Autism Spectrum Disorder Impairment Research Articles

A Case of Autism Spectrum Disorder Treated with Theridion currasavicum Prescribed on the Basis of Group Approach

Abstract Background Autism spectrum disorder (ASD) is a pervasive developmental disorder of unknown aetiology. There is a growing prevalence of ASD globally. Currently, there are no specific treatments that can address the core impairments of ASD. Case Summary A 5-year male child was brought to outpatient department with complaints of irritability, restlessness, howling, repeating words spoken to him, repeating phrases, hand flapping, self-hurting and hurting others, climbing stairs repeatedly, repeated drawing of squares everywhere, poor social interaction, poor peer-play and inappropriate playing with toys. The case was diagnosed as ASD and was assessed with the autism treatment evaluation checklist (ATEC) at baseline and follow-up visits. The case was treated with Theridion currasavicum in centesimal scale. ATEC score at baseline of 118 turned to 69 at the 12th month and 42 after 24 months of treatment. The remedy was repeated during monthly visits in ascending potencies. The child improved in the domains of social interaction, communication, repetitive stereotype movements, restricted interests and general health. The likelihood of causal relationship between intervention and outcome has been discussed as per modified Naranjo criteria for homoeopathy. This case report highlights the usefulness of the group approach and aetiological prescription as one way of arriving at the similimum in children with autism.

Global Sensory Features are Linked to Executive and Attentional Impairments in Autism Spectrum Disorders.

Sensory features, executive and attentional impairments are frequently reported in individuals with autism spectrum disorders (ASD). However, little is known about their complex relationships. In this study, we aim to examine the executive and attentional difficulties related to distinct sensory profiles. We identified sensory profiles with a Latent Profile Analysis (LPA) based on scores on the Short Sensory Profile (SSP) questionnaire in 95 children with ASD aged 6 to 17years. Executive and attention functions were assessed using the Behavior Rating Inventory of Executive Functions (BRIEF) questionnaire and Attention-Deficit Hyperactivity Disorder Rating Scale (ADHD-RS). A three-cluster solution based on raw SSP scores identified a "high'', a "medium" and a "low'' SSP profile. We found a significant relationship between executive functions, attentional skills and the global severity of sensory features, reinforcing findings of previous studies in the literature. A two-cluster solution based on normalized SSP (i.e. equalized for the global severity) identified distinct sensory profiles, mainly discriminated by the score of underresponsive/seeks sensation. We found no significant difference between these two clusters for the BRIEF and ADHD-RS related scores. Our study suggests that the heterogeneity of sensory features in ASD may not be explained by differences in executive and attention functions. Future studies are needed to refine the link between sensory features and executive functions in autism.

The development of social-conversational skills in children with autism spectrum disorder: similarities and differences with typically developing children and late talkers. Pilot study.

Many studies have emphasized the importance of the development of pragmatic skills in young children. Pragmatic deficits, reflected in poor conversational skills, are considered the hallmark of language impairment in Autism Spectrum Disorder (ASD). Our study has compared the assertive and responsive skills of a group of 600 typically developing children, 83 late talkers (LT) and 29 children with ASD (of which 24 boys and 5 girls) aged between 27 and 60 months using the questionnaires the "Child's First Vocabulary- Gestures, Words and Phrases"- PVB and "The Child's Socio-Conversational Skills"- ASCB. The analysis of the results showed that the socio-conversational abilities of children with autism improve with increasing age, that the gap in these abilities between children with typical development and those with ASD is very wide and the differences between the two samples are statistically significant. Moreover, the percentage of LTs with immature assertive and responsive skills is lower than the percentage of autistic children; in fact, despite difficulties in lexical and morphosyntactic development, the absence of deficits in social interaction allows LTs to perform better.

Neural circuit disruptions of eye gaze processing in autism spectrum disorder and schizophrenia: An activation likelihood estimation meta-analysis

