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It has been established that typically developing individuals have a bias to attend to facial information in the left visual field (LVF) more than in the right visual field (RVF). This bias is thought to arise from the right hemisphere’s advantage for processing facial information, with evidence suggesting it to be driven by the configural demands of face processing. Considering research showing that individuals with autism have impaired face processing abilities, with marked deficits in configural processing, it was hypothesized that they would not demonstrate a LVF bias for faces. Eye-tracking technology was used to show that, individuals with autism were not spontaneously biased to facial information in the LVF, in contrast to a control group, while discriminating facial gender.

This functional magnetic resonance imaging study compared the neural activation patterns of 18 high-functioning individuals with autism and 18 IQ-matched neurotypical control participants as they learned to perform a social judgment task. Participants learned to identify liars among pairs of computer-animated avatars uttering the same sentence but with different facial and vocal expressions, namely those that have previously been associated with lying versus truth-telling. Despite showing a behavioral learning effect similar to the control group, the autism group did not show the same pattern of decreased activation in cortical association areas as they learned the task. Furthermore, the autism group showed a significantly smaller increase in interregion synchronization of activation (functional connectivity) with learning than did the control group. Finally, the autism group had decreased structural connectivity as measured by corpus callosum size, and this measure was reliably related to functional connectivity measures. The findings suggest that cortical underconnectivity in autism may constrain the ability of the brain to rapidly adapt during learning.

Prior studies have indicated brain abnormalities underlying social processing in autism, but no fMRI study has specifically addressed the differential processing of direct and averted gaze, a critical social cue. Fifteen adolescents and adults with autism and 14 typically developing comparison participants viewed dynamic virtual-reality videos depicting a simple but realistic social scenario, in which an approaching male figure maintained either direct or averted gaze. Significant group by condition interactions reflecting differential responses to direct versus averted gaze in people with autism relative to typically developing individuals were identified in the right temporoparietal junction, right anterior insula, left lateral occipital cortex, and left dorsolateral prefrontal cortex. Our results provide initial evidence regarding brain mechanisms underlying the processing of gaze direction during simple social encounters, providing new insight into the social deficits in individuals with autism.

Multiple studies suggest that the corpus callosum in patients with autism is reduced in size. This study attempts to elucidate the nature of this morphometric abnormality by analyzing the shape of this structure in 17 high-functioning patients with autism and an equal number of comparison participants matched for age, sex, IQ, and handedness. The corpus callosum was segmented from T1 weighted images acquired with a Siemens 1.5 T scanner. Transformed coordinates of the curvilinear axis were aggregated into a parametric map and compared across series to derive regions of statistical significance. Our results indicate that a reduction in size of the corpus callosum occurs over all of its subdivisions (genu, body, splenium) in patients with autism. Since the commissural fibers that traverse the different anatomical compartments of the corpus callosum originate in disparate brain regions our results suggest the presence of widely distributed cortical abnormalities in people with autism.

There is a growing amount of evidence suggesting that individuals with autism have difficulty with face processing. One basic cognitive ability that may underlie face processing difficulties is the ability to abstract a prototype. The current study examined prototype formation with natural faces using eye-tracking in high-functioning adults with autism and matched controls. Individuals with autism were found to have significant difficulty forming prototypes of natural faces. The eye-tracking data did not reveal any between group differences in the general pattern of attention to the faces, indicating that these difficulties were not due to attentional factors. Results are consistent with previous studies that have found a deficit in prototype formation and extend these deficits to natural faces.

Cortical and central white matter (WM) volumes were measured to assess short- and long-range connectivity in autism, respectively. Subjects included 23 boys with autism and 23 matched controls, all without intellectual disability. Magnetic resonance imaging data obtained at 1.5 T were analyzed using BRAINS2 software (University of Iowa, Iowa City, IA, USA). Central WM volume was quantified by subtracting cortical from supratentorial WM volumes. Reduced central WM volume was observed in the autism group. IQ was higher in controls with no observed correlations between WM volumes and IQ. This preliminary evidence of reduced central WM volume in autism suggests abnormal long-range connectivity.

Autism Spectrum Disorders (ASD) are associated with abnormalities in face memory, which evidence suggests has a protracted development through adolescence. The development of face memory in people with and without ASD, from 9 to 29 years old, was examined using the Cambridge Face Memory Test (CFMT). Results indicate that the developmental improvement evident from adolescence to adulthood typically was not apparent in individuals with ASD. While children and adolescents with ASD performed similarly to typically developing individuals comparable in age and IQ, adults with ASD displayed limitations on the CFMT. The pattern of performance was constant across conditions despite differences in the timing of the presentation and delay. This atypical development in ASD is consistent with the view that the processing of complex visual stimuli continues to develop through adolescence, along with the function and structure of the temporal lobes, but that this process is disrupted in ASD. This result underscores the importance of characterizing adolescent development for understanding ASD, and suggests additional opportunities for intervention.

Etiology, pathophysiology, and diagnosis of autism spectrum disorder. Virtual Mentor is a monthly bioethics journal published by the American Medical Association.

