The present study explored the association between social function and EF in children with ASD and found that the social deficit was positively associated with the executive dysfunction. We further identified the shared underlying brain FC link between right amygdala and right inferior frontal gyrus might mediate the effect of EF on social function. These findings provided a new insight for understanding the neuro mechanisms of the co-occurrence of social deficit and executive dysfunction in ASD patients, and further inform the intervention target.
The present results confirmed that social deficits and executive dysfunction were positively related to each other in children with ASD, and social deficits in ASD children were predominately accompanied by executive dysfunction. These results were similar to previous findings, which indicated that components of EF might contribute to social communication in ASD patients(6, 14, 45, 46). The two major components of EF were positively related to the social awareness, social cognition, and social communication in the present study. The association between organization of material in EF and social cognition, communication, motivation, autistic mannerisms, emotional control in EF and social awareness in social deficit, inhibition in EF and social motivation in social function were not statistically significant. As described in a previous study, the organization of materials domain was not significantly different between children with ASD and typically developing children (47). As a result, abnormalities in the organization of materials might not be a predictor of ASD or social function in children with ASD. Studies that evaluated inhibitory control in ASD children reported mixed results. A review reported that inhibitory control ability in ASD would predict future scholastic, occupational, and social interaction performance(10). Further studies are needed to clarify the association between inhibition and autistic mannerisms. The shift domain reflects the ability to change from one situation to another, and it was closely related to higher-order restricted and repetitive behaviors and interests(48). In the present study, we did not find a statistically significant correlation between shift and autistic mannerisms.
The present results indicated that brain regions that are related to social deficits in children with ASD were mostly located in the supramarginal gyrus, which is also involved in visual experiences(49). The supramarginal gyrus and angular gyrus are two components of the inferior parietal cortex, which is an important hub in the default mode network (50). Alterations of activation of the supramarginal gyrus, inferior partial cortex, and default mode network were commonly reported in children with ASD (51, 52). Alterations of FC between the supramarginal gyrus and caudate were previously reported to be involved in other cognition processes, including hyperarousal symptoms in insomnia patients and secondary language vocabulary acquisition(53, 54). In our study, it might also be related to social function in ASD children. Moreover, the supramarginal gyrus might be implicated in failure of the emotional self-other distinction in children with ASD(55). Numerous imaging studies suggested that FC abnormalities in the supramarginal gyrus are related to emotional processes, such as interoception, empathy, and attentional processing(55–57). Social-emotional dysfunctions are core symptoms in patients with ASD. Interventions or training that target emotional recognition and understanding might in turn impact social interaction in ASD patients(20, 58). Other brain regions in the present study that were related to social function in ASD children included the frontal lobe and limbic lobe. Previous studies reported that the inferior frontal gyrus was abnormally activated in ASD children during emotional-social expression(59, 60). Atypical FC in the limbic lobe and cingulate was also observed in ASD patients(61). The cingulate is an important component of the limbic lobe. It is a white matter joint of the frontal lobe, parietal lobe, and temporal lobe, and this brain region is related to EF, emotion, and pain(62). The hippocampus is another brain region in the limbic lobe that is related to memory and relational recoding(63). Changes in FC between the limbic lobe and amygdala and between the limbic lobe and putamen in the present study were consistent with a previous study that showed that social deficits in ASD patients might be related to atypical amygdala-cingulate connectivity(64).
Executive dysfunction is a common symptom in ASD patients. Brain regions that are associated with impairments in EF were predominantly located in the frontal lobe, including the superior part, inferior part, and middle part. Several studies provided evidence that the frontal lobe is a key brain region for EF. Damage to the frontal lobe might contribute to executive dysfunction in many disorders(65–68). The frontal lobe is involved various cognitive and emotional processes. Developmental changes in frontal lobe function occur during aging, which can impact executive control, decision-making, working memory, and inhibition(69). Individuals with ASD might exhibit the prolonged heterogeneity of frontal lobe dysfunction(70). In the present study, abnormal FC links were found between the frontal lobe and amygdala, caudate, and putamen in ASD children. Consistent with a previous study, alterations of frontal-striatal connectivity contribute to deficits in facial viewing, which is another core characteristic of children with ASD(71). The left gyrus rectus is a part of the inferior frontal gyrus (IFG) and involved in social interaction(72). This region was significantly associated with EF in children with ASD in the present study and previous studies(72, 73). Correlations were found between the right amygdala and left superior occipital gyrus and between the left caudate and supramarginal gyrus in ASD children who presented executive dysfunction, which was previously reported in autistic subjects(74, 75). According to Simard et al., the occipital gyrus is related to visual and cognitive processing, such as the identification of correct answers in a reasoning task(74).
Functional connectivity links that significantly mediated the association between social deficits and executive dysfunction included the right amygdala and right inferior frontal gyrus. The amygdala and inferior frontal gyrus were reported to play a role in social and emotional processes(76, 77). Atypical frontal lobe development and function have been described in many psychological disorders. The frontal lobe is involved in many cognitive progresses, including emotion, personality, self-awareness, social function, and attention(78). Abnormal frontal lobe-amygdala connectivity has been previously reported in ASD patients, which could contribute to social deficits(79). The atypical activation of these brain regions would prevent appropriate reactions to social or emotional stimuli (76). The results of a previous neuroimaging meta-analysis suggested that subjects with ASD exhibited aberrant activation in the bilateral inferior frontal gyrus and bilateral amygdala during face processing(80). Executive function was associated with the amygdala, the dorsolateral prefrontal cortex, and connectivity between core regions, including the amygdala and thalamus(81). Accumulating evidence suggests changes in activation of the amygdala and inferior frontal gyrus in ASD subjects and associations between FC and clinical characteristics. The present study found that alterations of FC between these two regions mediated the correlation between two characteristics of ASD—social deficits and executive dysfunction—which might reveal a neural mechanism of the pathogenesis of ASD. Furthermore, our findings focused on the behavioral associated amygdala-circuits, which might expand the treatment routes for ASD subjects.
The present study has several limitations. First, all participants were ASD subjects. The co-occurrence of social deficits and executive dysfunction can also be observed in the general population of children. Unknown is whether the mediation effect we found is also appliable to typically developing children with social deficits and executive dysfunction. Second, we used various evaluations of social function and EF in children with ASD. We chose the SRS and BRIEF because correlations between SRS and BRIEF scores have been widely described in the literature. Further studies that evaluate these associations using other measurements are needed. Third, the majority of the participants were boys. The prevalence of autism is 4–5 times higher in males than in females.
In conclusion, we found a significant association between social deficits and executive dysfunction in ASD children. We also explored the mediation effect of FC links and found that alterations of FC between the amygdala and inferior frontal gyrus significantly mediated the correlation between clinical symptoms, which may further illustrate the underlying mechanism of ASD.