BackgroundImpairment in social cognition, particularly eye gaze processing, is a shared feature common to autism spectrum disorder (ASD) and schizophrenia. However, it is unclear if a convergent neural mechanism also underlies gaze dysfunction in these conditions. The present study examined whether this shared eye gaze phenotype is reflected in a profile of convergent neurobiological dysfunction in ASD and schizophrenia. MethodsActivation likelihood estimation (ALE) meta-analyses were conducted on peak voxel coordinates across the whole brain to identify spatial convergence. Functional coactivation with regions emerging as significant was assessed using meta-analytic connectivity modeling. Functional decoding was also conducted. ResultsFifty-six experiments (n = 30 with schizophrenia and n = 26 with ASD) from 36 articles met inclusion criteria, which comprised 354 participants with ASD, 275 with schizophrenia and 613 healthy controls (1242 participants in total). In ASD, aberrant activation was found in the left amygdala relative to unaffected controls during gaze processing. In schizophrenia, aberrant activation was found in the right inferior frontal gyrus and supplementary motor area. Across ASD and schizophrenia, aberrant activation was found in the right inferior frontal gyrus and right fusiform gyrus during gaze processing. Functional decoding mapped the left amygdala to domains related to emotion processing and cognition, the right inferior frontal gyrus to cognition and perception, and the right fusiform gyrus to visual perception, spatial cognition, and emotion perception. These regions also showed meta-analytic connectivity to frontoparietal and frontotemporal circuitry. ConclusionAlterations in frontoparietal and frontotemporal circuitry emerged as neural markers of gaze impairments in ASD and schizophrenia. These findings have implications for advancing transdiagnostic biomarkers to inform targeted treatments for ASD and schizophrenia.

Abnormal functional connectivity of the reward network is associated with social communication impairments in autism spectrum disorder: A large-scale multi-site resting-state fMRI study

BackgroundThe social motivation hypothesis proposes that the social deficits of autism spectrum disorder (ASD) are related to reward system dysfunction. However, functional connectivity (FC) patterns of the reward network in ASD have not been systematically explored yet. MethodsThe reward network was defined as eight regions of interest (ROIs) per hemisphere, including the nucleus accumbens (NAc), caudate, putamen, anterior cingulate cortex (ACC), ventromedial prefrontal cortex (vmPFC), orbitofrontal cortex (OFC), amygdala, and insula. We computed both the ROI-wise resting-state FC and seed-based whole-brain FC in 298 ASD participants and 348 typically developing (TD) controls from the Autism Brain Imaging Data Exchange I dataset. Two-sample t-tests were applied to obtain the aberrant FCs. Then, the association between aberrant FCs and clinical symptoms was assessed with Pearson's correlation or Spearman's correlation. In addition, Neurosynth Image Decoder was used to generate word clouds verifying the cognitive functions of the aberrant pathways. Furthermore, a three-way multivariate analysis of variance (MANOVA) was conducted to examine the effects of gender, subtype and age on the atypical FCs. ResultsFor the within network analysis, the left ACC showed weaker FCs with both the right amygdala and left NAc in ASD compared with TD, which were negatively correlated with the Autism Diagnostic Observation Schedule (ADOS) total scores and Social Responsiveness Scale (SRS) total scores respectively. For the whole-brain analysis, weaker FC (i.e., FC between the left vmPFC and left calcarine gyrus, and between the right vmPFC and left precuneus) accompanied by stronger FC (i.e., FC between the left caudate and right insula) were exhibited in ASD relative to TD, which were positively associated with the SRS motivation scores. Additionally, we detected the main effect of age on FC between the left vmPFC and left calcarine gyrus, of subtype on FC between the right vmPFC and left precuneus, of age and age-by-gender interaction on FC between the left caudate and right insula. ConclusionsOur findings highlight the crucial role of abnormal FC patterns of the reward network in the core social deficits of ASD, which have the potential to reveal new biomarkers for ASD.

The Physiology of Cognition in Autism Spectrum Disorder: Current and Future Challenges.

Cognitive impairment is among the most challenging characteristics of autism spectrum disorder (ASD). Although ASD is one of the common neurodevelopmental disorders, we are still behind in diagnosing and treating cognitive impairment in ASD. Cognitive impairment in ASD varies, meaning it could be at the sensory perception level to cognitive processing, learning, and memory. There are no diagnostic criteria for cognitive impairment that are specific to ASD. The leading causes of cognitive impairment in ASD could be neurological, immune, and gastrointestinal dysfunction. Immune dysfunction might lead to neuroinflammation, affecting neural connectivity, glutamate/gamma-aminobutyric acid (GABA) balance, and plasticity. The gut-brain axes are essential in the developing brain. Special retinal changes have recently been detected in ASD, which need clinical investigation to find their possible role in early diagnosis. Early intervention is crucial for ASD cognitive dysfunction. Due to the heterogeneity of the disease, the clinical manifestation of ASD makes it difficult for clinicians to develop gold-standard diagnostic and therapeutic criteria. We suggest a triad for diagnosis, which includes clinical tests for immune and gastrointestinal dysfunction biomarkers, clinical examination for the retina, and an objective neurocognitive evaluation for ASD, and to develop a treatment strategy involving these three aspects. Developing clear treatment criteria for cognitive impairment for ASD would improve the quality of life of ASD people and their caregivers and would delay or prevent dementia-related disorders in ASD people.

