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The mirror neuron system consists of fronto-parietal regions and responds to both goal-directed action execution and observation. The broader action observation network is specifically involved in observation of actions and is thought to play a role in understanding the goals of the motor act, the intention of others, empathy, and language. Many, but not all, studies have found mirror neuron system or action observation network dysfunction in autism spectrum disorder. The objective of this study was to use observation of a goal-directed action fMRI paradigm to examine the action observation network in autism spectrum disorder and to determine whether fronto-parietal activation is associated with language ability. Adolescents with autism spectrum disorder (n = 23) were compared to typically developing adolescents (n = 20), 11–17 years. Overall, there were no group differences in activation, however, the autism spectrum group with impaired expressive language (n = 13) had significantly reduced inferior frontal and inferior parietal activation during action viewing. In controls, right supramarginal gyrus activation was associated with higher expressive language; bilateral supramarginal and left pars opercularis activation was associated with better verbal-gesture integration. Results suggest that action-observation network dysfunction may characterize a subgroup of individuals with autism spectrum disorder with expressive language deficits. Therefore, interventions that target this dysfunctional network may improve expressive language in this autism spectrum subgroup. Future treatment studies should individualize therapeutic approaches based on brain-behavior relationships.

Children with chromosome 22q11.2 deletion syndrome (22q11.2DS) exhibit impaired ability to process and understand emotions in others. We measured structural connectivity in children and adolescents with 22q11.2DS (n = 28) and healthy controls (n = 29). Compared to controls, those with 22q11.2DS had poorer social skills and more difficulty recognizing facial emotions. Children with 22q11.2DS also had higher fractional anisotropic diffusion in right amygdala to fusiform gyrus white matter pathways. Right amygdala to fusiform gyrus fractional anisotropy values partially mediated the relationship between 22q11.2DS and social skills, as well as the relationship between 22q11.2DS and emotion recognition accuracy. These findings provide insight into the neural origins of social skills deficits seen in 22q11.2DS and may serve as a biomarker for risk of future psychiatric problems.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by language and communication impairments, social impairments, and repetitive behaviors or restricted interests. Previous studies of semantic functions have found differences in semantic processing and differences in the activation of the language network in adults with ASD compared to controls. The goal of this study is to examine semantic functions in adolescents with ASD compared to typically developing adolescents. We utilized fMRI with a reading version of a response-naming task to investigate activation in 12 right-handed adolescent boys with ASD and 12 typically developing boys. Both groups performed the task at ceiling levels. Boys with ASD had significantly stronger activation than controls in Broca's area, which was less left lateralized in ASD individuals. Controls had a significant correlation between frontal and temporal language area activation in the left hemisphere, whereas ASD adolescents did not. Direct group comparisons revealed additional regions activated in the ASD group relative to the control group. These results suggest differences in semantic organization, approaches to the semantic task, or efficiency in semantic processing in ASD adolescents relative to typically developing adolescents. (JINS, 2008, 14, 967–979.)

Impairments in language and communication are core features of autism spectrum disorder (ASD). The anatomy of critical language areas has been studied in ASD with inconsistent findings. We used MRI to measure gray matter volume and asymmetry of Heschl's gyrus, planum temporale, pars triangularis, and pars opercularis in 40 children and adolescents with ASD and 40 typically developing individuals, each divided into younger (7-11 years) and older (12-19 years) cohorts. The older group had larger left planum temporale volume and stronger leftward asymmetry than the younger group, regardless of diagnosis. The pars triangularis and opercularis together were larger in ASD than controls. Correlations between frontal language areas with language and symptom severity scores were significant in younger ASD children. Results suggest similar developmental changes in planum temporale anatomy in both groups, but group differences in pars triangularis and opercularis that may be related to language abilities and autism symptom severity.

