Action viewing and language in adolescents with autism spectrum disorder.

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.

Structural Connectivity and Emotion Recognition Impairment in Children and Adolescents with Chromosome 22q11.2 Deletion Syndrome.

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.

Atypical PT anatomy in children with autism spectrum disorder with expressive language deficits.

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.

Atypical activation of action-semantic network in adolescents with autism spectrum disorder.

In typical adults, fMRI studies have shown activation of primary and pre-motor regions during action word processing. Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication impairments. ASD studies have shown atypical semantic processing and motor deficits. The objective of this study was to examine semantic processing of verbs in ASD. 15 ASD adolescents and 19 typically developing adolescents, 11-16years, completed a semantic similarity judgment task during fMRI. There were no differences in task accuracy or reaction time. At the group level, both groups had activation in left language areas; controls, but not ASD, also had activation in the left pre-supplementary motor area (pre-SMA). In ASD, less left frontal activation and reduced left lateralization of activation within these regions was associated with shorter reaction times and better language skills. More left temporal activation was associated with better language abilities in ASD. Differences in pre-SMA activation may relate to motor planning deficits or differences in approach to the semantic task in ASD. Results suggest that left frontal language areas may be less efficient in ASD and those who can compensate by recruiting more right hemisphere homologues may result in better language abilities.

Handedness in Children With Autism Spectrum Disorder.

The left hemisphere is usually predominant in manual skills and language, suggesting a link between hand dominance and language. Studies of autism spectrum disorder show atypical handedness; however, few have examined language-handedness associations. Handedness, assessed by task performance, and standardized receptive and expressive language tests were completed in 110 autism spectrum disorder children (96 boys; M age = 8.3 years, SD = 3.8) and 45 typically developing children (37 boys; M age = 8.6 years, SD = 4.3), 3 to 17 years of age. The autism spectrum disorder group had a lower handedness score (was less strongly lateralized) than the control group. In the autism spectrum disorder group, there was a small effect of handedness on language; right-handers had better language than non-right-handers. Results suggest poorer language prognosis may be associated with left- or mixed-handedness in autism spectrum disorder.

Structural asymmetries of language-related gray and white matter and their relationship to language function in young children with ASD.

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.

Sylvian fissure and parietal anatomy in children with autism spectrum disorder.

Autism spectrum disorder (ASD) is characterized by deficits in social functioning and language and communication, with restricted interests or stereotyped behaviors. Anatomical differences have been found in the parietal cortex in children with ASD, but parietal subregions and associations between Sylvian fissure (SF) and parietal anatomy have not been explored. In this study, SF length and anterior and posterior parietal volumes were measured on MRI in 30 right-handed boys with ASD and 30 right-handed typically developing boys (7-14 years), matched on age and non-verbal IQ. There was leftward SF and anterior parietal asymmetry, and rightward posterior parietal asymmetry, across groups. There were associations between SF and parietal asymmetries, with slight group differences. Typical SF asymmetry was associated with typical anterior and posterior parietal asymmetry, in both groups. In the atypical SF asymmetry group, controls had atypical parietal asymmetry, whereas in ASD there were more equal numbers of individuals with typical as atypical anterior parietal asymmetry. We did not find significant anatomical-behavioral associations. Our findings of more individuals in the ASD group having a dissociation between cortical asymmetries warrants further investigation of these subgroups and emphasizes the importance of investigating anatomical relationships in addition to group differences in individual regions.

Prefrontal and occipital asymmetry and volume in boys with autism spectrum disorder.

OBJECTIVE: To examine prefrontal and occipital asymmetry (brain torque) in boys with autism spectrum disorder (ASD) and controls. A secondary aim was to study age-related changes in gray and white matter volume. BACKGROUND: Several studies have found atypical early cortical development in ASD. Atypical brain torque, defined as a greater-than-normal left prefrontal and right occipital asymmetry, has been found in some studies of children and adults with ASD. This configuration may be an early neural marker of ASD risk. METHODS: We studied 24 right-handed boys with ASD and 27 typically developing right-handed boys, 7 to 15 years old, obtaining neuropsychological profiles and measuring prefrontal and occipital volumes on magnetic resonance images. RESULTS: Most participants had the expected rightward prefrontal and leftward occipital asymmetry, with no group differences in direction or degree of asymmetry. We found a trend toward larger prefrontal volume in the ASD group than in the controls. The controls also had a trend toward differences in age associations, correlating with total and left prefrontal white matter volumes. CONCLUSIONS: Our findings suggest that atypical brain torque may not be a neural signature of ASD, although our sample was limited to high-functioning, right-handed boys. Our results provide support for aberrant cortical development in ASD, continuing into adolescence, with prefrontal regions being disproportionally affected.

Language laterality in autism spectrum disorder and typical controls: a functional, volumetric, and diffusion tensor MRI study.

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. Fourteen 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.

Age-Related Changes in the Anatomy of Language Regions in Autism Spectrum Disorder.

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.

fMRI activation during a language task in adolescents with ASD.

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.

Effective and structural connectivity in the human auditory cortex.