Individuals with high-functioning autism sometimes exhibit intact or superior performance on visuospatial tasks, in contrast to impaired functioning in other domains such as language comprehension, executive tasks, and social functions. The goal of the current study was to investigate the neural bases of preserved visuospatial processing in high-functioning autism from the perspective of the cortical underconnectivity theory. We used a combination of behavioral, functional magnetic resonance imaging (fMRI), functional connectivity, and corpus callosum morphometric methodological tools. Thirteen participants with high-functioning autism and thirteen controls (age-, IQ-, and gender-matched) were scanned while performing an Embedded Figures Task (EFT). Despite the ability of the autism group to attain behavioral performance comparable to the control group, the brain imaging results revealed several group differences consistent with the cortical underconnectivity account of autism. First, relative to controls, the autism group showed less activation in left dorsolateral prefrontal and inferior parietal areas and more activation in visuospatial (bilateral superior parietal extending to inferior parietal and right occipital) areas. Second, the autism group demonstrated lower functional connectivity between higher-order working memory/executive areas and visuospatial regions (between frontal and parietal-occipital). Third, the size of the corpus callosum (an index of anatomical connectivity) was positively correlated with frontal-posterior (parietal and occipital) functional connectivity in the autism group. Thus, even in the visuospatial domain, where preserved performance among people with autism is observed, the neuroimaging signatures of cortical underconnectivity persist.

The validity of Asperger disorder as a distinct syndrome from autism is unclear partly because of the paucity of differentiating neurobiological evidence. Frontal lobe cortical folding between these disorders was compared using the gyrification index. Twenty-three boys underwent structural magnetic resonance imaging: 6 with high-functioning autism, 9 with Asperger disorder, and 8 controls. Using the first coronal slice anterior to the corpus callosum, total and outer cortical contours were traced to calculate the gyrification index. This index was also calculated for superior and inferior regions to examine dorsolateral prefrontal and orbitofrontal cortices, respectively. Analysis of variance revealed differences in the left inferior gyrification index, which was higher in the autism group compared with Asperger and control groups. There were no differences in age, intelligence quotient, and brain volume. These preliminary findings suggest that cortical folding may be abnormally high in the frontal lobe in autism but not Asperger disorder, suggesting distinct frontal lobe neuropathology.

Functional magnetic resonance imaging studies have had a profound impact on the delineation of the neurobiologic basis for autism. Advances in fMRI technology for investigating functional connectivity, resting state connectivity, and a default mode network have provided further detail about disturbances in brain organization and brain-behavior relationships in autism to be reviewed in this article.Recent fMRI studies have provided evidence of enhanced activation and connectivity of posterior, or parietal-occipital, networks and enhanced reliance on visuospatial abilities for visual and verbal reasoning in high functioning individuals with autism. Evidence also indicates altered activation in frontostriatal networks for cognitive control, particularly involving anterior cingulate cortex, and altered connectivity in the resting state and the default mode network. The findings suggest that the specialization of many cortical networks of the human brain has failed to develop fully in high functioning individuals with autism.This research provides a growing specification of to the neurobiologic basis for this complex syndrome and for the co-occurrence of the signs and symptoms as a syndrome. With this knowledge has come new neurobiologically based opportunities for intervention.

Autism or autism spectrum disorder (ASD) is usually thought of as a behavioral and social communication impairment. However, it is a broad-based neurodevelopmental or brain-based disorder that is the result of genetic events that occur prior to birth with widespread effects on cognitive and socio-emotional development (Geschwind, 2009). Autism clearly affects social functioning, but it has an impact on the development and use of language that extends beyond pragmatics.

Little is known regarding metacognition in individuals with autism. Specifically, it is unclear how individuals with autism think about their own mental states. The current study assessed memory awareness during a facial recognition task. High-functioning children (M = 13.1 years, n = 18) and adults (M = 27.5 years, n = 16) with autism matched with typically developing children (M = 14.3 years, n = 13) and adults (M = 26.9 years, n = 15) were tested. Children with autism demonstrated less accurate memory awareness for faces and less reliable differentiation between their confidence ratings compared to typically developing children. Subtle impairments in memory awareness for faces were also evident in adults with autism. Results indicate that broader metacognitive deficits may exist in individuals with autism, possibly contributing to other known impairments.

Prototype formation is a critical skill for category learning. Research suggests that individuals with autism may have a deficit in prototype formation of some objects; however, results are mixed. The current study used a natural category, faces, to further examine prototype formation in high-functioning individuals with autism. High-functioning children (age 8–13 years) and adults with autism (age 17–53 years) and matched controls were tested in a facial prototype formation task that has been used to test prototype formation abilities in typically developing infants and adults (Strauss, 1979). Participants were familiarized to a series of faces depicting subtle variations in the spatial distance of facial features, and were then given a forced choice familiarity test between the mean prototype and the mode prototype. Overall, individuals in the autism group were significantly less likely to select the mean prototype face. Even though the children with autism showed this difference in prototype formation, this pattern was driven primarily by the adults, because the adults with autism were approximately 4 times less likely to select the mean prototype than were the control adults. These results provide further evidence that individuals with autism have difficulty abstracting subtle spatial information that is necessary not only for the formation of a mean prototype, but also for categorizing faces and objects.

