Autism Spectrum Disorder Impairment Research Articles

Contributions of filtering and attentional allocation to working memory performance in individuals with autism spectrum disorder.

Past findings on working memory (WM) ability in individuals with autism spectrum disorder (ASD) are mixed. The present objective was to assess not only the integrity of WM capacity, but also the potential contribution of filtering ability and attentional selection to WM performance, in individuals with ASD. A sample of 24 participants with ASD (Mage = 19.6 years) and 24 typically developing participants without ASD (Mage = 20.3 years) participated. Participants completed a computerized paradigm designed to systematically assess WM capacity, visual filtering ability, and attentional selection. In brief, participants were shown visual arrays consisting of 2-8 colored stimuli (circles and/or squares). After a short delay, memory for one of the stimuli was probed. Importantly, participants were informed beforehand that one of the shape types (e.g., circles) was more likely to be probed compared to the other shape type (e.g., squares) - thus making it strategically advantageous to focus on the high frequency shapes and to filter/ignore the low frequency shapes. Eye tracking data were simultaneously collected. The ASD group demonstrated intact WM capacity and filtering ability, but disrupted ability to efficiently allocate capacity under the demands of high WM load. Analysis of eye tracking data suggests the groups may have differed in their strategic approach to encoding stimuli which may have, in turn, contributed to the aforementioned impairment. Findings support the assertion that disruptions in secondary processes such as strategy use and attentional selection may have played a role in previous reports of WM impairment in ASD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Diffusion Tensor Imaging And Tractography In Autistic, Dysphasic, And Healthy Control Children.

BackgroundDiffusion tensor imaging (DTI) is a powerful tool for investigating brain anatomical connectivity. The aim of our study was to compare brain connectivity among children with autism spectrum disorders (ASD), developmental dysphasia (DD), and healthy controls (HC) in the following tracts: the arcuate fasciculus (AF), inferior frontal occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), and uncinate fasciculus (UF).MethodsOur sample consisted of 113 children with a mean age 8.7±2.2 years (77 boys, 36 girls), divided into three subgroups: ASD (n=39), DD (n=36), and HC (n=38). The International Classification of Diseases, 10th ed. was used to make clinical diagnoses. DTI images were collected using a 1.5 T Phillips Achieva MR imaging system.ResultsDetailed analyses of fractional anisotropy (FA) revealed significant differences among the ASD, DD, and HC groups in the left AF (p=0.014) and right AF (p=0.001), the left IFOF (p<0.001) and right IFOF (p<0.001), the left ILF (p<0.001) and right ILF (p<0.001), but not in the UF. Post-hoc analyses revealed three patterns of FA differences among the groups: (1) in the right AF, right IFOF, and right ILF, FA was significantly lower in the ASD group compared to the DD and HC groups; however, there was no difference in FA between DD and HC; (2) in the left AF and left IFOF, FA was significantly lower in the ASD than in the HC group, but there were no differences between DD vs HC nor DD vs ASD; and (3) in the left ILF, no difference in FA was seen between ASD and DD, but FA in both was significantly lower than in the HC.ConclusionMicrostructural white matter properties differed between ASD vs DD and HC subjects. The tract where FA impairment in ASD and DD subjects was the most similar was the left ILF.

Delayed M50/M100 evoked response component latency in minimally verbal/nonverbal children who have autism spectrum disorder

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.

Anterior cingulate cortex dysfunction underlies social deficits in Shank3 mutant mice

Social deficit is a core clinical feature of autism spectrum disorder (ASD) but the underlying neural mechanisms remain largely unclear. We demonstrate that structural and functional impairments occur in glutamatergic synapses in the pyramidal neurons of the anterior cingulate cortex (ACC) in mice with a mutation in Shank3, a high-confidence candidate ASD gene. Conditional knockout of Shank3 in the ACC was sufficient to generate excitatory synaptic dysfunction and social interaction deficits, whereas selective enhancement of ACC activity, restoration of SHANK3 expression in the ACC, or systemic administration of an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor-positive modulator improved social behavior in Shank3 mutant mice. Our findings provide direct evidence for the notion that the ACC has a role in the regulation of social behavior in mice and indicate that ACC dysfunction may be involved in social impairments in ASD.

