EEG activation differences in the pre-motor cortex and supplementary motor area between normal individuals with high and low traits of autism

The human mirror neuron system (hMNS) is believed to provide a basic mechanism for social cognition. Event-related desynchronization (ERD) in alpha (8–12 Hz) and low beta band (12–20 Hz) over sensori-motor cortex has been suggested to index mirror neurons' activity. We tested whether autistic traits revealed by high and low scores on the Autistic Quotient (AQ) in the normal population are linked to variations in the electroencephalogram (EEG) over motor, pre-motor cortex and supplementary motor area (SMA) during action observation. Results revealed that in the low AQ group, the pre-motor cortex and SMA were more active during hand action than static hand observation whereas in the high AQ group the same areas were active both during static and hand action observation. In fact participants with high traits of autism showed greater low beta ERD while observing the static hand than those with low traits and this low beta ERD was not significantly different when they watched hand actions. Over primary motor cortex, the classical alpha and low beta ERD during hand actions relative to static hand observation was found across all participants. These findings suggest that the observation–execution matching system works differently according to the degree of autism traits in the normal population and that this is differentiated in terms of the EEG according to scalp site and bandwidth.

Reduced cortico-motor facilitation in a normal sample with high traits of autism

Recent research in social neuroscience proposes a link between mirror neuron system (MNS) and social cognition. The MNS has been proposed to be the neural mechanism underlying action recognition and intention understanding and more broadly social cognition. Pre-motor MNS has been suggested to modulate the motor cortex during action observation. This modulation results in an enhanced cortico-motor excitability reflected in increased motor evoked potentials (MEPs) at the muscle of interest during action observation. Anomalous MNS activity has been reported in the autistic population whose social skills are notably impaired. It is still an open question whether traits of autism in the normal population are linked to the MNS functioning. We measured TMS-induced MEPs in normal individuals with high and low traits of autism as measured by the autistic quotient (AQ), while observing videos of hand or mouth actions, static images of a hand or mouth or a blank screen. No differences were observed between the two while they observed a blank screen. However participants with low traits of autism showed significantly greater MEP amplitudes during observation of hand/mouth actions relative to static hand/mouth stimuli. In contrast, participants with high traits of autism did not show such a MEP amplitude difference between observation of actions and static stimuli. These results are discussed with reference to MNS functioning.

The use of drama to teach social skills in a special school setting for students with autism.

For children with autism, social challenges may be both part of the disability and a barrier to accessing education. This paper reports on a project which used drama to address such challenges by drawing on the social skills of non-autistic peers in a special school setting. The paper demonstrates how drama’s flexibility may be harnessed in order to help students support each other’s development of creative and communicative skills. Focusing on two children in particular, specific examples are given to illustrate how they participated in group work, made imaginative contributions to verbal and physical representations, and engaged with abstract ideas. The project’s outcomes suggest, given a concrete structure and an invitation to collaborate, drama can be a powerful learning medium for children with ASD. The conclusion reflects on the diverse meaning of inclusive practice which can be achieved within specialist settings.

Cognition in males and females with autism: similarities and differences

The male bias in autism spectrum conditions (ASC) has led to females with ASC being under-researched. This lack of attention to females could hide variability due to sex that may explain some of the heterogeneity within ASC. In this study we investigate four key cognitive domains (mentalizing and emotion perception, executive function, perceptual attention to detail, and motor function) in ASC, to test for similarities and differences between males and females with and without ASC (n = 128 adults; n = 32 per group). In the mentalizing and facial emotion perception domain, males and females with ASC showed similar deficits compared to neurotypical controls. However, in attention to detail and dexterity involving executive function, although males with ASC showed poorer performance relative to neurotypical males, females with ASC performed comparably to neurotypical females. We conclude that performance in the social-cognitive domain is equally impaired in male and female adults with ASC. However, in specific non-social cognitive domains, performance within ASC depends on sex. This suggests that in specific domains, cognitive profiles in ASC are modulated by sex.

Empathy and emotion recognition in people with autism, first-degree relatives, and controls

Empathy is the lens through which we view others' emotion expressions, and respond to them. In this study, empathy and facial emotion recognition were investigated in adults with autism spectrum conditions (ASC; N=314), parents of a child with ASC (N=297) and IQ-matched controls (N=184). Participants completed a self-report measure of empathy (the Empathy Quotient [EQ]) and a modified version of the Karolinska Directed Emotional Faces Task (KDEF) using an online test interface. Results showed that mean scores on the EQ were significantly lower in fathers (p<0.05) but not mothers (p>0.05) of children with ASC compared to controls, whilst both males and females with ASC obtained significantly lower EQ scores (p<0.001) than controls. On the KDEF, statistical analyses revealed poorer overall performance by adults with ASC (p<0.001) compared to the control group. When the 6 distinct basic emotions were analysed separately, the ASC group showed impaired performance across five out of six expressions (happy, sad, angry, afraid and disgusted). Parents of a child with ASC were not significantly worse than controls at recognising any of the basic emotions, after controlling for age and non-verbal IQ (all p>0.05). Finally, results indicated significant differences between males and females with ASC for emotion recognition performance (p<0.05) but not for self-reported empathy (p>0.05). These findings suggest that self-reported empathy deficits in fathers of autistic probands are part of the 'broader autism phenotype'. This study also reports new findings of sex differences amongst people with ASC in emotion recognition, as well as replicating previous work demonstrating empathy difficulties in adults with ASC. The use of empathy measures as quantitative endophenotypes for ASC is discussed.

