Measurements of the lateral cerebellar hemispheres using near-infrared spectroscopy through comparison between autism spectrum disorder and typical development.

The cerebellum plays a vital role in cognition, communication with the cerebral cortex, and fine motor coordination. Near-infrared spectroscopy (NIRS) is a portable, less restrictive, and noninvasive functional brain imaging method that can capture brain activity during movements by measuring the relative oxyhemoglobin (oxy-Hb) concentrations in the blood. However, the feasibility of using NIRS to measure cerebellar activity requires discussion. We compared NIRS responses between areas assumed to be the cerebellum and the occipital lobe during a fine motor task (tying a bow knot) and a visual task. Our results showed that the oxy-Hb concentration increased more in the occipital lobe than in the cerebellum during the visual task (p =.034). In contrast, during the fine motor task, the oxy-Hb concentration decreased in the occipital lobe but increased significantly in the cerebellum, indicating a notable difference (p =.015). These findings suggest that we successfully captured cerebellar activity associated with processing, particularly fine motor coordination. Moreover, the observed responses did not differ between individuals with autism spectrum disorder and those with typical development. Our study demonstrates the meaningful utility of NIRS as a method for measuring cerebellar activity during movements.

Atypical cortical activation during fine motor tasks in autism spectrum disorder.

Individuals with autism spectrum disorder (ASD) often have difficulty with coordinated fine motor skills, but the degree of difficulty significantly varies from person to person. To elucidate the cause of this diversity, we monitored brain activity during fine movement tasks (tying bowknots) by near-infrared spectroscopy in 17 adults with ASD and 18 adults with typical development matched for age, gender, and intelligence quotient (IQ). We also examined the relationship between brain activation and developmental characteristics, including ASD severity, using the Autism-Spectrum Quotient and the Multi-dimensional Scale for Pervasive Developmental Disorder and Attention-Deficit/Hyperactivity Disorder. Although participants in the ASD group did not show significant clumsiness, their right prefrontal cortexes were relatively less activated, particularly in individuals with poor social skills and inattention. Our study indicates that individuals with ASD traits may use different strategies when performing fine movements; that is, they less use the brain areas responsible for processing visual image or planning behaviors.

Cultural influences on neural systems of intergroup emotion perception: An fMRI study.

Cultural factors, such as cultural group membership, have been shown to affect neural bases of face and emotion perception. However, little is known about how cultural factors influence neural processing of emotional faces expressed by in-group and out-group members. In this study, we examined cultural influences on neural activation during the intergroup perception of negative emotional faces. We used functional magnetic resonance imaging to compare neural activation during intergroup emotion processing across cultures in three participants groups; two monocultural groups (i.e. Caucasian-Americans and native Japanese) and a bicultural group (i.e. Japanese-Americans). During scanning, the participants completed an emotional match-to-sample task consisting of negative facial expressions of Japanese and Caucasians. Our results show cultural modulation of neural response in the bilateral amygdala as a function of in-group biases and collectivistic values. Additionally, bicultural Japanese-Americans showed enhanced neural responses in the ventral medial prefrontal and posterior cingulate cortices, which had been related to self-related processing, during the perception of negative facial expression of Japanese. Neural activation in the ventral and posterior cingulate cortices reflected individuals' collectivistic tendencies only in the Japanese-American group, possibly due to greater sensitivity to ingroup biases in bicultural individuals. Our results demonstrate the influence of culture on neural responses during the perception of intergroup emotion from faces.

Do Individuals With Autism Spectrum Disorders Help Other People With Autism Spectrum Disorders? An Investigation of Empathy and Helping Motivation in Adults With Autism Spectrum Disorder.

