[1] Neural substrates underlying the elementary processes of social skills that arise during development

(1) Self-face recognition

A human infants start to recognize their own faces in mirrors at the age of 18–24 months (visual self-recognition). By the age of 3–4 years, they start evaluating their appearances or behaviors, and experiencing self-conscious emotions such as shame (self-rating). We used fMRI to investigate the neural structures underlying self-conscious emotional reactions generated during self-face processing. In this experiment, subjects were provided with photographs of strangers or themselves, and then scanned while evaluating how the people in the photos looked. We found that self-concern and self-rating have independent neural substrates in the right frontal area. On the other hand, it has been proposed that individuals with autistic spectrum disorders (ASD) do not experience such self-conscious emotions. We conducted the same experiment in normal adults and adults with high-functioning ASD. The normal group exhibited a strong negative correlation between their ratings of their own photos and the intensity of shame-related feelings, whereas the ASD group exhibited a weaker correlation between them. This observation indicates that people with ASD have a weak association between cognitive rating of self-face and emotional reactions. In the ASD group, the activity related to self in the posterior cingulate gyrus was lower than that in the normal group, and the degree of the decrease was related to the severity of autism. Furthermore, task-related activity in the right insular cortex was generally lowered throughout the ASD group. In particular, the reduction in activity related to their own faces was correlated with the weakness of the association between the evaluation score of their own photo and the score of shame-related feelings. From these results, we concluded that the lack of self-conscious emotion observed in persons with ASD results from dysfunction of the posterior cingulate gyrus, which is responsible for the process of internal information about themselves, as well as dysfunction of the right insular cortex, which is responsible for various emotional experiences (Morita et al. 2012). This understanding was confirmed by the fact that adolescents with ASD had smaller volumes of gray matter in the insula than normal adolescents (Kosaka et al. 2010). Additionally, we investigated brain activity associated with emotional changes by controlling subjects’ shame-related emotion generated by their own faces, taking advantage of the fact that self-conscious emotions are strengthened by the presence of others. This experiment demonstrated that the right insula plays an important role in the neural substrates of self-conscious emotions associated with self-face recognition, because the activity of the right insular cortex was positively correlated with an increase in self-conscious emotion due to the presence of “others’ eyes” (Morita et al. 2013); however, this response was not observed in the ASD group (Morita et al. 2016). This result demonstrates that the neural activity of the right insula is a potential SBM.

(2) Preference for Conspecifics

At around 3 months after birth, human infants start to recognize biological motions. In an fMRI experiment targeted at adults, we demonstrated that this recognition is represented by areas responsible for relatively early stages of visual processing (Morito et al. 2009).

(3) Reciprocal imitation

Reciprocal imitation is a primary measure of communication for human infants. From the standpoint of developmental psychology, reciprocal imitation is related to the development of infants’ sensory perception of contingency (i.e., the temporal relationship between an anticipatory phenomenon and the following one). By around 3 months after birth, infants become to be able to recognize agency, i.e., the contingency between self-behaviors and the following physical results. Subsequently, they become to be able to perceive contingency in a social context (social contingency). Based on the hypothesis that social contingency results from functional maturation of agency and that a dysfunction of this transition is one of the causes of ASD, and because it has been reported that EBA is related to detection of the contingency between self-behavior and subsequent physical results, we made the following prediction: 1) awareness of identity between one’s own motion and another person’s motion during reciprocal imitation can induce activity of EBA; 2) the intensity of this activity correlates with the tendency of autism. We tested this hypothesis experimentally, and found that when the motions of self and others were the same, the EBA was activated on both the right and left sides. Furthermore, when subjects with strong autism tendency were imitated, the activity of the EBA on the left side was reduced. In addition, in the ASD group, the “identity effect” observed in the left EBA was smaller than that in the normal group. These results suggest that EBA represents identity between motions of self and others, and that individuals with ASD have a dysfunction in the EBA (Okamoto 2014). To investigate the function of EBA more closely, we compared the intensities of EBA activity between detection of agency and detection of social contingency. In this experiment, the subjects were tasked with moving their fingers according to spoken instructions. While the subjects were moving their fingers, they were shown a movie of either their own fingers or a stranger’s fingers, recorded prior to the experiment, as visual feedback. In the movie, the content of the motion (i.e., agreeing or disagreeing with the subject’s motion) and timing of the motion (with or without a time lag relative to the subject’s motion) were controlled. Although in every case EBA exhibited the identity effect, the activity of the left inferior frontal lobes reflected the social context. From this result, the areas that constitute human mirror neuron system are considered to formulate a functional hierarchy involved in self–other distinctions (Sasaki et al. in preparation). This result demonstrates that EBA neural activity is a potential SBM.

(4, 6) Lying and morals

A listener’s judgment regarding whether a speaker was telling a lie was represented by the neural substrates of moral judgment (canonicity) and those of intention. Additionally, the left temporo-parietal junction is related to both types of neural substrates (Harada et al. 2009).

(5) Sarcasm

We found that some of the neural substrates of theory of mind are related to those of sarcasm, which individuals with ASDs have difficulties in perceiving, and the neural substrates of sarcasm were distinct from those underlying the processing of metaphors. (Uchiyama et al. 2012). 

(7) Empathy

Empathy is thought to consist of an emotional element and a cognitive element, in which perspective plays an important role. We found that the neural substrates underlying empathy exist in the posterior cingulate gyrus and the temporo-parietal junction (Mano et al. 2009). 