Subgrouping the autism "spectrum": reflections on DSM-5

DSM-5 has moved autism from the level of subgroups ("apples and oranges") to the prototypical level ("fruit"). But making progress in research, and ultimately improving clinical practice, will require identifying subgroups within the autism spectrum.

Genetic variation in GABRB3 is associated with Asperger syndrome and multiple endophenotypes relevant to autism.

BACKGROUND: Autism spectrum conditions (ASC) are associated with deficits in social interaction and communication, alongside repetitive, restricted, and stereotyped behavior. ASC is highly heritable. The gamma-aminobutyric acid (GABA)-ergic system has been associated consistently with atypicalities in autism, in both genetic association and expression studies. A key component of the GABA-ergic system is encoded by the GABRB3 gene, which has been previously implicated both in ASC and in individual differences in empathy. METHODS: In this study, 45 genotyped single nucleotide polymorphisms (SNPs) within GABRB3 were tested for association with Asperger syndrome (AS), and related quantitative traits measured through the following tests: the Empathy Quotient (EQ), the Autism Spectrum Quotient (AQ), the Systemizing Quotient-Revised (SQ-R), the Embedded Figures Test (EFT), the Reading the Mind in the Eyes Test (RMET), and the Mental Rotation Test (MRT). Two-loci, three-loci, four-loci haplotype analyses, and one seven-loci haplotype analysis were also performed in the AS case--control sample. RESULTS: Three SNPs (rs7180158, rs7165604, rs12593579) were significantly associated with AS, and two SNPs (rs9806546, rs11636966) were significantly associated with EQ. Two SNP-SNP pairs, rs12438141-rs1035751 and rs12438141-rs7179514, showed significant association with variation in the EFT scores. One SNP-SNP pair, rs7174437-rs1863455, was significantly associated with variation in the MRT scores. Additionally, a few haplotypes, including a 19 kb genomic region that formed a linkage disequilibrium (LD) block in our sample and contained several nominally significant SNPs, were found to be significantly associated with AS. CONCLUSION: The current study confirms the role of GABRB3 as an important candidate gene in both ASC and normative variation in related endophenotypes.

Exploring writing in products in students with language impairments and autism spectrum disorders

Oral language skills scaffold written text production; students with oral language difficulties often experience writing problems. The current study examines the ways in which oral language problems experienced by students with language impairment (LI) and students with autism spectrum disorders (ASD) impact on their production of written text. One hundred and fifty seven participants (Mage = 10;2) with LI or ASD completed standardized measures of oral language, transcription, working memory, and nonverbal ability and produced a written narrative text assessed for productivity, grammatical accuracy, and quality. Measures of transcription, productivity, and grammatical accuracy, but not text quality, were poorer for students with LI. Transcription skills accounted for the majority of variance in the writing of the LI cohort. For the ASD cohort, handwriting, oral language and autism symptomatology were significant predictors. When students with ASD also experienced language problems, their performance was equivalent to that observed in the LI cohort.

Disorder-specific functional abnormalities during temporal discounting in youth with Attention Deficit Hyperactivity Disorder (ADHD), Autism and comorbid ADHD and Autism

Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are often comorbid and share cognitive abnormalities in temporal foresight. A key question is whether shared cognitive phenotypes are based on common or different underlying pathophysiologies and whether comorbid patients have additive neurofunctional deficits, resemble one of the disorders or have a different pathophysiology. We compared age- and IQ-matched boys with non-comorbid ADHD (18), non-comorbid ASD (15), comorbid ADHD and ASD (13) and healthy controls (18) using functional magnetic resonance imaging (fMRI) during a temporal discounting task. Only the ASD and the comorbid groups discounted delayed rewards more steeply. The fMRI data showed both shared and disorder-specific abnormalities in the three groups relative to controls in their brain-behaviour associations. The comorbid group showed both unique and more severe brain-discounting associations than controls and the non-comorbid patient groups in temporal discounting areas of ventromedial and lateral prefrontal cortex, ventral striatum and anterior cingulate, suggesting that comorbidity is neither an endophenocopy of the two pure disorders nor an additive pathology.