Individuals with autism spectrum disorder (ASD) often lack cognitive empathy, so they experience difficulty in empathizing with others. Although deficits in social abilities, such as empathy, have been demonstrated in previous studies, most stimuli used in previous studies were developed for typically developing (TD) individuals. Previous studies have demonstrated that adults with and without ASD display empathetic responses toward similar others. Adults with ASD (n = 22, 7 women and 15 men, mean age = 26.8 years) and intelligence- and age-matched TD adults (n = 20, 8 women and 12 men, mean age = 24.0 years) participated in the study. They were instructed to read 24 stories (12 stories featured protagonists with characteristics of ASD, and the other 12 featured TD protagonists) and respond to the following questions: "How did the protagonist feel?" and "Would you help if the protagonist were in trouble?" After controlling for alexithymia and AQ based on multiple regression analyses, individuals with ASD empathize with other people who have ASD and are motivated to help other people with ASD. Additionally, social skills and attention to detail were associated with decreased helping motivation for story characters with ASD. Social skills among AQ subscales (social skills, attention switching, attention to detail, communication, and imagination) were the most potent predictor of decreased helping motivation. These findings suggest that the reason why individuals with ASD are considered to have limited cognitive empathy and helping motivation could be related to alexithymia and the lack of social skills and attention to detail, which are related to atypical perception.

Thalamocortical Hyperconnectivity and Amygdala-Cortical Hypoconnectivity in Male Patients With Autism Spectrum Disorder.

Background: Analyses of resting-state functional magnetic resonance imaging (rs-fMRI) have been performed to investigate pathophysiological changes in the brains of patients with autism spectrum disorder (ASD) relative to typically developing controls (CTLs). However, the results of these previous studies, which have reported mixed patterns of hypo- and hyperconnectivity, are controversial, likely due to the small sample sizes and limited age range of included participants. Methods: To overcome this issue, we analyzed multisite neuroimaging data from a large sample (n = 626) of male participants aged between 5 and 29 years (mean age = 13 years). The rs-fMRI data were preprocessed using SPM12 and DPARSF software, and signal changes in 90 brain regions were extracted. Multiple linear regression was used to exclude the effect of site differences in connectivity data. Subcortical-cortical connectivity was computed using connectivities in the hippocampus, amygdala, caudate nucleus, putamen, pallidum, and thalamus. Eighty-eight connectivities in each structure were compared between patients with ASD and CTLs using multiple linear regression with group, age, and age × group interactions, head movement parameters, and overall connectivity as variables. Results: After correcting for multiple comparisons, patients in the ASD group exhibited significant increases in connectivity between the thalamus and 19 cortical regions distributed throughout the fronto-parietal lobes, including the temporo-parietal junction and posterior cingulate cortices. In addition, there were significant decreases in connectivity between the amygdala and six cortical regions. The mean effect size of hyperconnectivity (0.25) was greater than that for hypoconnectivity (0.08). No other subcortical structures showed significant group differences. A group-by-age interaction was observed for connectivity between the thalamus and motor-somatosensory areas. Conclusions: These results demonstrate that pathophysiological changes associated with ASD are more likely related to thalamocortical hyperconnectivity than to amygdala-cortical hypoconnectivity. Future studies should examine full sets of clinical and behavioral symptoms in combination with functional connectivity to explore possible biomarkers for ASD.

Decision-Making Based on Social Conventional Rules by Elderly People.

Information used by older adults engaging in a social decision making task of judging a protagonist as a good or a bad person was investigated. Older (n = 100, 50 women, mean age = 63.6 years) and younger (n = 100, 50 women, mean age = 25.7 years) adults participated in a web-based survey. In Experiment 1, we assessed participants' rapid decision-making processes when making good or bad judgments after reading consecutive sentences without reviewing previously read sentences. The percentages of good judgments were analyzed. In Experiment 2, two protagonists engaging in a deliberate decision-making process were presented, and participants were asked to judge better and worse protagonists. The percentages of behavior-based judgments were analyzed. Results of Experiment 1 indicated that older adults judged protagonists as "good" more often than younger adults. Especially, older adults judged protagonists with good behavior as being "good." In Experiment 2, older adults made behavior-based judgments more than younger people. Additionally, older and younger adults used information on personalities of protagonists for making judgments in situations with bad outcomes, or incongruent. Moreover, multiple regression analysis suggested that people with more general trust engaged more, whereas people with more caution engaged less in making behavior-based judgments.