Quantifying individual differences in brain morphometry underlying symptom severity in Autism Spectrum Disorders

The neurobiology of heterogeneous neurodevelopmental disorders such as autism spectrum disorders (ASD) are still unclear. Despite extensive efforts, most findings are difficult to reproduce due to high levels of individual variance in phenotypic expression. To quantify individual differences in brain morphometry in ASD, we implemented a novel subject-level, distance-based method on subject-specific attributes. In a large multi-cohort sample, each subject with ASD (n = 100; n = 84 males; mean age: 11.43 years; mean IQ: 110.58) was strictly matched to a control participant (n = 100; n = 84 males; mean age: 11.43 years; mean IQ: 110.70). Intrapair Euclidean distance of MRI brain morphometry and symptom severity measures (Social Responsiveness Scale) were entered into a regularised machine learning pipeline for feature selection, with rigorous out-of-sample validation and permutation testing. Subject-specific structural morphometry features significantly predicted individual variation in ASD symptom severity (19 cortical thickness features, p = 0.01, n = 5000 permutations; 10 surface area features, p = 0.006, n = 5000 permutations). Findings remained robust across subjects and were replicated in validation samples. Identified cortical regions implicate key hubs of the salience and default mode networks as neuroanatomical features of social impairment in ASD. Present results highlight the importance of subject-level markers in ASD, and offer an important step forward in understanding the neurobiology of heterogeneous disorders.

Effectiveness of the Program "Acqua Mediatrice di Comunicazione" (Water as a Mediator of Communication) on Social Skills, Autistic Behaviors and Aquatic Skills in ASD Children.

The study aims to analyze the effectiveness of a swimming program on interpersonal skills, autistic mannerisms, and aquatic abilities in children with autism spectrum disorders (ASD). Research on aquatic therapy showed improvements in motor skills, whereas there is little evidence of effectiveness of this approach on social impairments of ASD. Participants included 25 children, 13 in the experimental group and 12 in the control group, matched for gender, age and autism score. The results showed an advantage in the relational skills for the experimental group at the post-test. The tendency to ameliorate other symptomatology, e.g., autonomy and negative behaviors, persisted at follow-up. Likewise, positive changes in aquatic skills were maintained 6 months after the end of the program.

Social Impairments in Mental Disorders: Recent Developments in Studying the Mechanisms of Interactive Behavior

Most mental disorders are associated with impairments in social functioning. Paradigms developed to study social functioning in laboratory settings mostly put participants in a detached observer point of view. However, some phenomena are inherently interactive and studying full-blown reciprocal interactions may be indispensable to understand social deficits in psychopathology. We conducted a narrative review on recent developments in the field of experimental clinical psychology and clinical social neuroscience that employs a second-person approach to studying social impairments in Autism Spectrum Disorder (ASD), Personality Disorder, Social Anxiety Disorder (SAD), and Schizophrenia. Recent developments in methodological, analytical, and technical approaches, such as dual eye-tracking, mobile eye-tracking, live video-feed, hyperscanning, or motion capture allow for a more ecologically valid assessment of social functioning. In individuals with ASD, these methods revealed reduced sensitivity to the presence of a real interaction partner as well as diminished behavioral and neural synchronicity with interaction partners. Initial evidence suggests that interactive paradigms might be a powerful tool to reveal reduced interpersonal sensitivity in Personality Disorders and increased interpersonal sensitivity in individuals with SAD. A shift towards adapting a second-person account has clearly benefitted research on social interaction in psychopathology. Several studies showed profound differences in behavioral and neural measures during actual social interactions, as compared to engaging participants as mere observers. While research using truly interactive paradigms is still in its infancy, it holds great potential for clinical research on social interaction. We review studies adopting a second-person account of social interaction in clinical psychology. Studies show profound differences between actual social interactions and mere observations. The full extent of impairments in social functioning unfolds only in complex social interactions. New methodological developments hold great potential for research on social interaction deficits. We review studies adopting a second-person account of social interaction in clinical psychology. Studies show profound differences between actual social interactions and mere observations. The full extent of impairments in social functioning unfolds only in complex social interactions. New methodological developments hold great potential for research on social interaction deficits.

