Language and music phrase boundary processing in Autism Spectrum Disorder: An ERP study

In his first description of Autism Spectrum Disorders (ASD), Kanner emphasized emotional impairments by characterizing children with ASD as indifferent to other people, self-absorbed, emotionally cold, distanced, and retracted. Thereafter, emotional impairments became regarded as part of the social impairments of ASD, and research mostly focused on understanding how individuals with ASD recognize visual expressions of emotions from faces and body postures. However, it still remains unclear how emotions are processed outside of the visual domain. This systematic review aims to fill this gap by focusing on impairments of emotional language processing in ASD. We systematically searched PubMed for papers published between 1990 and 2013 using standardized search terms. Studies show that people with ASD are able to correctly classify emotional language stimuli as emotionally positive or negative. However, processing of emotional language stimuli in ASD is associated with atypical patterns of attention and memory performance, as well as abnormal physiological and neural activity. Particularly, younger children with ASD have difficulties in acquiring and developing emotional concepts, and avoid using these in discourse. These emotional language impairments were not consistently associated with age, IQ, or level of development of language skills. We discuss how emotional language impairments fit with existing cognitive theories of ASD, such as central coherence, executive dysfunction, and weak Theory of Mind. We conclude that emotional impairments in ASD may be broader than just a mere consequence of social impairments, and should receive more attention in future research.

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.

Autism spectrum disorders (ASD) are pervasive neurodevelopmental disorders entailing social and cognitive deficits, including marked problems with language. Numerous genes have been associated with ASD, but it is unclear how language deficits arise from gene mutation or dysregulation. It is also unclear why ASD shows such high prevalence within human populations. Interestingly, the emergence of a modern faculty of language has been hypothesized to be linked to changes in the human brain/skull, but also to the process of self-domestication of the human species. It is our intention to show that people with ASD exhibit less marked domesticated traits at the morphological, physiological, and behavioral levels. We also discuss many ASD candidates represented among the genes known to be involved in the “domestication syndrome” (the constellation of traits exhibited by domesticated mammals, which seemingly results from the hypofunction of the neural crest) and among the set of genes involved in language function closely connected to them. Moreover, many of these genes show altered expression profiles in the brain of autists. In addition, some candidates for domestication and language-readiness show the same expression profile in people with ASD and chimps in different brain areas involved in language processing. Similarities regarding the brain oscillatory behavior of these areas can be expected too. We conclude that ASD may represent an abnormal ontogenetic itinerary for the human faculty of language resulting in part from changes in genes important for the “domestication syndrome” and, ultimately, from the normal functioning of the neural crest.

Numerous studies have revealed atypical face processing in autism spectrum disorders (ASD) characterized by social interaction and communication difficulties. This study investigated sensitivity to face-likeness in ASD. In Experiment 1, we found a strong positive correlation between the face-likeness ratings of non-face objects in the ASD (11–19 years old) and the typically developing (TD) group (9–21 years old). In Experiment 2 (the scalp-recorded event-related potential experiment), the participants of both groups (ASD, 12–19 years old; TD, 12–18 years old) exhibited an enhanced face-sensitive N170 amplitude to a face-like object. Whereas the TD adolescents showed an enhanced N170 during the face-likeness judgements, adolescents with ASD did not. Thus, both individuals with ASD and TD individuals have a perceptual and neural sensitivity to face-like features in objects. When required to process face-like features, a face-related brain system reacts more strongly in TD individuals but not in individuals with ASD.