Background Autism is a developmental neurobiologic disorder associated with structural and functional abnormalities in several brain regions including the cerebral cortex. This longitudinal study examined developmental changes in brain volume and cortical thickness (CT) using magnetic resonance imaging (MRI) in children with autism. Methods MRI scans and behavioral measures were obtained at baseline and after a 30-month interval in a sample of male subjects with autism (n = 18) and healthy age-, and sex-matched control subjects (n = 16) between ages 8 and 12 years at baseline. Results No differences in brain volumes were observed between the autism and control subjects at baseline or follow-up. However, differences in total gray matter volumes were observed over time with significantly greater decreases in the autism group compared with control subjects. Differences in CT were observed over time with greater decreases in the autism group compared with control subjects in several brain regions including the frontal lobe. When accounting for multiple comparisons, differences between the two groups became nonsignificant except for changes in occipital CT. Furthermore, associations were observed between several clinical features and changes in CT with greater thinning of the cortex being correlated with more severe symptomatology. Conclusions Findings from this study provide preliminary evidence for age-related changes in gray matter volume and CT in children with autism that are associated with symptoms severity. Future longitudinal studies of larger sample sizes are needed to evaluate developmental changes and examine the relationships between structural abnormalities and clinical expressions of the disorder.

Background Procedural learning is an implicit process in which a behavioral response is refined through repeated performance. Neural systems supporting this cognitive process include specific frontostriatal systems responsible for the preparation and timing of planned motor responses. Evaluating performance on procedural learning tasks can provide unique information about neurodevelopmental disorders in which frontostriatal disturbances have been reported, such as autism. Methods Fifty-two individuals with autism and 54 age-, IQ-, and gender-matched healthy individuals performed an oculomotor serial reaction time task and a sensorimotor control task. Results Whereas the rate of procedural learning and the precision of planned motor responses were unimpaired in autism, a lateralized alteration in the ability to time predictive responses was observed. Rightward saccadic responses were speeded in individuals with autism relative to healthy control subjects. Conclusions Speeded rightward predictive saccades suggest atypical functioning of left hemisphere striatal chronometric systems in autism.

Autism spectrum disorders (ASDs) are childhood neurodevelopmental disorders with complex genetic origins. Previous studies focusing on candidate genes or genomic regions have identified several copy number variations (CNVs) that are associated with an increased risk of ASDs. Here we present the results from a whole-genome CNV study on a cohort of 859 ASD cases and 1,409 healthy children of European ancestry who were genotyped with approximately 550,000 single nucleotide polymorphism markers, in an attempt to comprehensively identify CNVs conferring susceptibility to ASDs. Positive findings were evaluated in an independent cohort of 1,336 ASD cases and 1,110 controls of European ancestry. Besides previously reported ASD candidate genes, such as NRXN1 (ref. 10) and CNTN4 (refs 11, 12), several new susceptibility genes encoding neuronal cell-adhesion molecules, including NLGN1 and ASTN2, were enriched with CNVs in ASD cases compared to controls (P = 9.5 x 10(-3)). Furthermore, CNVs within or surrounding genes involved in the ubiquitin pathways, including UBE3A, PARK2, RFWD2 and FBXO40, were affected by CNVs not observed in controls (P = 3.3 x 10(-3)). We also identified duplications 55 kilobases upstream of complementary DNA AK123120 (P = 3.6 x 10(-6)). Although these variants may be individually rare, they target genes involved in neuronal cell-adhesion or ubiquitin degradation, indicating that these two important gene networks expressed within the central nervous system may contribute to the genetic susceptibility of ASD.

The corpus callosum has recently been considered as an index of interhemispheric connectivity. This study applied a novel volumetric method to examine the size of the corpus callosum in 32 individuals with autism and 34 age-, gender- and IQ-matched controls and to investigate the relationship between this structure and cognitive measures linked to interhemispheric functioning. Participants with autism displayed reductions in total corpus callosum volume and in several of its subdivisions. Relationships were also observed between volumetric alterations and performance on several cognitive tests including the Tower of Hanoi test. These findings provide further evidence for volumetric alterations in the corpus callosum in autism, but warrant additional studies examining the relationship of this structure and specific measures of interhemispheric connectivity.

BackgroundAlthough several studies have examined brainstem volume in autism, results have been mixed and no investigation has specifically measured gray- and white-matter structures. The aim of this investigation was to assess gray- and white-matter volumes in children with autism.MethodSubjects included 22 right-handed, non-mentally retarded boys with autism and 22 gender- and age-matched controls. Magnetic resonance imaging (MRI) scans were obtained using a 1.5-T scanner and volumetric measurements were performed using the BRAINS2 software package. Gray- and white-matter volumes were measured using a semi-automated segmentation process.ResultsThere were no significant differences in age and total brain volume (TBV) between the two groups but full-scale IQ was higher in controls. A decrease in brainstem gray-matter volume was observed in the autism group before and after controlling for TBV. No significant differences were observed in white-matter volume. A significant relationship was observed between brainstem gray-matter volume and oral sensory sensitivity as measured by the Sensory Profile Questionnaire (SPQ).ConclusionsFindings from this study are suggestive of brainstem abnormalities in autism involving gray-matter structures with evidence supporting the existence of a relationship between these alterations and sensory deficits. These results are consistent with previous investigations and support the existence of disturbances in brainstem circuitry thought to be implicated in the sensory dysfunction observed in autism.