Deficits in communication are a core feature of autism spectrum disorder (ASD), however, structural language abilities are highly variable, ranging from minimally verbal to superior linguistic skills. Differences in the anatomy of cortical language regions, including anterior and posterior areas, have been found in ASD. It remains unclear, however, if anatomical differences distinguish individuals with impaired expressive language from those without such deficits. In addition, anatomical differences have not been explored in children with extremely low expressive language. This study included 34 boys with ASD, 7–11 years old, including an expressive language impaired group (n = 17) and an average-high language group (n = 17). The language impaired group was subdivided into a low (n = 9) and extremely low (n = 8) language subgroup for exploratory analyses to determine whether children with ASD with extremely low expressive language abilities exhibit distinct anatomy. Gray matter volume of the pars triangularis, pars opercularis, and planum temporale (PT) were measured on MRIs. PT volume was smaller in the ASD group with expressive language impairment relative to those without language deficits. The right PT volume was also positively correlated with language scores. The exploratory analyses revealed differences in the left PT, with smaller volume in the extremely low language subgroup, relative to the average and moderately low language groups. Results suggest that smaller PT volumes in both hemispheres are associated with severe language impairments in ASD. The PT may therefore, be a biomarker of language outcome in young children with ASD, with more studies of PT anatomy necessary.

Children with autism spectrum disorder (ASD) are highly variable in their language abilities, but the neural bases of these individual differences are poorly understood. Structural magnetic resonance imaging (MRI) and magnetic resonance diffusion tensor imaging (DTI) tractography were used to examine asymmetries in language-related gray- and white-matter and their relationships to language ability in a sample of 20 children with ASD, aged 4–7 years, and a reference sample of 20 typically developing (TD) children, aged 6–11 years. Children with ASD did not differ significantly from TD children in gray matter asymmetries, but were significantly less left-lateralized than TD children in the volume and radial diffusivity (RD) of the arcuate fasciculus (AF). They did not differ in the fractional anisotropy (FA) or the mean or axial diffusivity of the AF. Within the ASD group, exploratory analyses revealed that decreased leftward/increased rightward asymmetry of pars opercularis was associated with higher language ability and bilaterally increased FA and decreased RD of the AF. In conclusion, children with ASD exhibited atypical asymmetry in language-related white-matter structure as well as an atypical pattern of brain-language relationships that suggest that they may meet language milestones and acquire normal language via a different neurodevelopmental trajectory from TD children.

The left hemisphere plays a predominant role in speech-language functions. Anatomical asymmetries of perisylvian speech-language regions have been found with evidence that leftward asymmetries are associated with language dominance. There is also evidence that sex-linked differences in the functional organization of language exist, although sex-linked anatomical differences have not been extensively studied and results have been conflicting. For example, developmental language disorders are male predominate, and women may have more bilaterally represented language functions. Given the controversy in the literature and the need to learn more about sex-linked anatomical differences in healthy adults, a series of experiments were designed to study the anatomy and function of perisylvian language related cortex. Volumetric MRI was used to measure gray matter volumes of posterior language areas, including Heschl's gyrus (HG), planum temporale (PT), and posterior superior temporal gyrus (pSTG) in 48 right-handed men and women, matched for age and education and frontal regions, including the pars triangularis (PTR), pars opercularis (POP), and diagonal sulcus (DS) in 60 right-handed men and women, matched for age and education. Language tests were administered to a subsample of subjects. There were no consistent HG asymmetries and no sex differences. There was a leftward PT asymmetry (L > R), but no sex differences. For the pSTG, men had rightward asymmetry (R > L), while women were as likely to have R > L as L > R. For the temporal areas together, in men about equal numbers had L > R as R > L, whereas women had L > R. There were no asymmetries or sex differences for any frontal language areas. When a measure of listening comprehension was examined, there was a trend for a significant PT asymmetry direction-by-sex interaction. Women with rightward PT asymmetry performed better, whereas men with leftward PT scored better. These results are interesting because the PT mediates auditory processing and atypical (R > L) PT anatomy has been found in individuals with dyslexia. Although speculative, it may be that atypical PT anatomy in women is not associated with aberrant function, whereas in men atypical anatomy may be a neural risk for dysfunctional language development. Future studies should explore these important relationships in neurodevelopmental and acquired language disorders.