Decision making processes based on social conventional rules in early adolescents with and without autism spectrum disorders.

Autism spectrum disorder (ASD) is characterized by problems with reciprocal social interaction, repetitive behaviours/narrow interests, and impairments in the social cognition and emotional processing necessary for intention-based moral judgements. The aim of this study was to examine the information used by early adolescents with and without ASD when they judge story protagonists as good or bad. We predicted that adolescents with ASD would use protagonists' behaviour, while typically developing (TD) adolescents would use protagonists' characteristics when making the judgements. In Experiment 1, we measured sentence by sentence reading times and percentages for good or bad judgements. In Experiment 2, two story protagonists were presented and the participants determined which protagonist was better or worse. Experiment 1 results showed that the adolescents with ASD used protagonist behaviours and outcomes, whereas the TD adolescents used protagonist characteristics, behaviours, and outcomes. In Experiment 2, TD adolescents used characteristics information when making "bad" judgements. Taken together, in situations in which participants cannot go back and assess (Experiment 1), and in comparable situations in which all information is available (Experiment 2), adolescents with ASD do not rely on information about individual characteristics when making moral judgements.

Cultural influences on neural basis of inhibitory control.

Research on neural basis of inhibitory control has been extensively conducted in various parts of the world. It is often implicitly assumed that neural basis of inhibitory control is universally similar across cultures. Here, we investigated the extent to which culture modulated inhibitory-control brain activity at both cultural-group and cultural-value levels of analysis. During fMRI scanning, participants from different cultural groups (including Caucasian-Americans and Japanese-Americans living in the United States and native Japanese living in Japan) performed a Go/No-Go task. They also completed behavioral surveys assessing cultural values of behavioral consistency, or the extent to which one's behaviors in daily life are consistent across situations. Across participants, the Go/No-Go task elicited stronger neural activity in several inhibitory-control areas, such as the inferior frontal gyrus (IFG) and anterior cingulate cortex (ACC). Importantly, at the cultural-group level, we found variation in left IFG (L-IFG) activity that was explained by a cultural region where participants lived in (as opposed to race). Specifically, L-IFG activity was stronger for native Japanese compared to Caucasian- and Japanese-Americans, while there was no systematic difference in L-IFG activity between Japanese- and Caucasian-Americans. At the cultural-value level, we found that participants who valued being "themselves" across situations (i.e., having high endorsement of behavioral consistency) elicited stronger rostral ACC activity during the Go/No-Go task. Altogether, our findings provide novel insight into how culture modulates the neural basis of inhibitory control.

Similarity hypothesis: understanding of others with autism spectrum disorders by individuals with autism spectrum disorders.

Individuals with an autism spectrum disorder (ASD) are generally thought to lack empathy. However, according to recent empirical and self-advocacy studies, individuals with ASD identify with others with ASD. Based on mutual understanding, individuals with ASD respond empathically to others with these disorders. Results have shown that typically developing (TD) adults identify with TD fictional characters, and that such identification plays a critical role in social cognition. TD individuals retrieve episodes involving TD individuals faster than they retrieve episodes involving ASD individuals. Individuals with ASD also show a "similarity effect" whereby they retrieve stories involving ASD individuals more effectively when the stories have consistent outcomes than when they have inconsistent outcomes. In this context, I hypothesized that similarities between a perceiver and a target facilitate cognitive processing. This hypothesis was named the "similarity hypothesis". Perceivers empathize with targets similar to themselves, which facilitates subsequent cognitive processing. Behavioral and neuroimaging studies are reviewed based on the similarity hypothesis.

Autistic empathy toward autistic others.