Self-reported social impairments predict depressive disorder in adults with autism spectrum disorder.

In adults with autism spectrum disorder, co-occurring psychiatric conditions are prevalent, and depression is one of the most common co-occurring disorders. This study examined the relationship between depression and cognitive ability, autism symptom severity, and self-reported social impairments in autism spectrum disorder. A total of 33 adults with autism spectrum disorder and 28 adults with typical development completed a standardized psychiatric interview, cognitive test, measure of clinician-rated autism symptom severity, and self-report of social impairments. Nine participants with autism spectrum disorder (27%) met the criteria for a depressive disorder (autism spectrum disorder + depressive disorder). Relatively more females with autism spectrum disorder had a co-occurring depressive disorder. The typical development group had a higher intelligence quotient than the autism spectrum disorder group, but the autism spectrum disorder + depressive disorder group did not differ from the typical development or autism spectrum disorder group. While the autism spectrum disorder + depressive disorder group had lower clinician-rated autism symptom severity than the autism spectrum disorder group, the autism spectrum disorder + depressive disorder group reported more social impairments than the autism spectrum disorder group. Self-reported social impairments predicted depression in adults with autism spectrum disorder when accounting for symptom severity and cognitive ability. These findings suggest that more self-perceived social impairments are related to depressive disorders in autism spectrum disorder, and may help clinicians identify individuals who are vulnerable in developing a co-occurring depressive disorder. Future directions include follow-up studies with larger cohorts and longitudinal designs to support inferences regarding directionality of these relationships.

Lesser suppression of response to bright visual stimuli and visual abnormality in children with autism spectrum disorder: a magnetoencephalographic study

BackgroundVisual abnormality is a common sensory impairment in autism spectrum disorder (ASD), which may cause behavioral problems. However, only a few studies exist on the neural features corresponding to the visual symptoms in ASD. The purpose of this study was to investigate the relationship between cortical responses to visual stimuli and visual abnormality to examine the neurophysiological mechanisms of the visual abnormality in ASD.MethodsTwenty-two high-functioning children with ASD (10.95 ± 2.01 years old) and 23 age-matched typically developing (TD) children (10.13 ± 2.80 years old) participated in this study. We measured the cortical responses (i.e., activated intensity and attenuation ratio) elicited by the Original visual image and other two types of bright images (the Dot noise or Blind image, which includes overlapped particles onto the Original image or the enhanced-brightness version of the Original image, respectively) using magnetoencephalography.ResultsThe severity of visual abnormalities was significantly associated with behavioral problems in children with ASD. In addition, we found the increased cortical activation in response to the Original image in the left supramarginal gyrus (SMG) and middle temporal gyrus in children with ASD. However, there were no inter-group differences in the primary visual and medial orbitofrontal cortices. Furthermore, when we compared cortical responses according to the type of images, children with ASD showed lesser attenuation of the activated intensities than children with TD in response to the bright images compared with the Original image in the right SMG. These attenuation ratios (Dot noise/Original and Blind/Original) were also associated with the severity of visual abnormalities.ConclusionsOur results show that dysfunction of stimulus-driven neural suppression plays a crucial role in the neural mechanism of visual abnormality in children with ASD. To the best of our knowledge, this is the first magnetoencephalography study to demonstrate the association between the severity of visual abnormality and lower attenuation ratios in children with ASD. Our results contribute to the knowledge of the mechanisms underlying visual abnormality in children with ASD, and may therefore lead to more effective diagnosis and earlier intervention.

Mechanisms of voice control related to prosody in autism spectrum disorder and first-degree relatives.