Atypical lexicosemantic function of extrastriate cortex in autism spectrum disorder: Evidence from functional and effective connectivity

The perception ability has attained much recognition in the identification of cognitive processing and decision-making in autism spectrum disorder (ASD) individuals. However, the prior studies have subjectively worked on perception ability using conditioning paradigms that can be intolerable for ASD individuals. The present paper quantitatively investigates the perception ability of ASD individuals by modelling visual judgement and statistical learning. Thirty ASD and typically developing (TD) individuals are selected for experimenting distinguishing animated images related to risk situations with different risk levels. The experimental paradigm-based behavioural measures (reaction time, d′ index, and accuracy) revealed that ASD individuals, although performed poorly than TDs, they visually and statistically perceived the risk. Quantitatively, the perception level in ASD is (mean 0.57 ± 0.02) in the range [0 1]. In comparison to TDs, the attenuated visual and statistical learning during the experiment could lead to impaired perception in ASD. However, when statistical learning comes into action (comparing performance in block 1 and block 6), it played a crucial role in improving visual knowledge; thus, the perception ability of ASD individuals. In the future, the studies can implicate the quantitative perception to identify other deficits in the ASD phenotype.

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 altered gut microbiota, which appears to regulate ASD symptoms via gut microbiota-brain interactions. Rapid assessment of gut microbiota profiles in ASD individuals in varying physiological contexts is important to understanding the role of the microbiota in regulating ASD symptoms. Microbiomes secrete extracellular membrane vesicles (EVs) to communicate with host cells and secreted EVs are widely distributed throughout the body including the blood and urine. In the present study, we investigated whether bacteria-derived EVs in urine are useful for the metagenome analysis of microbiota in ASD individuals. To address this, bacterial DNA was isolated from bacteria-derived EVs in the urine of ASD individuals. Subsequent metagenome analysis indicated markedly altered microbiota profiles at the levels of the phylum, class, order, family, and genus in ASD individuals relative to control subjects. Microbiota identified from urine EVs included gut microbiota reported in previous studies and their up- and down-regulation in ASD individuals were partially consistent with microbiota profiles previously assessed from ASD fecal samples. However, overall microbiota profiles identified in the present study represented a distinctive microbiota landscape for ASD. Particularly, the occupancy of g_Pseudomonas, g_Sphingomonas, g_Agrobacterium, g_Achromobacter, and g_Roseateles decreased in ASD, whereas g_Streptococcus, g_Akkermansia, g_Rhodococcus, and g_Halomonas increased. These results demonstrate distinctively altered gut microbiota profiles in ASD, and validate the utilization of urine EVs for the rapid assessment of microbiota in ASD.

Autism spectrum disorder (ASD) is a developmental disability that is poorly understood. ASD can influence communication, social interaction, and behavior. Children with ASD often have sensory hypersensitivities, including auditory hypersensitivity (hyperacusis). In adults with hyperacusis who are otherwise neurotypical, the medial olivocochlear (MOC) efferent reflex is stronger than usual. In children with ASD, the MOC reflex has been measured, but without also assessing hyperacusis. We assessed the MOC reflex in children with ASD by measuring the strength of MOC-induced inhibition of transient-evoked otoacoustic emissions (TEOAEs), a noninvasive physiological measure that reflects cochlear amplification. MOC activity was evoked by contralateral noise. Hyperacusis was assessed subjectively on the basis of the children's symptoms. We found a significant correlation between hyperacusis scores and MOC strength in children with ASD. When children were divided into ASD-with-severe-hyperacusis (ASDs), ASD-with-not-severe-hyperacusis (ASDns), and neurotypical (NT) groups, the last two groups had similar hyperacusis and MOC reflexes, whereas the ASDs group, on average, had hyperacusis and MOC reflexes that were approximately twice as strong. The MOC inhibition of TEOAEs averaged larger at all frequencies in the ASDs compared with ASDns and NT groups. The results suggest that the MOC reflex can be used to estimate hyperacusis in children with ASD and might be used to validate future questionnaires to assess hyperacusis. Our results also provide evidence that strong MOC reflexes in children with ASD are associated with hyperacusis and that hyperacusis is a comorbid condition and is not a necessary, integral part of the abnormal neural processing associated with ASD.NEW & NOTEWORTHY Children with autism spectrum disorder (ASD) are a heterogeneous group, some with hyperacusis and some without. Our research shows that hyperacusis can be estimated in children with ASD by using medial olivocochlear (MOC) reflex measurements. By establishing that an objective measure correlates with attributes of hyperacusis, our results enable future work to enable subtyping of children with ASD to provide improved individualized treatments to at-risk children and those without adequate language to describe their hyperacusis symptoms.

