Emotional language processing in autism spectrum disorders: a systematic review.

Autism spectrum disorder (ASD) is frequently associated with communicative impairment, regardless of intelligence level or mental age. Impairment of prosodic processing in particular is a common feature of ASD. Despite extensive overlap in neural resources involved in prosody and music processing, music perception seems to be spared in this population. The present study is the first to investigate prosodic phrasing in ASD in both language and music, combining event-related brain potential (ERP) and behavioral methods. We tested phrase boundary processing in language and music in neuro-typical adults and high-functioning individuals with ASD. We targeted an ERP response associated with phrase boundary processing in both language and music – i.e., the Closure Positive Shift (CPS). While a language-CPS was observed in the neuro-typical group, for ASD participants a smaller response failed to reach statistical significance. In music, we found a boundary-onset music-CPS for both groups during pauses between musical phrases. Our results support the view of preserved processing of musical cues in ASD individuals, with a corresponding prosodic impairment. This suggests that, despite the existence of a domain-general processing mechanism (the CPS), key differences in the integration of features of language and music may lead to the prosodic impairment in ASD.

Motor impairments in neurodevelopmental disorders, specifically autism spectrum disorder (ASD), are prevalent and pervasive. Moreover, motor impairments may be the first sign of atypical development in ASD and likely contribute to abnormalities in social communication. However, measurement of motor function in ASD has lagged behind other behavioral phenotyping. Quantitative and neurodiagnostic measures of motor function can help identify specific motor impairments in ASD and the underlying neural mechanisms that might be implicated. These findings can serve as markers of early diagnosis, clinical stratification, and treatment targets. Here, we briefly review recent studies on the importance of motor function to other developmental domains in ASD. We then highlight studies that have applied quantitative and neurodiagnostic measures to better measure motor impairments in ASD and the neural mechanisms that may contribute to these abnormalities. Information from advanced quantitative and neurodiagnostic methods of motor function contribute to a better understanding of the specific and subtle motor impairments in ASD, and the relationship of motor function to language and social development. Greater utilization of these methods can assist with early diagnosis and development of targeted interventions. However, there remains a need to utilize these approaches in children with neurodevelopmental disorders across a developmental trajectory and with varying levels of cognitive function.

Individuals with autism spectrum disorder (ASD) have difficulties in understanding emotional language, but little research has discussed the developmental course of the processing of emotional words in the clinical population. Previous studies have revealed distinct processing for emotion-label (e.g., happiness) and emotion-laden (e.g., birthday) words in typically developing (TD) children and adolescents. Extending these findings, the study used event-related potentials (ERPs) to explore the processing of these two types of emotional words in children and adolescents with ASD. The stimuli included two-character Chinese words with factors of word type (emotion-label versus emotion-laden) and valence (positive versus negative). The participants were 11 to 14-year-old children and adolescents with ASD (N = 23) and age-matched TD peers (N = 23). They categorized emotion valence for words while their brain responses were recorded. Both the TD and the ASD groups exhibited emotional processing for all emotional words across the N400 and late positivity component (LPC). The emotional processing was modulated by word type but varied with group and valence. A trend for group differences was observed in processing positive words at 500-600ms. In particular, the emotion effects of positive emotion-label words were positively correlated with social dysfunction across all participants. These findings suggested that children and adolescents with ASD have a selective impairment in understanding emotional concepts from language. The ERP measurements may reflect atypical emotional word processing for individuals with higher autistic severity in positive valence contexts.

Autism spectrum disorders (ASD) are characterized by executive dysfunction, and working memory (WM) comprises one core component of executive function. Many studies have investigated WM impairments in individuals with ASD, however, a conclusive agreement has not been reached. The present study provided a meta-analytic review of WM impairments in individuals with ASD and evaluated potential moderating variables of this problem. Twenty-eight studies were included in this study, and the participants comprised 819 individuals with ASD and 875 healthy controls. A significant WM impairment (Cohen's d = -0.61) was identified in the individuals with ASD, however, this impairment was not associated with age. Results of moderation analyses showed that (a) spatial WM was more severely impaired than verbal WM and (b) the component of cognitive processing (maintenance vs. maintenance plus manipulation) did not affect the severity of WM impairments. These findings suggest that WM is impaired in individuals with ASD and may have implications for interventions related to WM impairments in these individuals.