(8) Prosocial behavior

An individual’s behavior, including prosocial behavior, is motivated not only by material rewards but also by social rewards, such as a good reputation in society. In decision-making in a social situation, it is necessary to compare different rewards, such as the monetary and social rewards, using a single common scale. We investigated the role of the striatum in such cases. The subjects of this experiment engaged in decision-making tasks regarding whether to make a donation, while they were either observed or not observed by others. During the tasks, the subjects underwent fMRI scans. Especially high activities in the ventral striatum on both sides were observed in cases in which subjects made donations while being watched by others (i.e., expecting a high social reward), as well as those in which they elected not to donate (and kept the money) while not being watched by others (i.e., expecting to earn a monetary reward without paying any social cost). This result shows that in the striatum, various kinds of rewards are processed as “brain currency,” and the striatum plays a key role in social decision-making (Izuma et al. 2010a). On the other hand, the activity of the medial prefrontal area was specific to social rewards. Thus, a rating given by others is represented by the medial prefrontal area, and is defined as a “social reward” by striatum. Specifically, the interaction between the reward system (including the striatum) and the neural substrates of theory of mind is related to social reward (Izuma et al. 2010b).

In addition to social rewards, empathy also plays an important role as a motivation for prosocial behavior. Previously, the motivation for helpful behavior was attributed to the individual’s desire to remove his/her own empathetic pain by helping a person in a painful situation (i.e., in which he/she feels the person’s pain as his/her own). On the other hand, it has also been pointed out that the warm glow effect, i.e., the emotional satisfaction generated by taking action to help others, can also serve as a motivation for helping behaviors. To identify the relationship between empathy and the warm glow effect, we conducted an experiment in which a pair of subjects (one male and one female) virtually tossed a ball back and forth with another pair of the same gender composition. In this experiment, we created a situation in which a certain member was operationally ostracized from the ball exchange. We chose romantic partners as subject pairs for this fMRI experiment, based on the fact that empathy depends on the degree of intimacy between two individuals. The results showed that regardless of whether the other member of a pair was a romantic partner or stranger, the number of tosses to the member who had been ostracized from the ball exchanges increased (thoughtful behavior), and the subjects’ striatum became significantly more active. The activity of the striatum during thoughtful behavior correlated with the emotional empathy scale when members of the pair were romantic partners, and with the cognitive empathy scale when they were not romantic partners. This result shows that prosocial behavior is induced by the positive emotion (warm glow effect) associated with the behavior; that the warm glow effect is represented by the activity of striatum, a part of the reward system; and that the intensity of the activity has a positive correlation with empathy (Kawamichi et al. 2012.)

(2) Development of a measurement method for eye gaze and behavior among multiple individuals and simultaneous fMRI measurement of two individuals

We formulated a quantitative measurement technique for the “bond” with others through eye contact by developing a system that simultaneously measures motions of two face-to-face individuals and applying a time-series analysis technique based on a multivariable self regression model (Okazaki et al. 2015). Additionally, we developed a simultaneous measurement technique that employs two MRI instruments to measure the neural activity underlying the interaction between two individuals, and measured neural activity during joint attention or eye contact. ‘Joint attention’ refers to a process in which two individuals share attention directed at the same object, which is initiated by eye contact. Eye contact (mutual gazing) plays an essential role in communication that links individuals and also promotes development of joint attention. Typically, human infants start sharing attention via eye gaze at age of 6–12 months. This reflects the emergence of the ability to make conjectures about others’ intentions (i.e., theory of mind), which is considered to be a precursor of language development. The absence of this kind of sharing is considered to be an early sign of autism. However, the neural substrates underlying sharing via eye gaze have not been elucidated. In particular, the neural substrates of sharing, an interaction that takes place between individuals, are indispensable for the simultaneous measurement and analysis of two individuals’ neural activities. We developed a system that uses two MRI instruments to simultaneously measure neural activity generated during the interaction between two individuals, and used this system to measure neural activity during joint attention and eye contact. The experiment proceeded as follows: subjects engaged in mutual gazing as the baseline, and exchanged gazes when they were tasked with joint attention. Using the data obtained, we calculated the correlation between the two individuals’ brain time-series data at every voxel, after all brain activity related to the joint attention task was removed using an acoustic time series. A higher correlation between the activities of the right inferior frontal gyrus of each brain was observed in paired individuals (i.e., measured simultaneously) than in non-paired individuals (i.e., not measured simultaneously). This result shows that this region is related to sharing of intention during mutual gazing (Saito and Tanabe et al. 2010). For pairs including one autistic subject and one normal subject, the synchronization between the neural activities of the right side prefrontal areas was lost, and performance in the joint attention task was reduced, not only in the autistic subjects but also in the normal subjects. Thus, synchronization between neural activities in the right side prefrontal areas of both brains is considered to play an important role in implementation of joint-attention tasks (Tanabe and Kosaka et al. 2012). In addition, we conducted simultaneous measurement of two subjects engaging only in eye contact (i.e., without any tasks) before and after they addressed the joint-attention task. By implementing the joint-attention task, the area exhibiting “resonance of brain activity” during eye contact moved to the front part of the area considered to be responsible for the mirror-neuron system, in particular to the right inferior frontal lobes. The occurrence of resonance of the right inferior frontal lobes was specific to paired subjects and to the task, as was the area activated by the joint-attention task. This result indicates that the right inferior frontal lobes has a relationship with sharing attention with others and creation of associated memories (Koike et al. 2016). This was the first finding to demonstrate the occurrence of resonance of brain activity during eye contact by simultaneous brain function measurement using two MRI instruments. This is an important step in elucidating the neural substrates underlying social interactions among multiple individuals. In addition, these results show that measurement of human behavior and quantitation of inter-individual interactions at level of neural activity are important SBMs.