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 level-dependent (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.

Anatomical asymmetries of anterior perisylvian speech-language regions.

Anterior cortical perisylvian areas important for speech and language functions include the pars triangularis (PTR), comprised of heteromodal association cortex, and the pars opercularis (POP), comprised of motor association cortex. The anatomy of these frontal language regions has not been well studied in large samples, however in smaller samples, leftward asymmetry of these regions has been found. Sex-linked differences have also been suggested, with bilateral activation of frontal language areas in women and leftward activation in men. We used volumetric MRI methods to measure the gray matter volume of the PTR, POP, and diagonal sulcus (DS) in 60 healthy right-handed adults and examined the distribution of asymmetry of these regions. Sex-linked differences in volume and asymmetry of anterior speech regions were also examined. For the PTR, there was a slight leftward asymmetry, however for the POP+DS, there was a slight rightward asymmetry. The DS was present slightly more often in the right hemisphere than in the left hemisphere and its frequency was similar in men and women. There were no significant sex-linked differences in volume or asymmetry for any of these frontal areas. More studies are necessary, looking at the anatomy of anterior language regions in large samples and examining the relationship between anatomy and function.

Function and connectivity in human primary auditory cortex: a combined fMRI and DTI study at 3 Tesla.

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.

Lobar asymmetries in subtypes of dyslexic and control subjects.

Reading involves phonologic decoding, in which readers "sound out" a word; orthographic decoding, in which readers recognize a word visually, as in "sight reading"; and comprehension. Because reading can involve multiple processes, dyslexia might be a heterogeneous disorder. This study investigated behavior and gross lobar anatomy in subtypes of dyslexic and control subjects. Subjects aged 18 to 25 years with identified reading problems and a group of healthy controls were given cognitive and behavioral tests and volumetric brain magnetic resonance imaging (MRI). Because atypical cerebral laterality has been proposed as a potential neural risk for dyslexia, dyslexic and control subjects were compared on anatomy of gross lobar regions. On asymmetry quotients, no significant differences were found between groups. Examination of the percentage of total brain volume of each structure revealed that control and dyslexic subjects were significantly different (P = .018). Dyslexic subjects had a larger percentage of brain volume than did the controls in the areas of total prefrontal (P = .003; 9.30% larger) and superior prefrontal (P = .004; 11.48% larger region). A Pearson correlation was performed to investigate whether a relationship existed between behavioral measures and either volumes of total prefrontal and total occipital regions or asymmetry quotients. A significant positive relationship between the left total occipital and word identification performance existed (R = .452, P = .045). Because it is believed by some that dyslexia occurs in varying degrees of severity, and because one of the research questions in this study is whether anatomy relates to severity or to distinct biologic groups, subjects were grouped according to both the nature and distinct pattern of reading or language performance and the degree of deficit. A battery of reading tests revealed five clinical subgroups of control (two) and dyslexic (three) subjects. These subgroups were statistically different on all cognitive and behavioral measures. When asymmetry was investigated across subgroups, significant differences between subgroups were found at the multivariate level (P = .043). Only the phonologic deficit groups (weak phonologic controls, phonologic deficit dyslexic subjects) had atypical asymmetry patterns. This finding suggests that lack of subtyping could have confounded earlier studies and that anomalous asymmetry might be related to phonologic dyslexia, whereas other subtypes might be reflective of environmental factors. Examination of volume at the subgroup level also showed differences between subgroups that might have implications for the nature of compensation. This study supports the concept that anomalous anatomy might reflect anomalous functional cerebral laterality, which could be a risk factor for developmental dyslexia, varying according to the nature of the deficit.

Variability in perisylvian brain anatomy in healthy adults.

Gray matter volumes of Heschl's gyrus (HG), planum temporale (PT), pars triangularis (PTR), and pars opercularis were measured on MRI in 48 healthy right-handers. There was the expected leftward PT asymmetry in 70.8%, and leftward PTR asymmetry in 64.6% of the sample. When asymmetry patterns within individuals were examined, there was not one typical pattern, rather several typical configurations were found. In addition, some combinations of asymmetry did not exist in our sample suggesting that some perisylvian anatomical configurations may provide a more suitable neural substrate for the development of language than others. There were also sex differences in HG. Men had rightward asymmetry and women demonstrated leftward asymmetry, due to women having smaller right HG, compared to men.

Sex-linked differences in the anatomy of the perisylvian language cortex: a volumetric MRI study of gray matter volumes.

Perisylvian regions important for auditory processing include Heschl's gyrus (HG), the planum temporale (PT), the posterior superior temporal gyrus (pSTG), and the posterior ascending ramus (PAR). Sex-linked differences in language functions and anatomy have been suggested. To examine sex-linked differences, the authors used MRI to measure HG, PT, pSTG, and PAR volumes. Sex differences were found in right HG and right pSTG volumes but not in the left volumes of these structures. For the PT, there were sex differences in asymmetry; women exhibited leftward asymmetry of the PT, whereas men did not exhibit PT asymmetry. These findings suggest that there are sex-linked differences in the anatomy of primary and association auditory cortices.