Objective: The present study explores the co-occurrence of autism spectrum disorder (ASD) with associated disorders such as epilepsy, attention deficit hyperactive disorder (ADHD), Down’s syndrome (DS), and cerebral palsy (CP).
 Methods: This cross-sectional study was carried out in special schools of four districts in Karnataka. A total of 49 ASD individuals were identified among 552 developmentally challenged children. ASD individuals were screened for associated neurological disorders and segregated the data as ASD, ASD with epilepsy, ASD-epilepsy-ADHD, ASD with DS, and ASD with CP. The karyotype analysis was carried out for chromosomal anomalies.
 Results: It is found that 57% of the individuals showed only ASD features and the remaining 43% shared ASD features with other neurological disorders. Among 43% of comorbidity, 35% of ASD individuals have epilepsy, 2% have epilepsy-ADHD, 4% have DS, and 2% have CP.
 Conclusion: This study supports the strong association between ASD with epilepsy, DS, ADHD, and CP. However, the extent of association of ASD with epilepsy is higher than other neurological disorders. As both are complex neurological disorders, they both show intellectual disability and involve multiple genetic factors. The present investigation is the unique and first report of this study region and also supports earlier studies, suggesting that there is an association of ASD with other neurological disorders.

IntroductionVerbal fluency, a cognitive function that reflects executive functions and the rapid retrieval of pertinent information from memory, has yielded inconsistent findings in previous research on autism spectrum disorder (ASD), however in schizophrenia (SCH) semantic fluency exhibits a more pronounced impairment compared to letter fluency.ObjectivesIn this study we aim to comprehensively investigate verbal fluency in ASD, SCH, and neurotypical healthy control individuals (NTP). The primary objective is to investigate disparities in novel response generation, specifically between the ASD, SCH and NTP groups, using phonemic and semantic fluency tasks. Three central inquiries guide our research: (1) whether differences between groups (ASD, SCH, and NTP) can be identified in word productivity, clustering, errors, and perseverations; (2) whether participants with ASD and SCH exhibit different word production with elevated imageability and concreteness values; and (3) if individuals with ASD and schizophrenia demonstrate reduced productivity during the earlier phases of fluency tasks.MethodsForty participants with ASD (12 female, 24 male, 4 other, mean age: 30.5), 39 with SCH (10 female, 28 male, 1 other, mean age: 34.7) and 41 NTP (13 female, 28 male, mean age: 31.0) were recruited from the outpatient units of the Department of Psychiatry and Psychotherapy, Semmelweis University. Participants were requested to list as many words as they could on two phonemic and two semantic category conditions. Audio recordings were later transcribed. To assess concreteness and imageability, we employed a seven-point scale and recruited independent external raters to evaluate a total of 1481 words.ResultsPreliminary results indicate that the three study groups did not differ significantly in phonemic fluency (F(2, 119)= 0.983, p=0.377), during either time period. However, a significant difference was observed in semantic fluency (F(2, 119)= 6.531, p=0.002). Post-hoc tests (Tukey corrected) revealed that this difference stemmed from impaired performance in the SCH group. Participants with schizophrenia (SCH) exhibited reduced semantic word productivity compared to both neurotypical (NTP) individuals and participants with ASD (Figure 1). However, there were no significant differences between participants with ASD and NTP individuals.Image:ConclusionsIn conclusion, our study investigated the characteristics of verbal fluency in a transdiagnostic approach. While phonemic fluency did not reveal significant differences among the three groups, our analysis of semantic fluency unveiled a distinction. Specifically, individuals with schizophrenia exhibited impaired semantic word productivity. Our study highlights the complex nature of verbal fluency impairments in different conditions and the importance of considering more nuanced methods when assessing cognitive functions.Disclosure of InterestNone Declared