Individuals with autism spectrum disorder (ASD) are thought to lack self-awareness and to experience difficulty empathizing with others. Although these deficits have been demonstrated in previous studies, most of the target stimuli were constructed for typically developing (TD) individuals. We employed judgment tasks capable of indexing self-relevant processing in individuals with and without ASD. Fourteen Japanese men and 1 Japanese women with high-functioning ASD (17-41 years of age) and 13 Japanese men and 2 TD Japanese women (22-40 years of age), all of whom were matched for age and full and verbal intelligence quotient scores with the ASD participants, were enrolled in this study. The results demonstrated that the ventromedial prefrontal cortex was significantly activated in individuals with ASD in response to autistic characters and in TD individuals in response to non-autistic characters. Although the frontal-posterior network between the ventromedial prefrontal cortex and superior temporal gyrus participated in the processing of non-autistic characters in TD individuals, an alternative network was involved when individuals with ASD processed autistic characters. This suggests an atypical form of empathy in individuals with ASD toward others with ASD.

Episodic memory retrieval for story characters in high-functioning autism.

BACKGROUND: The objective of this study was to examine differences in episodic memory retrieval between individuals with autism spectrum disorder (ASD) and typically developing (TD) individuals. Previous studies have shown that personality similarities between readers and characters facilitated reading comprehension. Highly extraverted participants read stories featuring extraverted protagonists more easily and judged the outcomes of such stories more rapidly than did less extraverted participants. Similarly, highly neurotic participants judged the outcomes of stories with neurotic protagonists more rapidly than did participants with low levels of neuroticism. However, the impact of the similarity effect on memory retrieval remains unclear. This study tested our 'similarity hypothesis', namely that memory retrieval is enhanced when readers with ASD and TD readers read stories featuring protagonists with ASD and with characteristics associated with TD individuals, respectively. METHODS: Eighteen Japanese individuals (one female) with high-functioning ASD (aged 17 to 40 years) and 17 age- and intelligence quotient (IQ)-matched Japanese (one female) TD participants (aged 22 to 40 years) read 24 stories; 12 stories featured protagonists with ASD characteristics, and the other 12 featured TD protagonists. Participants read a single sentence at a time and pressed a spacebar to advance to the next sentence. After reading all 24 stories, they were asked to complete a recognition task about the target sentence in each story. RESULTS: To investigate episodic memory in ASD, we analyzed encoding based on the reading times for and readability of the stories and retrieval processes based on the accuracy of and response times for sentence recognition. Although the results showed no differences between ASD and TD groups in encoding processes, they did reveal inter-group differences in memory retrieval. Although individuals with ASD demonstrated the same level of accuracy as did TD individuals, their patterns of memory retrieval differed with respect to response times. CONCLUSIONS: Individuals with ASD more effectively retrieved ASD-congruent than ASD-incongruent sentences, and TD individuals retrieved stories with TD more effectively than stories with ASD protagonists. Thus, similarity between reader and story character had different effects on memory retrieval in the ASD and TD groups.

Beyond disposition: the processing consequences of explicit and implicit invocations of empathy.

People often report empathizing with the trials and tribulations of others. While some accounts characterize empathy as a general tendency that individuals possess to differing degrees, an alternative, understudied view is that empathy emerges out of similarity-driven matches between potential targets and empathizers. The current project examines whether these matches, even when not explicitly identified, influence experiences of empathy, and whether that empathy has consequences for comprehension experiences. In two experiments, participants read stories describing protagonists as highly extraverted, highly neurotic, or neither; participants' personalities were also measured along these dimensions. Personality scores predicted participants' self-reported empathy for story protagonists, over and above measures of general empathy. Similarity between readers and protagonists also enhanced more subtle evaluations of the events befalling empathic targets. The effects of empathy have important implications for mental simulation, the motivated pursuit of knowledge, and persuasion.

Hard to "tune in": neural mechanisms of live face-to-face interaction with high-functioning autistic spectrum disorder.