Differences in prosody (e.g., intonation, rhythm) are among the most obvious language‐related impairments in autism spectrum disorder (ASD), and significantly impact communication. Subtle prosodic differences have also been identified in a subset of clinically unaffected first‐degree relatives of individuals with ASD, and may reflect genetic liability to ASD. This study investigated the neural basis of prosodic differences in ASD and first‐degree relatives through analysis of feedforward and feedback control involved in the planning, production, self‐monitoring, and self‐correction of speech by using a pitch‐perturbed auditory feedback paradigm during sustained vowel and speech production. Results revealed larger vocal response magnitudes to pitch‐perturbed auditory feedback across tasks in ASD and ASD parent groups, with differences in sustained vowel production driven by parents who displayed subclinical personality and language features associated with ASD (i.e., broad autism phenotype). Both ASD and ASD parent groups exhibited increased response onset latencies during sustained vowel production, while the ASD parent group exhibited decreased response onset latencies during speech production. Vocal response magnitudes across tasks were associated with prosodic atypicalities in both individuals with ASD and their parents. Exploratory event‐related potential (ERP) analyses in a subgroup of participants during the sustained vowel task revealed reduced P1 ERP amplitudes in the ASD group, with similar trends observed in parents. Overall, results suggest underdeveloped feedforward systems and neural attenuation in detecting audio‐vocal feedback may contribute to ASD‐related prosodic atypicalities. Importantly, results implicate atypical audio‐vocal integration as a marker of genetic risk to ASD, evident in ASD and among clinically unaffected relatives. Autism Res 2019, 12: 1192–1210. © 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc.Lay SummaryPrevious research has identified atypicalities in prosody (e.g., intonation) in individuals with ASD and a subset of their first‐degree relatives. In order to better understand the mechanisms underlying prosodic differences in ASD, this study examined how individuals with ASD and their parents responded to unexpected differences in what they heard themselves say to modify control of their voice (i.e., audio‐vocal integration). Results suggest that disruptions to audio‐vocal integration in individuals with ASD contribute to ASD‐related prosodic atypicalities, and the more subtle differences observed in parents could reflect underlying genetic liability to ASD.

Resting-State Brain Network Dysfunctions Associated With Visuomotor Impairments in Autism Spectrum Disorder.

Background: Individuals with autism spectrum disorder (ASD) show elevated levels of motor variability that are associated with clinical outcomes. Cortical–cerebellar networks involved in visuomotor control have been implicated in postmortem and anatomical imaging studies of ASD. However, the extent to which these networks show intrinsic functional alterations in patients, and the relationship between intrinsic functional properties of cortical–cerebellar networks and visuomotor impairments in ASD have not yet been clarified.Methods: We examined the amplitude of low-frequency fluctuation (ALFF) of cortical and cerebellar brain regions during resting-state functional MRI (rs-fMRI) in 23 individuals with ASD and 16 typically developing (TD) controls. Regions of interest (ROIs) with ALFF values significantly associated with motor variability were identified for for patients and controls respectively, and their functional connectivity (FC) to each other and to the rest of the brain was examined.Results: For TD controls, greater ALFF in bilateral cerebellar crus I, left superior temporal gyrus, left inferior frontal gyrus, right supramarginal gyrus, and left angular gyrus each were associated with greater visuomotor variability. Greater ALFF in cerebellar lobule VIII was associated with less visuomotor variability. For individuals with ASD, greater ALFF in right calcarine cortex, right middle temporal gyrus (including MT/V5), left Heschl's gyrus, left post-central gyrus, right pre-central gyrus, and left precuneus was related to greater visuomotor variability. Greater ALFF in cerebellar vermis VI was associated with less visuomotor variability. Individuals with ASD and TD controls did not show differences in ALFF for any of these ROIs. Individuals with ASD showed greater posterior cerebellar connectivity with occipital and parietal cortices relative to TD controls, and reduced FC within cerebellum and between lateral cerebellum and pre-frontal and other regions of association cortex.Conclusion: Together, these findings suggest that increased resting oscillations within visuomotor networks in ASD are associated with more severe deficits in controlling variability during precision visuomotor behavior. Differences between individuals with ASD and TD controls in the topography of networks showing relationships to visuomotor behavior suggest atypical patterns of cerebellar–cortical specialization and connectivity in ASD that underlies previously documented visuomotor deficits.

A Spectrotemporal Correlate of Language Impairment in Autism Spectrum Disorder.

This study introduces an objective neurophysiological marker of language ability, the integral of event-related desynchronization in the 5-20Hz band during 0.2-1seconds post auditory stimulation with interleaved word/non-word tokens. This measure correlates with clinical assessment of language function in both ASD and neurotypical pediatric populations. The measure does not appear related to general cognitive ability nor autism symptom severity (beyond degree of language impairment). We suggest that this oscillatory brain activity indexes lexical search and thus increases with increased search in the mental lexicon. While specificity for language impairment in ASD remains to be determined, such an objective index has potential utility in low functioning individuals with ASD and young children during language acquisition.