Impairments in face processing are a relatively recent discovery in autism, but have quickly become a widely accepted aspect of the behavioral profile. The impairment goes beyond face recognition and involves difficulty in remembering faces (Boucher & Lewis, 1992), processing facial expressions (Ashwin, Baron-Cohen, Weelwright, O’Riordan, & Bullmore, 2006), and knowing which components of faces convey especially important communicative information (Joseph & Tanaka, 2003). Not surprisingly, these deficits contribute significantly to social dysfunction in autism. Despite the growing empirical evidence, the origin of the face processing deficits in autism remains unknown. One view suggests that individuals with autism have a decreased motivation to attend to social stimuli, which limits the ability to gain expertise in face processing (Dawson, et al., 2002; Grelotti, Gauthier, & Schultz, 2002). This social motivation impairment should not affect the recognition of non-social objects. Another view proposes that face-processing deficits result from atypical perceptual processing (e.g. enhanced processing of local features; Happe & Frith, 2006; Mottron, Dawson, Soulieres, Hubert, & Burack, 2006), which limits the ability to develop expertise with any class of visual objects (Behrmann, et al., 2006a; Behrmann, Thomas, & Humphreys, 2006b;). This failure to develop expertise disproportionately impacts processing of perceptually homogenous objects since fine-grained discrimination and representation of the subtle metric variations between the constituent features, also called the configural properties of these stimuli (Diamond & Carey, 1986), is required to differentiate these similar objects. Faces are a paradigmatic class of such objects and the bias to focus on local features may impede the processing of the relational properties needed for individuating faces and other perceptually similar non-face objects. To distinguish between these two potential origins of the face-processing deficit in autism, we evaluated whether individuals with autism have difficulty developing perceptual expertise and whether any such decrement is specific to faces or extends to other objects. We employed two empirical definitions of visuoperceptual expertise. First, we evaluated children’s and adult’s sensitivity to face inversion: typically-developing (TD) children and adults are slower and less accurate to recognize an inverted face (Valentine, 1988; Yin, 1969). Sensitivity to inversion is considered a measure of visuoperceptual expertise (Carey & Diamond, 1977) because: 1) the magnitude of the face inversion effect (FIE) increases with age, resulting from increasing knowledge about the spatial-relational properties of faces (see Carey 1981; Flin 1983); 2) it is evident in experts recognizing other objects of expertise (e.g., dogs for dog experts; Diamond & Carey, 1986) and in adults trained to recognize a novel class of objects (Gauthier & Tarr, 1996), and 3) it is less evident for other classes of objects that are not typically recognized at the individual level (Diamond & Carey, 1986; Yin, 1969). However, there are disparate findings about whether individuals with autism show an intact FIE. Several studies have reported the absence of a FIE and superior performance on inverted face recognition in children and adolescents with autism compared to TD individuals (Hobson, Ouston, & Lee, 1988; Langdell, 1978; McPartland, et al., 2004; Tantam, Monagham, Nicholson, & Stirling, 1989). Other studies have found evidence for a spared FIE in children and adolescents with autism (Joseph & Tanaka, 2003; Lahaie, et al., 2006; Teunisse & de Gelder, 2003). Part of the discrepancy in these findings may be related to the inclusion of broad age ranges, which may have masked the ability to observe developmental changes in the FIE, heterogeneity of the sample (Barton et al., 2007) and/or the use of stimuli in which simultaneous changes in orientation and facial expression are present. To circumvent these potential confounds, we used naturalistic faces with neutral expressions to evaluate the FIE from childhood (ages 8–13) to adulthood in relatively high-functioning individuals with autism (HFA) and age-matched typically-developing participants (TD). Our second measure of face expertise, previously used to evaluate deficits in expert face and object recognition in adults with acquired visual agnosia (Gauthier, Behrmann, & Tarr, 1999), involved manipulating the level of categorization at which faces are recognized. Most objects are recognized at the “basic” level of abstraction (e.g., dog versus chair) and can be distinguished by unique features or configurations of features (Rosch 1978; Tanaka & Taylor, 1991). However, all objects can be recognized at more “subordinate” levels (e.g., cocker spaniel vs poodle), where all exemplars share similar parts in a similar basic configuration but differ in the spatial relations within this basic configuration. It is at this level that sensitivity to configural information is critical for making subordinate-level discriminations between exemplars (Diamond & Carey, 1986). Expertise with any particular object class is indicated by the ability to recognize objects equally fast at the individual level (e.g., Joey’s face), where featural differences are less diagnostic than configural properties for recognition, and at the basic level, where featural differences are very discriminating (Gauthier et al., 1999). Recent studies of adults with autism suggest that the ability to recognize faces at the individual level is disproportionately slower than at the basic level, indicating a lack of expertise (Behrmann, et al., 2006a). Interestingly, this difficulty was not limited to faces; in fact, adults with autism showed similar difficulties in discriminating common and novel objects at the individual levels, indicating that atypical face processing may be related to a more general abnormality in visuoperceptual processing. In the current study, we evaluated the developmental trajectory of the ability to discriminate faces, homogeneous novel objects known as Greebles, and common objects at the individual level in HFA and TD children and adults.