Persons with autism spectrum disorders (ASD) are known to have difficulty in eye contact (EC). This may make it difficult for their partners during face to face communication with them. To elucidate the neural substrates of live inter-subject interaction of ASD patients and normal subjects, we conducted hyper-scanning functional MRI with 21 subjects with autistic spectrum disorder (ASD) paired with typically-developed (normal) subjects, and with 19 pairs of normal subjects as a control. Baseline EC was maintained while subjects performed real-time joint-attention task. The task-related effects were modeled out, and inter-individual correlation analysis was performed on the residual time-course data. ASD-Normal pairs were less accurate at detecting gaze direction than Normal-Normal pairs. Performance was impaired both in ASD subjects and in their normal partners. The left occipital pole (OP) activation by gaze processing was reduced in ASD subjects, suggesting that deterioration of eye-cue detection in ASD is related to impairment of early visual processing of gaze. On the other hand, their normal partners showed greater activity in the bilateral occipital cortex and the right prefrontal area, indicating a compensatory workload. Inter-brain coherence in the right IFG that was observed in the Normal-Normal pairs (Saito et al., 2010) during EC diminished in ASD-Normal pairs. Intra-brain functional connectivity between the right IFG and right superior temporal sulcus (STS) in normal subjects paired with ASD subjects was reduced compared with in Normal-Normal pairs. This functional connectivity was positively correlated with performance of the normal partners on the eye-cue detection. Considering the integrative role of the right STS in gaze processing, inter-subject synchronization during EC may be a prerequisite for eye cue detection by the normal partner.

"Stay tuned": inter-individual neural synchronization during mutual gaze and joint attention.

Eye contact provides a communicative link between humans, prompting joint attention. As spontaneous brain activity might have an important role in the coordination of neuronal processing within the brain, their inter-subject synchronization might occur during eye contact. To test this, we conducted simultaneous functional MRI in pairs of adults. Eye contact was maintained at baseline while the subjects engaged in real-time gaze exchange in a joint attention task. Averted gaze activated the bilateral occipital pole extending to the right posterior superior temporal sulcus, the dorso-medial prefrontal cortex, and the bilateral inferior frontal gyrus. Following a partner's gaze toward an object activated the left intraparietal sulcus. After all the task-related effects were modeled out, inter-individual correlation analysis of residual time-courses was performed. Paired subjects showed more prominent correlations than non-paired subjects in the right inferior frontal gyrus, suggesting that this region is involved in sharing intention during eye contact that provides the context for joint attention.

Transient neural activation in human amygdala involved in aversive conditioning of face and voice.

Elucidating the neural mechanisms involved in aversive conditioning helps find effective treatments for psychiatric disorders such as anxiety disorder and phobia. Previous studies using fMRI and human subjects have reported that the amygdala plays a role in this phenomenon. However, the noxious stimuli that were used as unconditioned stimuli in previous studies (e.g., electric shock) might have been ecologically invalid because we seldom encounter such stimuli in daily life. Therefore, we investigated whether a face stimulus could be conditioned by using a voice that had negative emotional valence and was collected from a real-life environment. A skin conductance response showed that healthy subjects were conditioned by using these stimuli. In an fMRI study, there was greater amygdala activation in response to the faces that had been paired with the voice than to those that had not. The right amygdala showed transient activity in the early stage of acquisition. A psychophysiological interaction analysis indicated that the subcortical pathway from the medial geniculate body to the amygdala played a role in conditioning. Modulation of the subcortical pathway by voice stimuli preceded the transient activity in the amygdala. The finding that an ecologically valid stimulus elicited the conditioning and amygdala response suggests that our brain is automatically processing unpleasant stimuli in daily life.

Dynamic cultural influences on neural representations of the self.