A Review of Functional and Structural Neurobiology of the Action Observation Network in Autism Spectrum Disorder and Developmental Coordination Disorder.

Recent research has reported motor impairment similarities between children with developmental coordination disorder (DCD) and a subgroup of individuals with autism spectrum disorder (ASD). However, there is a debate as to whether DCD is a co-occurring diagnosis in individuals with ASD and motor impairments (ASDd), or if motor impairments in ASD are distinct from DCD. However, the etiology of motor impairments is not well understood in either disorder. Clarifying comorbidities in ASD is important to determine different etiopathological phenotyping clusters in ASD and to understand the variety of genetic and environmental factors that contribute to the disorder. Furthermore, this distinction has important therapeutic relevance. Here we explore the current neuroimaging findings in ASD and DCD and discusses possible neural mechanisms that underlie similarities and differences between the disorders.

Linguistic markers of autism in girls: evidence of a \u201cblended phenotype\u201d during storytelling

BackgroundNarrative abilities are linked to social impairment in autism spectrum disorder (ASD), such that reductions in words about cognitive processes (e.g., think, know) are thought to reflect underlying deficits in social cognition, including Theory of Mind. However, research suggests that typically developing (TD) boys and girls tell narratives in sex-specific ways, including differential reliance on cognitive process words. Given that most studies of narration in ASD have been conducted in predominantly male samples, it is possible that prior results showing reduced cognitive processing language in ASD may not generalize to autistic girls. To answer this question, we measured the relative frequency of two kinds of words in stories told by autistic girls and boys: nouns (words that indicate object-oriented storytelling) and cognitive process words (words like think and know that indicate mentalizing or attention to other peoples’ internal states).MethodsOne hundred two verbally fluent school-aged children [girls with ASD (N = 21) and TD (N = 19), and boys with ASD (N = 41) and TD (N = 21)] were matched on age, IQ, and maternal education. Children told a story from a sequence of pictures, and word frequencies (nouns, cognitive process words) were compared.ResultsAutistic children of both sexes consistently produced a greater number of nouns than TD controls, indicating object-focused storytelling. There were no sex differences in cognitive process word use in the TD group, but autistic girls produced significantly more cognitive process words than autistic boys, despite comparable autism symptom severity. Thus, autistic girls showed a unique narrative profile that overlapped with autistic boys and typical girls/boys. Noun use correlated significantly with parent reports of social symptom severity in all groups, but cognitive process word use correlated with social ability in boys only.ConclusionThis study extends prior research on autistic children’s storytelling by measuring sex differences in the narratives of a relatively large, well-matched sample of children with and without ASD. Importantly, prior research showing that autistic children use fewer cognitive process words is true for boys only, while object-focused language is a sex-neutral linguistic marker of ASD. These findings suggest that sex-sensitive screening and diagnostic methods—preferably using objective metrics like natural language processing—may be helpful for identifying autistic girls, and could guide the development of future personalized treatment strategies.

L’évaluation sensori-psychomotrice dans l’autisme : un nouvel outil d’aide au diagnostic fonctionnel