Background Inhibiting prepotent responses is critical to optimal cognitive and behavioral function across many domains. Several behavioral studies have investigated response inhibition in autism, and the findings varied according to the components involved in inhibition. There has been only one published functional magnetic resonance imaging (fMRI) study so far on inhibition in autism, which found greater activation in participants with autism than control participants. Methods This study investigated the neural basis of response inhibition in 12 high-functioning adults with autism and 12 age- and intelligence quotient (IQ)-matched control participants during a simple response inhibition task and an inhibition task involving working memory. Results In both inhibition tasks, the participants with autism showed less brain activation than control participants in areas often found to be active in response inhibition tasks, namely the anterior cingulate cortex. In the more demanding inhibition condition, involving working memory, the participants with autism showed more activation than control participants in the premotor areas. In addition to the activation differences, the participants with autism showed lower levels of synchronization between the inhibition network (anterior cingulate gyrus, middle cingulate gyrus, and insula) and the right middle and inferior frontal and right inferior parietal regions. Conclusions The results indicate that the inhibition circuitry in the autism group is activated atypically and is less synchronized, leaving inhibition to be accomplished by strategic control rather than automatically. At the behavioral level, there was no difference between the groups.

The objective of this study was to examine the relationship between thalamic volume and brain size in individuals with Asperger's disorder (ASP). Volumetric measurements of the thalamus were performed on MRI scans obtained from 12 individuals with ASP (age range: 10-35 years) and 12 healthy controls (age range: 9-33 years). A positive correlation was found between total brain volume and thalamic size in controls, but not in ASP subjects. This occurred in the absence of differences in mean thalamic volumes between the study groups. Findings from this investigation point to an abnormal relationship between the thalamus and its projection areas in ASP and are consistent with similar studies in autism, supporting that these disorders are qualitatively similar and possibly quantitatively different.

Recent evidence has implicated the orbitofrontal cortex (OFC) in the pathophysiology of social deficits in autism. An MRI-based morphometric study of the OFC was conducted involving 11 children with autism (age range 8.1–12.7 years) and 18 healthy, age-matched controls (age range 8.9–12.8 years). Decreased grey matter volume in the right lateral OFC in the patient group was found, and correlations were observed between social deficits and white, but not grey, matter structures of the OFC. These findings support the role of OFC in autism and warrant further investigations of this structure using structural and functional methodologies.

It is unclear whether individuals with autism are impaired at recognizing basic facial expressions, and whether, if any impairment exists, it applies to expression processing in general, or to certain expressions, in particular. To evaluate these alternatives, we adopted a fine-grained analysis of facial expression processing in autism. Specifically, we used the ‘facial expression megamix’ paradigm [Young, A. W., Rowland, D., Calder, A. J, Etcoff, N. L., Seth, A., & Perrett, D. I. (1997). Facial expression megamix: Tests of dimensional and category accounts of emotion recognition Cognition and Emotion, 14, 39–60] in which adults with autism and a typically developing comparison group performed a six alternative forced-choice response to morphs of all possible combinations of the six basic expressions identified by Ekman [Ekman, P. (1972). Universals and cultural differences in facial expressions of emotion. In J. K. Cole (Ed.), Nebraska symposium on motivation: vol. 1971, (pp. 207–283). Lincoln, Nebraska: University of Nebraska Press] (happiness, sadness, disgust, anger, fear and surprise). Clear differences were evident between the two groups, most obviously in the recognition of fear, but also in the recognition of disgust and happiness. A second experiment demonstrated that individuals with autism are able to discriminate between different emotional images and suggests that low-level perceptual difficulties do not underlie the difficulties with emotion recognition.

Autism and schizophrenia share multiple phenotypic and genotypic markers, and there is ongoing debate regarding the relationship of these two disorders. To examine whether cortical dynamics are similar across these disorders, we directly compared fMRI responses to visual, somatosensory and auditory stimuli in adults with autism (N=15), with schizophrenia (N=15), and matched controls (N=15). All participants completed a one-back letter detection task presented at fixation (to control attention) while task-irrelevant sensory stimulation was delivered to the different modalities. We focused specifically on the response amplitudes and the variability in sensory fMRI responses of the two groups, given the evidence of greater trial-to-trial variability in adults with autism. Both autism and schizophrenia individuals showed weaker signal-to-noise ratios (SNR) in sensory-evoked responses compared to controls (d>0.42), but for different reasons. For the autism group, the fMRI response amplitudes were indistinguishable from controls but were more variable trial-to-trial (d=0.47). For the schizophrenia group, response amplitudes were smaller compared to autism (d=0.44) and control groups (d=0.74), but were not significantly more variable (d

Background Theory-of-mind (ToM), the ability to infer people’s thoughts and feelings, is a pivotal skill in effective social interactions. Individuals with autism spectrum disorders (ASD) have been found to have altered ToM skills, which significantly impacts the quality of their social interactions. Neuroimaging studies have reported altered activation of the ToM cortical network, especially in adults with autism, yet little is known about the brain responses underlying ToM in younger individuals with ASD. This functional magnetic resonance imaging (fMRI) study investigated the neural mechanisms underlying ToM in high-functioning children and adolescents with ASD and matched typically developing (TD) peers. Methods fMRI data were acquired from 13 participants with ASD and 13 TD control participants while they watched animations involving two “interacting” geometrical shapes. Results Participants with ASD showed significantly reduced activation, relative to TD controls, in regions considered part of the ToM network, the mirror network, and the cerebellum. Functional connectivity analyses revealed underconnectivity between frontal and posterior regions during task performance in the ASD participants. Conclusions Overall, the findings of this study reveal disruptions in the brain circuitry underlying ToM in ASD at multiple levels, including decreased activation and decreased functional connectivity. Electronic supplementary material The online version of this article (doi:10.1186/s13229-015-0052-x) contains supplementary material, which is available to authorized users.

