Language and communication deficits are among the core features of autism spectrum disorder (ASD). Reduced or reversed asymmetry of language has been found in a number of disorders, including ASD. Studies of healthy adults have found an association between language laterality and anatomical measures but this has not been systematically investigated in ASD. The goal of this study was to examine differences in gray matter volume of perisylvian language regions, connections between language regions, and language abilities in individuals with typical left lateralized language compared to those with atypical (bilateral or right) asymmetry of language functions. 14 adolescent boys with ASD and 20 typically developing adolescent boys participated, including equal numbers of left-and right-handed individuals in each group. Participants with typical left lateralized language activation had smaller frontal language region volume and higher fractional anisotropy of the arcuate fasciculus compared to the group with atypical language laterality, across both ASD and control participants. The group with typical language asymmetry included the most right-handed controls and fewest left-handers with ASD. Atypical language laterality was more prevalent in the ASD than control group. These findings support an association between laterality of language function and language region anatomy. They also suggest anatomical differences may be more associated with variation in language laterality than specifically with ASD. Language laterality therefore may provide a novel way of subdividing samples, resulting in more homogenous groups for research into genetic and neurocognitive foundations of developmental disorders.

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 f MRI 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.)

Human primary auditory cortex (PAC) is functionally organized in a tonotopic manner. Past studies have used neuroimaging to characterize tonotopic organization in PAC and found similar organization as that described in mammals. In contrast to what is known about PAC in primates and nonprimates, in humans, the structural connectivity within PAC has not been defined. In this study, stroboscopic event-related functional magnetic resonance imaging (fMRI) was utilized to reveal mirror symmetric tonotopic organization consisting of a high-low-high frequency gradient in PAC. Furthermore, diffusion tensor tractography and probabilistic mapping was used to study projection patterns within tonotopic areas. Based on earlier physiological and histological work in nonhuman PAC, we hypothesized the existence of cross-field isofrequency (homotopic) and within-field non-isofrequency (heterotopic)-specific axonal projections in human PAC. The presence of both projections types was found in all subjects. Specifically, the number of diffusion tensor imaging (DTI) reconstructed fibers projecting between high- and low-frequency regions was greater than those fibers projecting between 2 high-frequency areas, the latter of which are located in distinct auditory fields. The fMRI and DTI results indicate that functional and structural properties within early stages of the auditory processing stream are preserved across multiple mammalian species at distinct evolutionary levels.

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.

Language processing involves multiple neuronal structures in the human auditory cortex. Although a variety of neuroimaging and mapping techniques have been implemented to better understand language processing at the level of the auditory cortex, much is unknown regarding how and by what pathways these structures interact during essential tasks such as sentence comprehension. In this study, the effective and structural connectivity at the level of the auditory cortex were investigated. First, blood oxygenation leveldependent (BOLD) responses were measured with time-resolved functional magnetic resonance imaging (fMRI) during audition of short sentences. Once BOLD activation maps were obtained, the effective connectivity between primary auditory cortex and the surrounding auditory regions on the supratemporal plane and superior temporal gyrus (STG) were investigated using Granger causality mapping (GCM). Effective connectivity was observed between the primary auditory cortex and (1) the lateral planum polare and anterior STG, and (2) the lateral planum temporale and posterior STG. By using diffusion tensor probabilistic mapping (DTPM), rostral and caudal fiber pathways were detected between regions depicting effective connectivity. The effective and structural connectivity results of the present study provide further insight as to how auditory stimuli (i.e., human language) is processed at the level of the auditory cortex. Furthermore, combining BOLD fMRI-based GCM and DTPM analysis could provide a novel means to study effective and structural connectivity not only in the auditory cortex, but also in other cortical regions.

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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.

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