IntroductionPsychomotor impairments in Autism Spectrum Disorders (ASD) have frequently been described in scientific literature. Such deficits impact upon the development of social motor function and interfere with the ability to adjust to everyday life. The inclusion of sensory-motor signs in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) confirms their importance in the diagnosis of ASD. Previous literature has shown the presence precocity of these signs, sometimes before the alteration of the social communication. To our knowledge, there are no existing clinical tools to measure sensory-psychomotor deficit, specifically in ASD. The current paper presents the construction and validation of a new scale, designed to evaluate sensory-psychomotor signs in Autism: ‘the Sensory-psychomotor Particularities Scale in Autism’ (SPSA). MethodThe scale is composed of 160 items describing common sensory-psychomotor signs in autism. These items are grouped into 20 variables: touch, nociception, vestibular sensitivity, proprioceptive sensitivity, vision, auditory, multimodality, tone, posture, balance, global coordination, manual dexterity, body schema, bodily self-consciousness, relational adjustment, emotional expression, use of objects, space, time and tonico-emotional regulation. For each item, the psychomotor therapist evaluated sensori-psychomotor signs according to a five-level Likert scale (0=“the sign is never expressed by the person”, 1=“weakly expressed”, 2=“moderately expressed”, 3=“severely expressed” and 4=“the sign is very characteristic of the person and very severely expressed”). This is completed by a family interview in order to assess the impact of these signs on everyday situations. The study included 111 children with autism. The presence of neurological and genetic diseases was exclusion criteria. For each child, a global developmental evaluation was carried out by an expert clinical team specializing in ASD. Standardized clinical tools were used: Autism Diagnostic Observation Schedule (ADOS), Childhood Autism Rating Scale (CARS), Behavior Summarized Evaluation scale (BSE-R), Repeated and Restricted Behavior scale (RRB), Movement Assessment Battery for Children (M-ABC), Motor Development Rating scale (MDR), Sensory Profile (SP). Developmental quotients (DQ) were evaluated using various tests depending on age and ability. ResultsFactor analysis produced three clinically relevant factors: F1: “sensory-emotional synchronization”, F2: “multisensory integration” and F3: “motor skills”: each containing a similar quantity of items. They account for roughly equal percentages of variance (18.9%, 18.0%, 16.8%, respectively). The factorial structure does not change if the 26 children with comorbid developmental coordination disorder are removed. The three factors show good internal consistency and excellent inter-rater reliability. F1 is comprised of 6 items: touch, nociception, proprioceptive sensitivity, vision, emotional expression and tonico-emotional regulation. This factor is significantly associated with items of the Sensory Profile (touch processing, poor registration, sensory seeking). F2 is comprised of 5 items: multimodality, bodily self-consciousness, relational adjustment, use of objects and space. This factor is associated with ADOS, BSE-R and RRB scores, and the item “touch processing” of the Sensory Profile. F3 is comprised of 4 items: tone, posture, global coordination, manual dexterity. This factor is associated with the M-ABC, the MDR and the item “low endurance” of the Sensory Profile. ConclusionThe SPSA is a relevant clinical tool to assess the severity of sensory-psychomotor clinical signs in order to describe the individual profiles of children with ASD. It represents a critical step in advancing knowledge of the complex and heterogeneous pattern of psychomotor development in autism. It could make a valuable contribution to the field, both in research and clinical practice.

ERP evidence of semantic processing in children with ASD

25% of children with autism spectrum disorder (ASD) remain minimally verbal (MV), despite intervention. Electroencephalography can reveal neural mechanisms underlying language impairment in ASD, potentially improving our ability to predict language outcomes and target interventions. Verbal (V) and MV children with ASD, along with an age-matched typically developing (TD) group participated in a semantic congruence ERP paradigm, during which pictures were displayed followed by the expected or unexpected word.An N400 effect was evident in all groups, with a shorter latency in the TD group. A late negative component (LNC) also differentiated conditions, with a group by condition by region interaction. Post hoc analyses revealed that the LNC was present across multiple regions in the TD group, in the mid-frontal region in MVASD, and not present in the VASD group. Cluster analysis identified subgroups within the ASD participants. Two subgroups showed markedly atypical patterns of processing, one with reversed but robust differentiation of conditions, and the other with initially reversed followed by typical differentiation. Findings indicate that children with ASD, including those with minimal language, showed EEG evidence of semantic processing, but it was characterized by delayed speed of processing and limited integration with mental representations.

Conditional knockout of UBC13 produces disturbances in gait and spontaneous locomotion and exploration in mice

Here we have characterized the functional impairments resulting from conditional knockout of the ubiquitin-conjugating E2 enzyme (UBC13) in rodent cerebellar granule neurons, which greatly increases the parallel fiber presynaptic boutons and functional parallel fiber/Purkinje cell synapses. We report that conditional UBC13 knockout mice exhibit reliable deficits on several gait-related variables when their velocity of ambulation is tightly controlled by a moving treadmill and by restricting space for movement. Selected gait parameters and movement patterns related to spontaneous exploration in an open field may also be affected in conditional UBC13 knockout mice. Analysis of open-field data as a function of test session half using force-plate actometer instrumentation suggest that conditional UBC13 knockout mice have alterations in emotionality, possibly affecting gait and movement variables. These findings suggest that conditional UBC13 knockout mice represent a valuable platform for assessing the effects of disturbances in cerebellar granule cell circuitry on gait and other aspects of locomotion. Also, the possibility that psychological factors such as altered emotionality may impact gait and movement patterns in these mice suggest that these mice may provide a useful model for evaluating analogous behavioral impairments in autism spectrum disorders and other neurodevelopmental syndromes associated with deregulation of ubiquitin signaling.