Inflexible behavior is a core characteristic of autism spectrum disorder (ASD), but its underlying cause is unknown. Using a perceptual learning protocol, we observed initially efficient learning in ASD that was followed by anomalously poor learning when the location of the target was changed (over-specificity). Reducing stimulus repetition eliminated over-specificity. Our results indicate that inflexible behavior may be evident ubiquitously in ASD, even in sensory learning, but can be circumvented by specifically designed stimulation protocols.

More than 20 years ago, Minshew and colleagues proposed the Complex Information Processing model of autism in which the impairment is characterized as a generalized deficit involving multiple modalities and cognitive domains that depend on distributed cortical systems responsible for higher order abilities. Subsequent behavioral work revealed a related dissociation between concept formation and concept identification in autism suggesting the lack of an underlying organizational structure to manage increases in processing loads. The results of a recent study supported the impact of this relative weakness in conceptual reasoning on adaptive functioning in children and adults with autism. In this study, we provide further evidence of the difficulty relatively able older adolescents and adults with autism have with conceptual reasoning and provide evidence that this characterizes their difference from age- and ability-matched controls with typical development better than their differences in language. For verbal adults with autism, language may serve as a bootstrap or compensatory mechanism for learning but cannot overcome an inherent weakness in concept formation that makes information processing challenging as task demands increase.

Studies investigating inferential reasoning in autism spectrum disorder (ASD) have focused on the ability to make socially-related inferences or inferences more generally. Important variables for intervention planning such as whether inferences depend on physical experiences or the nature of social information have received less consideration. A measure of bridging inferences of physical causation, mental states, and emotional states was administered to older children, adolescents, and adults with and without ASD. The ASD group had more difficulty making inferences, particularly related to emotional understanding. Results suggest that individuals with ASD may not have the stored experiential knowledge that specific inferences depend upon or have difficulties accessing relevant experiences due to linguistic limitations. Further research is needed to tease these elements apart.

Although sensory hypersensitivity is not one of the triad of core symptoms in autism, changes in sensory responses are a well-known and sometimes even debilitating aspect of the disorder. Here, we rev

A wide range of abilities was assessed in 56 high-functioning children with autism and 56 age- and IQ-matched controls. Stepwise discriminant analyses produced good group discrimination for sensory-perceptual, motor, complex language, and complex memory domains but lower agreement for the reasoning domain than previously obtained for adults. Group discrimination did not occur for attention, simple language, simple memory, and visuospatial domains. Findings provide additional support for a complex information-processing model for autism, previously based on adult data, demonstrating a pattern across domains of selective impairments on measures with high demands for integration of information and sparing when demands were low. Children as compared to adults with autism exhibited more prominent sensory-perceptual symptoms and less pronounced reasoning deficits reflecting brain maturation.

Previous studies have reported working memory deficits in autism, but this finding has been inconsistent. One possibility is that deficits in this domain may be present only when working memory load exceeds some limited capacity. High-functioning individuals with autism performed the CANTAB computerized test of spatial working memory. Individuals with autism made more errors than a matched group of typically developing controls on this task, and were less likely to consistently use a specific organized search strategy to complete the task. Overall, these results demonstrate reduced spatial working memory abilities in autism, and extend previous findings by demonstrating that these deficits are significant when tasks impose heavier demands on working memory.

We performed a genome-wide linkage scan using highly polymorphic microsatellite markers. To minimize genetic heterogeneity, we focused on sibpairs meeting the strict diagnosis of autism. In our primary analyses, we observed a strong linkage signal (P=0.0006, 133.16 cM) on chromosome 7q at a location coincident with other linkage studies. When a more relaxed diagnostic criteria was used, linkage evidence at this location was weaker (P=0.01). The sample was stratified into families with only male affected subjects (MO) and families with at least one female affected subject (FC). The strongest signal unique to the MO group was on chromosome 11 (P=0.0009, 83.82 cM), and for the FC group on chromosome 4 (P=0.002, 111.41 cM). We also divided the sample into regression positive and regression negative families. The regression-positive group showed modest linkage signals on chromosomes 10 (P=0.003, 0 cM) and 14 (P=0.005, 104.2 cM). More significant peaks were seen in the regression negative group on chromosomes 3 (P=0.0002, 140.06 cM) and 4 (P=0.0005, 111.41 cM). Finally, we used language acquisition data as a quantitative trait in our linkage analysis and observed a chromosome 9 signal (149.01 cM) of P=0.00006 and an empirical P-value of 0.0008 at the same location. Our work provides strong conformation for an autism locus on 7q and suggestive evidence for several other chromosomal locations. Diagnostic specificity and detailed analysis of the autism phenotype is critical for identifying autism loci.