Through the eyes of autism: Eye care for these special patients

Reduced preference for smooth over rough surfaces in autism spectrum disorder

Failure of the amygdala to habituate, or decrease response intensity, to repeatedly presented faces may be one mechanism by which individuals with autism spectrum disorders (ASD) develop and maintain social symptoms. However, genetic influences on habituation in ASD have not been examined. We hypothesized that serotonin transporter-linked promoter region (5-HTTLPR) genotype affects change in amygdala response to repeated sad faces differently in individuals with ASD vs healthy controls. Forty-four youth with ASD and 65 controls aged 8-19 years were genotyped and underwent an event-related functional magnetic resonance imaging scan where they identified the gender of emotional faces presented for 250 ms. The first half of the run was compared with the second half to assess habituation. 5-HTTLPR genotype influences amygdala habituation to sad faces differently for individuals with ASD vs controls. The genotype-by-diagnosis-by-run half interaction was driven by individuals with ASD and low expressing genotypes (S/S, S/L(G) and L(G)/L(G)), who trended toward sensitization (increase in amygdala activation) and whose habituation scores significantly differed from individuals with ASD and higher expressing genotypes (L(A)/L(A), S/L(A) and L(A)/L(G)) as well as controls with low expressing genotypes. Our results show that amygdala response to social stimuli in ASD, which may contribute to social symptoms, is genetically influenced.

Abnormal auditory neuromagnetic M50 and M100 responses, reflecting primary/secondary auditory cortex processing, have been reported in children who have autism spectrum disorder (ASD). Some studies have reported an association between delays in these responses and language impairment. However, as most prior research has focused on verbal individuals with ASD without cognitive impairment, rather little is known about neural activity during auditory processing in minimally verbal or nonverbal children who have ASD (ASD-MVNV)—children with little or no speech and often significant cognitive impairment. To understand the neurophysiological mechanisms underlying auditory processing in ASD-MVNV children, magnetoencephalography (MEG) measured M50 and M100 responses arising from left and right superior temporal gyri during tone stimuli in three cohorts: (1) MVNV children who have ASD (ASD-MVNV), (2) verbal children who have ASD and no intellectual disability (ASD-V), and (3) typically developing (TD) children. One hundred and five participants (8–12 years) were included in the final analyses (ASD-MVNV: n = 16, 9.85 ± 1.32 years; ASD-V: n = 55, 10.64 ± 1.31 years; TD: n = 34, 10.18 ± 1.36 years). ASD-MVNV children showed significantly delayed M50 and M100 latencies compared to TD. These delays tended to be greater than the corresponding delays in verbal children with ASD. Across cohorts, delayed latencies were associated with language and communication skills, assessed by the Vineland Adaptive Behavior Scale Communication Domain. Findings suggest that auditory cortex neural activity measures could be dimensional objective indices of language impairment in ASD for either diagnostic (e.g., via threshold or cutoff) or prognostic (considering the continuous variable) use.

Objectives: 
\nThere has been a significant increase in the incidence rates and public awareness of autism spectrum disorder (ASD) in recent years. The DSM-5’s latest modification of diagnostic criteria for ASD has also stimulated considerable debate. Despite the rising concerns, few studies have been conducted in the Chinese population of Hong Kong, especially among youth and adolescents. This study investigates the clinical profile of ASD in adolescents in Hong Kong. In addition to using screening instruments commonly used to assess specific ASD characteristics, other psychometric measures for internalizing and externalizing problems are employed to examine their associations with the ASD symptoms. It also assesses the extent to which different ASD symptoms and their associated features predict parenting stress.
\nMethods:
\nA total of 143 adolescents aged between 11 and 17 (M = 14.17; SD = 1.76) completed this study with their parents, including 71 adolescents with ASD and 72 typically developing adolescents. Adolescents completed two self-report measures of emotional symptoms: the Spence Children’s Anxiety Scale (SCAS) and Children’s Depression Inventory (CDI). Their parents completed the Autism Spectrum Screening Questionnaire (ASSQ), Child Behaviour Checklist (CBCL), and Spence Children’s Anxiety Scale – Parent version (SCAS-P) for evaluating their child’s characteristics. Parents also completed the Depression, Anxiety, and Stress Scale-21 (DASS-21) and Parenting Stress Index-Short Form (PSI-SF) for measuring their own parenting stress.
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\nResults:
\nAll measures showed good to excellent internal consistency. They were as reliable and internally consistent as the original English versions. Parent reports in the ASD group were significantly higher than in the control group on all measures. Mean ASSQ scores in the ASD group fell within the clinical range. Optimal ASSQ cutoff scores were estimated using receiver operating characteristics analysis. ASD symptoms, as well as internalizing and externalizing problems, were found to be significant discriminators between the ASD group and the controls. In addition, parents reported that their child’s emotional and behaviour problems were more distressing than the ASD symptoms.
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\nDiscussion:
\nThis study highlights the importance of evaluating specific ASD characteristics and their associated symptoms of emotional and behavioural disturbances. This study suggests an optimal cutoff score of 9 for the ASSQ in Hong Kong. However, there is a need to assess its generalizability using large-scale community samples and other childhood clinical conditions. Although the findings appear to support the revised DSM-5 taxonomy of ASD, they must be interpreted with caution. Future treatments should provide parents with adequate professional support for reducing parenting stress and helping them cope with their child’s social, emotional, and behavioural impairments. 
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\nConclusions:
\nThis study documents preliminary norms for a broad range of measures for adolescents with ASD in Hong Kong. It also provides a useful empirical basis for future investigations of the interplay between specific ASD characteristics and their associated features. Regarding treatment planning, this study postulates a comprehensive treatment model for adolescents with ASD to guide treatment research.

