.

Observing basic emotional information such as facial expressions, speech, and actions can trigger an individual's emotional experiences due to a process called emotional resonance. The Perception-Action Model (PAM) of empathy proposes that when someone perceives sensory emotional information, they unconsciously engage in an action imitation process that activates the mirror neuron system. This system includes brain areas such as the parietal and inferior lobules, inferior frontal gyrus, and anterior motor cortex, which enable the perceiver to feel the perceived emotion through physiological feedback [46].

Similarly, Walter's Empathy Loop Model suggests that individuals must infer and understand others' psychological states to resonate emotionally with them [47]. This process activates the ventromedial prefrontal lobe and enables emotional resonance with the other person. Thus, individuals who are better at taking the perspective of

#### *Regulation of Oxytocin on Empathy and Its Neural Mechanism DOI: http://dx.doi.org/10.5772/intechopen.112743*

others are more capable of projecting themselves into others' psychological states and sharing their emotions. Those who struggle to overcome their egocentric tendency may find it challenging to empathize with others [48]. Overall, emotional resonance is a complex and embodied process that involves both physiological and cognitive mechanisms.

Empathic reactions can lead to the development of empathy concerns toward others, resulting in positive emotions such as love, care, and other motivational factors that promote pro-social behavior. This positive attention to others' misfortunes is an essential psychological factor that fosters empathy and pro-social behavior.

Researchers have found that oxytocin can enhance an individual's ability to infer others' emotions, as demonstrated through experimental paradigms such as the RMET and viewpoint-taking tasks. For instance, Domes discovered that oxytocin administration through nasal injection improved male participants' theory-of-mind abilities in the RMET [49]. The task requires participants to infer the psychological state of individuals based solely on their eye area in a photograph, and oxytocin improved accuracy, particularly in more challenging tasks [24].

In summary, oxytocin has a positive impact on emotional inference. This discovery helps us better understand the role of oxytocin in social behavior and emotions and provides a more in-depth research direction for future research.

#### *2.3.3 Oxytocin and trusting and cooperative behavior*

Oxytocin also has the ability to influence trusting and cooperative behaviors, thereby facilitating social interactions and building strong interpersonal relationships. The neural mechanisms underlying cooperative and protective behavior, as an important function of human survival, have always been a focus of discussion among researchers. Related research has found that compared to making non cooperative choices, when individuals make cooperative choices that require loss of their own interests but result in greater benefits for the team, oxytocin group participants tend to choose more cooperative options [50, 51], which means that oxytocin makes individuals more willing to sacrifice their own interests to promote cooperative behavior. More options have been chosen for noncooperation to ensure that members of the inner group are not attacked.

The Trust Game is a widely used research paradigm for investigating human trust behavior, with investment amount and frequency serving as key indicators. In a pioneering study, Kosfeld et al. administered nasal spray oxytocin and found that it increased investment behavior and trust tendencies in individuals, demonstrating the influence of oxytocin on trust behavior [52]. However, subsequent studies indicate that the trustworthiness of the trustee can affect the effectiveness of oxytocin, with oxytocin enhancing trust behavior only toward trustworthy trustees [53]. Moreover, oxytocin seems to affect men and women differently, as it causes women to exhibit less trust and forgiveness toward betraying trustees than men [54]. Additionally, personality traits play a crucial role in determining trust behavior, with oxytocin causing individuals with borderline personality disorder (BDP) to exhibit less trust [55].

Apart from trust games, researchers have explored the impact of oxytocin on trust behavior in other paradigms. In one study, participants evaluated strangers' photos to measure trust levels, and the oxytocin group displayed higher trust scores and was rated as more attractive than the placebo group [56]. Moreover, pupil contraction in trustees can affect an individual's trust level, with oxytocin reducing trust in pupillary contraction partners but increasing trust in pupillary dilation partners [57]. Long-term (two-week) intranasal administration of oxytocin has also been found to reduce avoidant attachment and increase attachment to peers, making participants more inclined to trust others [58]. Neuroimaging studies provide further evidence for the mechanism by which oxytocin impacts trust behavior. In functional magnetic resonance imaging (fMRI) research, oxytocin reduced the activation of the striatum, amygdala, and midbrain regions after betrayal, indicating less fear processing and behavior adjustment based on feedback information and thus more trust behavior [59]. Additionally, oxytocin promotes mutually beneficial cooperative behavior by increasing the value of individuals' rewards and forming the belief that others are trustworthy, as observed in stronger caudate nucleus activation in the oxytocin group during cooperation [60].

While many studies have shown that oxytocin enhances trust behavior, replicating these results can be challenging due to factors such as variation in experimental design and procedures. A meta-analysis did not find any significant effect of nasal administration of oxytocin on trust behavior [61]. This suggests that further research is needed to replicate and validate the experimental effects of oxytocin on trust behavior in the future.

#### *2.3.4 Oxytocin and group preference*

Group preference, also known as herding behavior or social assimilation, is the tendency for people to accept the ideas, values, and behaviors of a group when they are in that group, rather than pursuing their own unique ideas and behaviors. This phenomenon occurs in a variety of different groups, such as families, schools, workplaces, social media, and so forth. It usually occurs when people want to gain social acceptance and group approval or avoid social exclusion. When people feel different or isolated from others, they usually try to adjust their behaviors and thoughts to conform to the group's expectations and standards. Current research suggests that oxytocin can influence group preferences, making it easier for people to accept and follow group expectations and behavioral norms.