The brain activation of a group of high-functioning autistic participants was measured using functional magnetic resonance imaging during the performance of a Tower of London task, in comparison with a control group matched with respect to intelligent quotient, age, and gender. The 2 groups generally activated the same cortical areas to similar degrees. However, there were 3 indications of underconnectivity in the group with autism. First, the degree of synchronization (i.e., the functional connectivity or the correlation of the time series of the activation) between the frontal and parietal areas of activation was lower for the autistic than the control participants. Second, relevant parts of the corpus callosum, through which many of the bilaterally activated cortical areas communicate, were smaller in cross-sectional area in the autistic participants. Third, within the autism group but not within the control group, the size of the genu of the corpus callosum was correlated with frontal--parietal functional connectivity. These findings suggest that the neural basis of altered cognition in autism entails a lower degree of integration of information across certain cortical areas resulting from reduced intracortical connectivity. The results add support to a new theory of cortical underconnectivity in autism, which posits a deficit in integration of information at the neural and cognitive levels.

Histopathological, neuroimaging and genetic findings indicate cerebellar abnormalities in autism, but the extent of neurophysiological dysfunction associated with those findings has not been systematically examined. Suppression of intrusive saccades (square wave jerks) and the ability to sustain eccentric gaze, two phenomena requiring intact cerebellar function, were examined in 52 high-functioning individuals with autism and 52 age- and IQ-matched healthy subjects during visual fixation of static central and peripheral targets. Rates of intrusive saccades were not increased in autism during visual fixation, and foveopetal ocular drift was also not increased when subjects held an eccentric gaze. The absence of gross disturbances of visual fixation associated with cerebellar disease in individuals with autism, such as increased square wave jerk rates and foveopetal drift when holding eccentric gaze, indicates that the functional integrity of cerebellar–brainstem networks devoted to oculomotor control is preserved in autism despite reported anatomic variations. However, increased amplitude of intrusive saccades and reduced latency of target refixation after intrusive saccades were observed in individuals with autism, especially when subjects maintained fixation of remembered target locations without sensory guidance. The atypical metrics of intrusive saccades that were observed may be attributable to faulty functional connectivity in cortico-cerebellar networks.

We evaluated the predictive accuracy of short forms of the Wechsler intelligence scales for individuals with high functioning autism. Several short forms were derived from participants who had received the full procedure. Stepwise multiple regression analyses were performed to determine the strength of association between the subtests included in the short form and IQ scores based upon the full test. These analyses were performed for all participants, and also for autism participants with atypical subtest profiles. In all analyses the percentages of explained variance were typically in the .8-.9 range. It was concluded that short forms may be used with good predictive accuracy in individuals with high functioning autism, even when the subtest profile is atypical.

An fMRI study was used to measure the brain activation of a group of adults with high-functioning autism compared to a Full Scale and Verbal IQ and age-matched control group during an n-back working memory task with letters. The behavioral results showed comparable performance, but the fMRI results suggested that the normal controls might use verbal codes to perform the task, while the adults with autism might use visual codes. The control group demonstrated more activation in the left than the right parietal regions, whereas the autism group showed more right lateralized activation in the prefrontal and parietal regions. The autism group also had more activation than the control group in the posterior regions including inferior temporal and occipital regions. The analysis of functional connectivity yielded similar patterns for the two groups with different hemispheric correlations. The temporal profile of the activity in the prefrontal regions was more correlated with the left parietal regions for the control group, whereas it was more correlated with the right parietal regions for the autism group.

The gyrification index (GI), the ratio of total to outer cortical contour, was applied to measure the cerebral folding patterns in autism. GI was examined on a frontal coronal slice obtained from MRI scans of 30 nonmentally retarded individuals with autism and 32 matched healthy controls. In the autistic group, left frontal GI was higher in children and adolescents but not in adults. Cortical folding was decreased bilaterally with age in the total autistic sample but not in controls. These preliminary findings suggest that the gyrification patterns in autism may be abnormal, which could be related to the various cortical anomalies observed in this disorder.

Disturbances in lateral preference in autism are of interest because of their potential to shed light on brain maturational processes in this disorder. Forty-seven autistic individuals with a history of disordered early language development and 22 autistic individuals with normal early language acquisition were matched with 112 healthy individuals and compared on a standardized measure of lateral preference, the Edinburgh Handedness Inventory. Autistic individuals with a history of early language disturbance showed more atypical cerebral dominance than both healthy participants and autistic individuals with normal early language skills. The data indicated maturational disturbances in establishing lateral preference rather than increased rates of left handedness. Atypical establishment of cerebral dominance may be one cause of disordered language development in autism.