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

Background: Psychotic disorders are characterized by impairment in social cognitive processing, which is associated with poorer community functioning. However, the neural mechanisms of social impairment in psychosis remain unclear. Social impairment is a hallmark of other psychiatric illnesses as well, including autism spectrum disorders (ASD), and the nature and degree of social cognitive impairments across psychotic disorders and ASD are similar, suggesting that mechanisms that are known to underpin social impairments in ASD may also play a role in the impairments seen in psychosis. Specifically, in both humans and animal models of ASD, a cerebellar–parietal network has been identified that is directly related to social cognition and social functioning. In this study we examined social cognition and resting-state brain connectivity in people with psychosis and in neurotypical adults. We hypothesized that social cognition would be most strongly associated with cerebellar–parietal connectivity, even when using a whole-brain data driven approach.Methods: We examined associations between brain connectivity and social cognition in a trans-diagnostic sample of people with psychosis (n = 81) and neurotypical controls (n = 45). Social cognition was assessed using the social cognition domain score of the MATRICS Consensus Cognitive Battery. We used a multivariate pattern analysis to correlate social cognition with resting-state functional connectivity at the individual voxel level.Results: This approach identified a circuit between right cerebellar Crus I, II and left parietal cortex as the strongest correlate of social cognitive performance. This connectivity-cognition result was observed in both people with psychotic disorders and in neurotypical adults.Conclusions: Using a data-driven whole brain approach we identified a cerebellar–parietal circuit that was robustly associated with social cognitive ability, consistent with findings from people with ASD and animal models. These findings suggest that this circuit may be marker of social cognitive impairment trans-diagnostically and support cerebellar–parietal connectivity as a potential therapeutic target for enhancing social cognition.

The ability to coordinate attention to events or objects between interactive social partners, referred to as social attention, is of great significance for adaptive social behaviors and nonverbal communications in our daily life, helping us to infer other person’s inner state (e.g., intentions, goals) and learn about where important events (e.g., food, danger) occur in the environment. In recent years, many studies have demonstrated that social cues (e.g., eye gaze, head orientation and walking direction of biological motion) can trigger reflexive attentional orienting effects using adapted central cueing paradigm originally designed by Posner. However, not all of us are equally adept at directing attention to where others are focusing on, and this ability is strongly impaired in individuals with autism spectrum disorder (ASD), a highly genetic neurodevelopmental disorder marked by striking social deficits and repetitive behaviors. Here we systematically reviewed recent work on abnormal social attention behaviors and its underlying neural mechanisms in ASD. We first expatiated a typical social attention behaviors indexed by covert and overt attention in ASD. It has been documented that ASD individuals tend to show reduced reflexive orienting effect manifesting itself in both covert attention and overt eye movement compared to typically developing individuals (TD). Yet some controversies concerning the malfunction of social attention in ASD remain to be resolved, based on some evidence demonstrating comparable orienting effect between ASD and TD group. Then we summarized the development course of social attention in ASD. Crucially, atypical orienting to eye gaze is more likely to be observed in younger children but not older children or adults with ASD. It is reasonable to postulate that ASD individuals may acquire this ability through overlearning the association between social cues and targets in everyday life as they grow older. Furthermore, we discussed the neural basis of abnormal social attention behaviors in ASD. Using a combination of psychophysical paradigms and neuroimaging techniques, researchers have reported atypical neural activities in superior temporal gyrus and prefrontal cortex under the supraliminal condition as well as abnormal activation in amygdala under the subliminal condition in the brain of ASD. Moreover, the ASD group showed much less difference in activation of frontoparietal attention networks between social and nonsocial attention task than the TD group, implying disruptive social attention in ASD. Finally, several perspectives on further investigations were put forward given the controversies and insufficient evidence concerning the malfunction of social attention in ASD. Future studies should employ multiple types of social cues (e.g., eye gaze and walking direction of biological motion) in conjunction with more ecological paradigms to investigate conscious and non-conscious social attention behaviors from a developmental approach. More importantly, more neuroimaging studies are needed to explore the functional connections among several key cortical regions and subcortical regions underlying atypical social attention behaviors in ASD. Such efforts will help to facilitate the early diagnosis and intervention of ASD.

The intersection of autism spectrum disorder and intellectual disability