Impaired Recognition of Negative Facial Expressions is Partly Related to Facial Perception Deficits in Adolescents with High-Functioning Autism Spectrum Disorder.

Accumulating studies have reported facial emotion recognition or facial perception impairments in autism spectrum disorder (ASD). To clarify the specificity of the emotion recognition impairment, this study examined the relationships between facial emotion recognition and facial perception abilities in ASD. Twenty-two adolescents with high-functioning ASD (20 males) and 22 typically developing (TD) adolescents (16 males) aged 11-18years undertook a facial emotion labeling task and a facial perception test. We found that adolescents with ASD had deficits in recognizing negative facial expressions, which correlated with both facial perception deficits and severity of social impairment. In addition, the emotion recognition deficits remained after adjusting for facial perception performance. Thus, our findings suggest an emotion-specific impairment in facial emotion recognition in ASD.

Deconstructing Theory-of-Mind Impairment in High-Functioning Adults with Autism

Inferring the beliefs, desires, and intentions of other people ("theory of mind," ToM) requires specialized psychological processes that represent the minds of others as distinct from our own [1-3]. ToM is engaged ubiquitously in our everyday social behavior and features a specific developmental trajectory [4] that is notably delayed in children with autism spectrum disorder (ASD) [5, 6]. In healthy individuals, model-based analyses of social learning and decision-making have successfully elucidated specific computational components of ToM processing [7-11]. However, the use of this approach to study ToM impairment in ASD has been extremely limited [10, 12]. To better characterize specific ToM impairment in ASD, we developed a novel learning task and applied model-based analyses in high-functioning adults with ASD and matched healthy controls. After completing a charitable donation task, participants performed a "mentalizer" task in which they observed another person (the agent) complete the same charity task. The mentalizer task probed the participants' ability to acquire and use ToM representations. To accurately predict agent behavior, participants needed to dynamically track the agent's beliefs (true or false) about an experimental context that varied over time and use that information to infer the agent's intentions from their actions. ASD participants were specifically impaired at using their estimates of agent belief to learn agent intentions, though their ability to track agent belief was intact and their reasoning about belief and intentions was rational. Furthermore, model parameters correlated with aspects of social functioning, e.g., ADOS severity scores [13]. Together, these results identify novel, and more specific, targets for future research.

Reprint of: Serotonin as a link between the gut-brain-microbiome axis in autism spectrum disorders

Autism-spectrum disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social communication and repetitive patterns of behavior. ASD is, however, often associated with medical comorbidities and gastrointestinal (GI) dysfunction is among the most common. Studies have demonstrated a correlation between GI dysfunction and the degree of social impairment in ASD. The etiology of GI abnormalities in ASD is unclear, though the association between GI dysfunction and ASD-associated behaviors suggest that overlapping developmental defects in the brain and the intestine and/or a defect in communication between the enteric and central nervous systems (ENS and CNS, respectively), known as the gut-brain axis, could be responsible for the observed phenotypes. Brain-gut abnormalities have been increasingly implicated in several disease processes, including ASD. As a critical modulator of ENS and CNS development and function, serotonin may be a nexus for the gut-brain axis in ASD. This paper reviews the role of serotonin in ASD from the perspective of the ENS. A murine model that has been demonstrated to possess brain, behavioral and GI abnormalities mimicking those seen in ASD harbors the most common serotonin transporter (SERT) based mutation (SERT Ala56) found in children with ASD. Discussion of the gut-brain manifestations in the SERT Ala56 mice, and their correction with developmental administration of a 5-HT4 agonist, are also addressed in conjunction with other future directions for diagnosis and treatment.