Objective: To test the hypothesis that deficits in spatial working memory in autism are due to abnormalities in prefrontal circuitry. Methods: Functional MRI (fMRI) at 3 T was performed in 11 rigorously diagnosed non–mentally retarded autistic and six healthy volunteers while they performed an oculomotor spatial working memory task and a visually guided saccade task. Results: Autistic subjects demonstrated significantly less task-related activation in dorsolateral prefrontal cortex (Brodmann area [BA] 9/46) and posterior cingulate cortex (BA 23) in comparison with healthy subjects during a spatial working memory task. In contrast, activation of autistic individuals was not reduced in other regions comprising the neural circuitry for spatial working memory including the cortical eye fields, anterior cingulate cortex, insula, basal ganglia, thalamus, and lateral cerebellum. Autistic subjects also did not demonstrate reduced activation in any brain regions while performing visually guided saccades. Conclusion: Impairments in executive cognitive processes in autism may be subserved by abnormalities in neocortical circuitry as evidenced by decreased activation in prefrontal and posterior cingulate circuitry during a spatial working memory task.

This article provides an overview of the similarities and distinctions between individuals with autism and those with Asperger syndrome (AS). First, we review the cognitive and neurocognitive profile underlying deficits characteristic of autism spectrum disorders. Particular emphasis is placed on recent comparisons of high-functioning autism to AS on the basis of neuropsychological testing, and implications of neuropsychological profiles for the cognitive deficits and clinical presentation of AS.

Autism and schizophrenia are separate neurodevelopmental disorders that share a number of interpersonal and cognitive deficits. The symptoms of autism first appear during early life while schizophrenic symptoms do not typically appear until adolescence at the earliest. Efforts have been made to characterize the pattern of cognitive function in both disorders, and certain resemblances have become apparent such as deficits in abstract reasoning and the more complex aspects of memory and language. The present study provided a comparison of cognitive function between the two disorders. The autistic sample consisted of well-diagnosed individuals with high-functioning autism (IQ≥70). The schizophrenic sample was divided into four subgroups using Ward's method of cluster analysis. Participants received the Wechsler Adult Intelligence Scale-Revised (WAIS-R), the Halstead Category Test, the Trail Making test, and the Wisconsin Card Sorting test (WCST). The profile of the autism sample was compared with the four schizophrenia cluster profiles. The autism group resembled only one of the schizophrenia clusters, with both showing elevations on the WAIS-R Information and Block Design subtests and depressions on Comprehension and Digit Symbol. It was concluded that individuals with high-functioning autism have a cognitive profile that resembles that of an empirically derived subgroup of schizophrenia patients but that does not resemble profiles found in other schizophrenia subgroups. The pattern itself, marked by a relatively depressed score on the Comprehension subtest among the Verbal subtests and a relatively elevated score on Block Design among the Performance subtests, has been characterized in the past as a prototypic profile for high-functioning autism.

The concept identification and concept formation aspects of abstract reasoning were examined in 90 nonmentally retarded individuals with autism and 107 normal controls. It was hypothesized that pronounced deficits would be found on concept formation tests, whereas performance on concept identification tests would be relatively intact. There was a significant difference between individuals with autism and individuals from a matched control group on all abstract reasoning tasks, but, with the exception of the Wisconsin Card Sorting Test (R. K. Heaton et al., 1993), differences on concept identification tests were not clinically significant. Factor analyses showed that concept formation and concept identification tasks loaded on separate factors in the autism group but not in the control group. Stepwise discriminant function analyses revealed that 2 tests of concept formation correctly classified 78.4% of cases, whereas concept identification tasks did not pass the tolerance test.

This project is focused on conducting the first randomized-controlled trial of Cognitive Enhancement Therapy (CET) in 54 verbal adults with autism spectrum disorders, and assessing the efficacy of this approach in comparison to an active Enriched Supportive Therapy (EST) intervention. Major findings to date include: 1) considerable and broad cognitive impairments at baseline testing in the ASD adults enrolled in this trial (n = 40), and 2) initial evidence of the effectiveness of CET in ameliorating deficits and enhancing adaptive function. Despite normal or higher levels of intelligence, this sample was performing at the 32th percentile on overall neurocognitive function with at least one domain score below the 1% in most individuals, indicating a clear need for cognitive rehabilitation. Preliminary analyses of treatment effects suggest a significant advantage of CET for improving social cognition (d = .63), neurocognition (d = .66), and major role function (d = .76) compared to the EST control condition. In addition, analyses of changes in brain function have indicated significant increases in brain activity supporting theory of mind and emotion regulation abilities in participants treated with CET compared EST. These findings suggest both the need and potential for CET to be a significant treatment advance for verbal adults with autism. Importantly, improvements were found in daily life function and in brain circuitry supporting core abilities.

Multiple hypotheses have been offered to explain the impaired face-processing behavior and the accompanying underlying disruptions in neural circuitry among individuals with autism. We explored the specificity of atypical face-processing activation and potential alterations to fusiform gyrus (FG) morphology as potential underlying mechanisms. Adolescents with high functioning autism (HFA) and age-matched typically developing (TD) adolescents were scanned with sMRI and fMRI as they observed human and animal faces. In spite of exhibiting comparable face recognition behavior, the HFA adolescents evinced hypo-activation throughout the face-processing system in response to unfamiliar human, but not animal, faces. They also exhibited greater activation in affective regions of the face-processing network in response to animal, but not human, faces. Importantly, this atypical pattern of activation in response to human faces was not related to atypical structural properties of the FG. This atypical neural response to human faces in autism may stem from abnormalities in the ability to represent the reward value of social (i.e. conspecific) stimuli.