Recent studies have revealed that atypical sensory perception is common in individuals with autism spectrum disorder (ASD) and is considered a potential cause of social difficulties. Self-reports by individuals with ASD have provided great insights into atypical perception from the first-person point of view and indicated its dependence on the environment. This study aimed to investigate the patterns and environmental causes of atypical auditory perception in individuals with ASD. Qualitative data from subject reports are inappropriate for statistical analysis, and reporting subjective sensory experiences is not easy for every individual. To cope with such challenges, we employed audio signal processing methods to simulate the potential patterns of atypical auditory perception. The participants in our experiment were able to select and adjust the strength of the processing methods to manipulate the sounds in the videos to match their experiences. Thus, the strength of atypical perception was recorded quantitatively and then analyzed to assess its correlation with the audio-visual stimuli contained in the videos the participants observed. In total, 22 participants with ASD and 22 typically developed (TD) participants were recruited for the experiment. The results revealed several common patterns of atypical auditory perception: Louder sounds perceived in a quiet environment, noise perception induced by intense and unsteady audio-visual stimuli, and echo perception correlated with movement and variation in sound level. The ASD group reported atypical perceptions more frequently than the control group. However, similar environmental causes were shared by the ASD and TD groups. The results help us infer the potential neural and physiological mechanisms of sensory processing in ASD.

Anxiety disorders are common in autism spectrum disorder (ASD) and associated with social-communication impairment and repetitive behavior symptoms. The neurobiology of anxiety in ASD is unknown, but amygdala dysfunction has been implicated in both ASD and anxiety disorders. Using resting-state functional magnetic resonance imaging, we compared amygdala-prefrontal and amygdala-striatal connections across three demographically matched groups studied in the Autism Brain Imaging Data Exchange (ABIDE): ASD with a comorbid anxiety disorder (N = 25; ASD + Anxiety), ASD without a comorbid disorder (N = 68; ASD-NoAnx), and typically developing controls (N = 139; TD). Relative to ASD-NoAnx and TD controls, ASD + Anxiety individuals had decreased connectivity between the amygdala and dorsal/rostral anterior cingulate cortex (dACC/rACC). The functional connectivity of these connections was not affected in ASD-NoAnx, and amygdala connectivity with ventral ACC/medial prefrontal cortex (mPFC) circuits was not different in ASD + Anxiety or ASD-NoAnx relative to TD. Decreased amygdala-dorsomedial prefrontal cortex (dmPFC)/rACC connectivity was associated with more severe social impairment in ASD + Anxiety; amygdala-striatal connectivity was associated with restricted, repetitive behavior (RRB) symptom severity in ASD-NoAnx individuals. These findings suggest comorbid anxiety in ASD is associated with disrupted emotion-monitoring processes supported by amygdala-dACC/mPFC pathways, whereas emotion regulation systems involving amygdala-ventromedial prefrontal cortex (vmPFC) are relatively spared. Our results highlight the importance of accounting for comorbid anxiety for parsing ASD neurobiological heterogeneity.