Abnormal functional activation and maturation of fronto-striato-temporal and cerebellar regions during sustained attention in autism spectrum disorder

Objective Sustained attention problems are common in people with autism spectrum disorder (ASD) and may have significant implications for the diagnosis and management of ASD and associated comorbidities. Furthermore, ASD has been associated with atypical structural brain development. The authors used functional MRI to investigate the functional brain maturation of attention between childhood and adulthood in people with ASD. Method Using a parametrically modulated sustained attention/vigilance task, the authors examined brain activation and its linear correlation with age between childhood and adulthood in 46 healthy male adolescents and adults (ages 11–35 years) with ASD and 44 age- and IQ-matched typically developing comparison subjects. Results Relative to the comparison group, the ASD group had significantly poorer task performance and significantly lower activation in inferior prefrontal cortical, medial prefrontal cortical, striato-thalamic, and lateral cerebellar regions. A conjunction analysis of this analysis with group differences in brain-age correlations showed that the comparison group, but not the ASD group, had significantly progressively increased activation with age in these regions between childhood and adulthood, suggesting abnormal functional brain maturation in ASD. Several regions that showed both abnormal activation and functional maturation were associated with poorer task performance and clinical measures of ASD and inattention. Conclusions The results provide first evidence that abnormalities in sustained attention networks in individuals with ASD are associated with underlying abnormalities in the functional brain maturation of these networks between late childhood and adulthood.

The neuropsychology of male adults with High-Functioning Autism or Asperger Syndrome

Autism Spectrum Disorder (ASD) is diagnosed on the basis of behavioral symptoms, but cognitive abilities may also be useful in characterizing individuals with ASD. One hundred seventy-eight high-functioning male adults, half with ASD and half without, completed tasks assessing IQ, a broad range of cognitive skills, and autistic and comorbid symptomatology. The aims of the study were, first, to determine whether significant differences existed between cases and controls on cognitive tasks, and whether cognitive profiles, derived using a multivariate classification method with data from multiple cognitive tasks, could distinguish between the two groups. Second, to establish whether cognitive skill level was correlated with degree of autistic symptom severity, and third, whether cognitive skill level was correlated with degree of comorbid psychopathology. Fourth, cognitive characteristics of individuals with Asperger Syndrome (AS) and high-functioning autism (HFA) were compared. After controlling for IQ, ASD and control groups scored significantly differently on tasks of social cognition, motor performance, and executive function (P's < 0.05). To investigate cognitive profiles, 12 variables were entered into a support vector machine (SVM), which achieved good classification accuracy (81%) at a level significantly better than chance (P < 0.0001). After correcting for multiple correlations, there were no significant associations between cognitive performance and severity of either autistic or comorbid symptomatology. There were no significant differences between AS and HFA groups on the cognitive tasks. Cognitive classification models could be a useful aid to the diagnostic process when used in conjunction with other data sources-including clinical history.

Elevated fetal steroidogenic activity in autism

Autism affects males more than females, giving rise to the idea that the influence of steroid hormones on early fetal brain development may be one important early biological risk factor. Utilizing the Danish Historic Birth Cohort and Danish Psychiatric Central Register, we identified all amniotic fluid samples of males born between 1993 and 1999 who later received ICD-10 (International Classification of Diseases, 10th Revision) diagnoses of autism, Asperger syndrome or PDD-NOS (pervasive developmental disorder not otherwise specified) (n=128) compared with matched typically developing controls. Concentration levels of Δ4 sex steroids (progesterone, 17α-hydroxy-progesterone, androstenedione and testosterone) and cortisol were measured with liquid chromatography tandem mass spectrometry. All hormones were positively associated with each other and principal component analysis confirmed that one generalized latent steroidogenic factor was driving much of the variation in the data. The autism group showed elevations across all hormones on this latent generalized steroidogenic factor (Cohen's d=0.37, P=0.0009) and this elevation was uniform across ICD-10 diagnostic label. These results provide the first direct evidence of elevated fetal steroidogenic activity in autism. Such elevations may be important as epigenetic fetal programming mechanisms and may interact with other important pathophysiological factors in autism.

A genome wide association study of mathematical ability reveals an association at chromosome 3q29, a locus associated with autism and learning difficulties: a preliminary study

Mathematical ability is heritable, but few studies have directly investigated its molecular genetic basis. Here we aimed to identify specific genetic contributions to variation in mathematical ability. We carried out a genome wide association scan using pooled DNA in two groups of U.K. samples, based on end of secondary/high school national academic exam achievement: high (n = 419) versus low (n = 183) mathematical ability while controlling for their verbal ability. Significant differences in allele frequencies between these groups were searched for in 906,600 SNPs using the Affymetrix GeneChip Human Mapping version 6.0 array. After meeting a threshold of p<1.5×10-5, 12 SNPs from the pooled association analysis were individually genotyped in 542 of the participants and analyzed to validate the initial associations (lowest p-value 1.14 ×10-6). In this analysis, one of the SNPs (rs789859) showed significant association after Bonferroni correction, and four (rs10873824, rs4144887, rs12130910 rs2809115) were nominally significant (lowest p-value 3.278 × 10-4). Three of the SNPs of interest are located within, or near to, known genes (FAM43A, SFT2D1, C14orf64). The SNP that showed the strongest association, rs789859, is located in a region on chromosome 3q29 that has been previously linked to learning difficulties and autism. rs789859 lies 1.3 kbp downstream of LSG1, and 700 bp upstream of FAM43A, mapping within the potential promoter/regulatory region of the latter. To our knowledge, this is only the second study to investigate the association of genetic variants with mathematical ability, and it highlights a number of interesting markers for future study.