People living in multicultural environments often encounter situations which require them to acquire different cultural schemas and to switch between these cultural schemas depending on their immediate sociocultural context. Prior behavioral studies show that priming cultural schemas reliably impacts mental processes and behavior underlying self-concept. However, less well understood is whether or not cultural priming affects neurobiological mechanisms underlying the self. Here we examined whether priming cultural values of individualism and collectivism in bicultural individuals affects neural activity in cortical midline structures underlying self-relevant processes using functional magnetic resonance imaging. Biculturals primed with individualistic values showed increased activation within medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC) during general relative to contextual self-judgments, whereas biculturals primed with collectivistic values showed increased response within MPFC and PCC during contextual relative to general self-judgments. Moreover, degree of cultural priming was positively correlated with degree of MPFC and PCC activity during culturally congruent self-judgments. These findings illustrate the dynamic influence of culture on neural representations underlying the self and, more broadly, suggest a neurobiological basis by which people acculturate to novel environments.

Neural basis of individualistic and collectivistic views of self.

Individualism and collectivism refer to cultural values that influence how people construe themselves and their relation to the world. Individualists perceive themselves as stable entities, autonomous from other people and their environment, while collectivists view themselves as dynamic entities, continually defined by their social context and relationships. Despite rich understanding of how individualism and collectivism influence social cognition at a behavioral level, little is known about how these cultural values modulate neural representations underlying social cognition. Using cross-cultural functional magnetic resonance imaging (fMRI), we examined whether the cultural values of individualism and collectivism modulate neural activity within medial prefrontal cortex (MPFC) during processing of general and contextual self judgments. Here, we show that neural activity within the anterior rostral portion of the MPFC during processing of general and contextual self judgments positively predicts how individualistic or collectivistic a person is across cultures. These results reveal two kinds of neural representations of self (eg, a general self and a contextual self) within MPFC and demonstrate how cultural values of individualism and collectivism shape these neural representations.

The effect of a protagonist's emotional shift on situation model construction.

We examined whether readers monitored protagonists' emotional shifts and whether reader engagement influenced situation model construction. Participants read narratives that included an emotional shift in the middle of the story. In Experiment 1, participants were instructed to read stories appreciatively and to empathize with the protagonists. In Experiment 2, readers were instructed to read the stories normally, as if they were reading novels. The results from the two experiments suggest that readers monitor temporal and causal shifts as well as protagonists' emotional shifts in stories. Moreover, in Experiment 1 readers detected temporal and causal shifts regardless of th e degree oftheir engagement during the empathetic reading, while in Experiment 2 the high ego involvement group detected causal shifts during the normal reading. Thus, these results show both that readers monitor protagonists' emotional states and that reader emotional engagement c an influence situationmodel construction with normal reading.

[Effects of repetition and dual-task on output monitoring errors].

We investigated output-monitoring errors in a modified source-monitoring paradigm. Unlike the traditional paradigm that involves two phases, learning and monitoring, the modified paradigm involves three phases, learning, enactment, and monitoring. Three experiments produced two major findings. First, compared with the traditional paradigm, the modified paradigm produced fewer monitoring errors. Second, performing a dual-task during the enactment phase increased monitoring errors for the items that participants repeatedly enacted during the learning phase. In contrast, performing a dual-task during the learning phase did not influence monitoring errors. It only decreased the number of items that were enacted during the enactment phase. We concluded that monitoring errors are more likely to occur (a) when the modality of items matches between the learning and enactment phases (i.e., items are enacted during both phases), and (b) when a dual-task increases processing demands during the enactment phase.

[Roles of reader's feelings in understanding narratives: forefeel, empathy, and a sense of strangeness].

This study examined the cross-domain, anticipatory, and self-referential roles of affect (Miall, 1989) in reading short mystery novels. In Experiment 1, undergraduate students either read an entire story once or read the same story twice. During the first reading, these participants read only the first part of the story, and during the second reading, they read the entire story. They rated the importance of each sentence. Then they either described a prediction or their impression of the story. Finally, they created a title. In Experiment 2, the first group rated the importance of each sentence. The second group rated the feelings of understanding: forefeel, empathy, and a sense of strangeness. The results of both experiments showed that the relative importance of sentences shifted between first reading and second reading. As they read the end of the story, empathy increased but a sense of strangeness decreased. The results of description showed that the readers updated their interpretations in order to understand the story correctly.