Research on attention allocation to social and non-social stimuli in autism spectrum disorder (ASD) has produced mixed results, with some studies suggesting that attention allocation is atypical in ASD (e.g., Klin, Jones, Schultz, Vokmar, & Cohen, 2002) and others finding no significant differences in attention allocation patterns when comparing individuals with ASD to typically developing (TD) controls (e.g., Parish-Morris et al. 2013). This meta-analysis aggregates results from 68 articles that compared individuals with ASD with TD controls, using eye-tracking measures of attention. As an index of attention allocation, mean effect sizes for looking time to six areas of interest (AOIs) are computed in this meta-analysis: eyes, mouth, face, body, non-social elements, and the whole screen. The results suggest the presence of atypical attention allocation in ASD, indicated by small but significant effect sizes: overall reduced attention to the eyes (d = 0.33), mouth (d = 0.25), and face (d = 0.4); increased attention to the body (d = −0.48) and non-social elements (d = −0.34); and reduced attention to the screen (d = 0.53). This pattern of findings suggests less accessing of social information by individuals with ASD. The results are discussed in light of future research directions.

An increasing body of evidence supports the role of altered sensory processing in autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). This exploratory study undertook corneal confocal microscopy (CCM) to assess for differences in corneal nerve fiber density (CNFD), branch density (CNBD) and fiber length (CNFL) in relation to ASD severity in children with ASD+ADHD (n = 21), ASD (n = 6) and healthy controls (HC) (n = 15). CNBD was significantly lower in children with ASD+ADHD (P = 0.002) and ASD (P < 0.001) and CNFL was significantly lower in children with ASD (P = 0.02) compared to HC. However, CNFD (mean difference = 2.28, 95% CI [-5.84, 10.40], P > 0.99) CNBD (mean difference = 14.1, 95% CI [-8.22, 36.4], p = 0.37) and CNFL (mean difference = 2.46, 95% CI [-2.28, 7.20], p = 0.61) did not differ between ASD+ADHD and ASD. CNFD (P = 0.876), CNBD (P = 0.405) and CNFL (P = 0.606) did not correlate with the severity of ASD. Corneal confocal microscopy reveals sensory nerve degeneration in children with ASD+ADHD and ASD alone compared to controls. Larger studies integrating CCM with sensory and cognitive assessment are required to determine the utility of CCM as a clinical screening strategy for neurodegneration in ASD, ADHD and ASD-ADHD combined.

Language impairments, a hallmark feature of autism spectrum disorders (ASD), have been related to neuroanatomical and functional abnormalities. Abnormal lateralization of the functional language network, increased reliance on visual processing areas, and increased posterior brain activation have all been reported in ASD and proposed as explanatory models of language difficulties. Nevertheless, inconsistent findings across studies have prevented a comprehensive characterization of the functional language network in ASD. The aim of this study was to quantify common and consistent patterns of brain activation during language processing in ASD and typically developing control (TD) participants using a meta-analytic approach. Activation likelihood estimation (ALE) meta-analysis was used to examine 22 previously published functional Magnetic Resonance Imaging (fMRI)/positron emission tomography studies of language processing (ASD: N = 328; TD: N = 324). Tasks included in this study addressed semantic processing, sentence comprehension, processing figurative language, and speech production. Within-group analysis showed largely overlapping patterns of language-related activation in ASD and TD groups. However, the ASD participants, relative to TD participants, showed: (1) more right hemisphere activity in core language areas (i.e., superior temporal gyrus and inferior frontal gyrus), particularly in tasks where they had poorer performance accuracy; (2) bilateral MTG hypo-activation across many different paradigms; and (3) increased activation of the left lingual gyrus in tasks where they had intact performance. These findings show that the hypotheses reviewed here address the neural and cognitive aspects of language difficulties in ASD across all tasks only in a limited way. Instead, our findings suggest the nuances of language and brain in ASD in terms of its context-dependency. Autism Res 2016, 9: 1046-1057. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Motor impairments in autism spectrum disorders (ASD) have received far less research attention than core social-communication and cognitive features. Yet, behavioral, neurophysiological, neuroimaging and histopathological studies have documented abnormal motor system development in the majority of individuals with ASD suggesting that these deficits may be primary to the disorder. There are several unique advantages to studying motor development in ASD. First, the neurophysiological substrates of motor skills have been well-characterized via animal and human lesion studies. Second, many of the single-gene disorders associated with ASD also are characterized by motor dysfunctions. Third, recent evidence suggests that the onset of motor dysfunctions may precede the emergence of social and communication deficits during the first year of life in ASD. Motor deficits documented in ASD indicate disruptions throughout the neuroaxis affecting cortex, striatum, the cerebellum and brainstem. Questions remain regarding the timing and development of motor system alterations in ASD, their association with defining clinical features, and their potential for parsing heterogeneity in ASD. Pursuing these questions through neurobiologically informed translational research holds great promise for identifying gene-brain pathways associated with ASD.