Variations of the Prisoner's Dilemma task have been used by researchers to investigate cooperative and protective behavior, and the results indicate that the oxytocin group exhibited greater love for inner group members and lower selfishness but did not show any impact on their hatred toward outer group members [62]. Interestingly, oxytocin did not display the same tendency as aggressionenhancing hormones toward members outside the group. In the Prisoner's Dilemma task, De Dreu found that individuals in the oxytocin group were more likely to choose not to cooperate with external group members to ensure their higher interests, resulting in lower profits for internal group members in a "predatory" state [62]. Furthermore, in situations of "greed," where individuals choose not to cooperate to improve their own interests and reduce the profits of members outside the group, the oxytocin group did not increase the number of noncooperative choices to demonstrate "plundering" of members outside the group. This suggests that oxytocin promotes the protection of more vulnerable internal group members, rather than attacking external group members. This further supports the idea that oxytocin promotes love for members within the group, rather than hatred for members outside the group.

Similarly, additional studies that added cognitive load to the Prisoner's Dilemma task found that oxytocin promotes cooperative behavior without the influence of cognitive load. The placebo group, on the other hand, exhibited more cooperative behavior only when there was cognitive load. These results suggest that the love for

members of the inner group induced by oxytocin is inherent and intuitive, rather than intentional [63].

However, subsequent studies have found a "dark side" to oxytocin, such as an increase in distrustful [64] and deceptive [65] decision-making behaviors, suggesting that oxytocin does not always promote pro-social behavior and that the factors influencing it have attracted the attention of researchers.

#### **2.4 Oxytocin, social cognition, and neural circuits patterns**

The effects of oxytocin on individual social cognition may be achieved mainly through modulating the activation patterns of the amygdala and reward system [66, 67]. Specifically, oxytocin weakens the amygdala response to negative emotional information and increases its functional connectivity to brain regions involved in emotion management. Experimental studies have found that the administration of intranasal oxytocin reduces amygdala activation after subjects are confronted with fearful faces and disgusting scenes. Similarly, in the fMRI paradigm study, the amygdala showed an increased responsiveness to the fearful whites of the eyes. However, this response was diminished when oxytocin was given prior to testing [35]. Interestingly, when different stimuli are presented, oxytocin appears to not only reduce amygdala activation but also facilitate insula responses, thus making negative stimuli easier to remember [68].

Oxytocin is closely associated with the reward neural circuit, which is concentrated in the midbrain, including the ventral tegmental area (VTA) and the basal ganglia, which contains the globus pallidus (GP), the substantia nigra (SN), the ventral striatum (VS), and the dorsal striatum, which contains the putamen and caudate, areas that are essential for reward processing. When cooperative behavior in a Prisoner Dilemma game was reciprocated, oxytocin augmented caudate nucleus activation in addition to the amygdala response. Oxytocin acts in these brain areas above to increase reward and emergence in interpersonal interactions (face processing, cooperation, romance, parenting, etc.), thus promoting social bonding and attachment.

#### **2.5 Oxytocin receptor and empathy disorder**

Oxytocin receptor is widely expressed in mammalian brains, including the septum, nucleus accumbens, and ventral tegmental area. Research finds a correlation between the oxytocin receptor gene and psychopathy traits, suggesting that the oxytocin gene can affect the brain's empathy response [69].

The oxytocin receptor gene, which is located on chromosome 3p25.3, has been implicated as a candidate gene for susceptibility of autism spectrum disorder (ASD) [70]. ASD is a representative disorder of pervasive developmental disorders, which affect the development of social, communication, and behavioral skills. Its core symptoms are: impaired social interaction, communication difficulties, narrow interests, and stereotypical repetitive behavior patterns. Psychologists generally agree that autism is the result of a combination of genetics and environment. However, in recent years, the emerging empathic-systemic theory has explained the onset of autism in a more comprehensive way. Children with autism have difficulty recognizing facial expressions, have a lower ability to recognize the emotions of others, and have a lower level of development in naming and matching expressions than normal children. This can lead to difficulties in accurately perceiving the emotions of others or biases in their perception of the emotions of others, resulting in deficits in empathy.

Experiments have shown that children with autism have lower plasma oxytocin levels than healthy children of the same age and that elevated oxytocin levels do not correlate positively with increasing age of the child. Lower levels of endogenous oxytocin are arousing in children with ASD, but not in adolescents or adults [71]. Anyway, oxytocin is generally considered to be associated with social deficits in ASD.

Similarly, animal experiments have shown that oxytocin receptor knockout mice exhibit behavioral deficits associated with autism and that exogenous oxytocin supplementation ameliorates this deficit [72, 73]. Autism is associated with mutations in genes such as the gene encoding contact-related protein-like protein 2 (Cntnap2). Intraperitoneal or intranasal administration of oxytocin ameliorates social behavioral deficits in mice with null mutations in the Cntnap2 gene. The use of drugs to promote the release of endogenous oxytocin can stimulate the oxytocin system more effectively and improve socially abnormal behavior.