The effects of abnormal visual experience on neurodevelopmental disorders.

Normal visual development is supported by intrinsic neurobiological mechanisms and by appropriate stimulation from the environment, both of which facilitate the maturation of visual functions. However, an offset of this balance can give rise to visual disorders. Therefore, understanding the factors that support normal vision during development and in the mature brain is important, as vision guides movement, enables social interaction, and allows children to recognize and understand their environment. In this paper, we review fundamental mechanisms that support the maturation of visual functions and discuss and draw links between the perceptual and neurobiological impairments in autism spectrum disorder (ASD) and schizophrenia. We aim to explore how this is evident in the case of ASD, and how perceptual and neurobiological deficits further degrade social ability. Furthermore, we describe the altered perceptual experience of those with schizophrenia and evaluate theories of the underlying neural deficits that alter perception.

Hand grip strengthening exercises on fine motor skills in children with autism spectrum disorder

Background. Movement impairments in autism spectrum disorder (ASD) are manifested as both delays and deficits, with delays found in gross motor, fine motor and speech domains and deficits found in coordination, postural control and gait. Functional fine motor task is dependent on hand grip strength (HGS) which is found to be decreased. Therapeutic strategies focus primarily on sensory integration issues but HGS is not comprehensively addressed in improving fine motor skills (FMS). Objective. The aim of the study was to analyse the effect of hand grip strengthening exercises on improving FMS in children with ASD. Materials and Methods. This interventional study was carried out in 27 children with ASD who were recruited from Vidya sudha – Centre for children with special needs. After including in the study, level of FMS was assessed by Peabody Developmental Motor Scale (PDMS-2) and HGS was quantified with Martin Vigorimeter. Control group received conventional therapy and Intervention group received hand grip strengthening exercises along with routine therapy for duration of 6 weeks and HGS and level of FMS were reassessed with same outcome measures. Results. Paired t test showed statistically significant change of HGS in Intervention group and FMS of both the group with p < 0.05. Unpaired t test showed statistically significant change of HGS and FMS with p < 0.05 in Interventional group compared to control group. Conclusion. Hand grip strengthening exercises improves the HGS and has positive effect on FMS which can be included in the standard plan of care in rehabilitating children with ASD.

Altered interpersonal distance regulation in autism spectrum disorder.

Interpersonal distance regulation is an essential element of social communication. Its impairment in autism spectrum disorder (ASD) is widely acknowledged among practitioners, but only a handful of studies reported empirical research in real-life settings, focusing mainly on children. Interpersonal distance in adults with ASD and related autonomic functions received less attention. Here, we measured interpersonal distance along with heart rate variability (HRV) in adults with ASD, and tested the modulatory effects of eye-contact and attribution. Twenty-two adults diagnosed with ASD and 21 matched neurotypical controls participated in our study from October 2019 to February 2020. Our experimental design combined the modified version of the stop distance paradigm with HRV measurement controlling for eye contact between the experimenter and the participant to measure interpersonal distance. Still, we did not detect significant modulatory effect of eye contact and attribution. Our results showed a greater preferred distance in ASD. Moreover, we found lower baseline HRV and reduced HRV reactivity in ASD; however, these autonomic measurements could not predict preferred interpersonal distance. Our study highlights the importance of interpersonal space regulation in ASD: it might be considered that people with ASD need individually variable, presumably greater interpersonal distance. In addition, regardless of the distance they may have reduced autonomic regulatory capacity in social situations. Our results could help shape future experiments with sophisticated designs to grasp the complexity and underlying factors of distance regulation in typical and atypical populations.

Results of a phase Ib study of SB-121, an investigational probiotic formulation, a randomized controlled trial in participants with autism spectrum disorder

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by core impairments in social communication as well as restricted, repetitive patterns of behavior and/or interests. Individuals with ASD, which includes about 2% of the US population, have challenges with activities of daily living and suffer from comorbid medical and mental health concerns. There are no drugs indicated for the core impairments of ASD. As such, there is a significant need for the development of new medication strategies for individuals with ASD. This first-in-human placebo-controlled, double-blind, crossover study investigated the safety (primary objective) and efficacy of oral SB-121, a combination of L. reuteri, Sephadex® (dextran microparticles), and maltose administered once daily for 28 days in 15 autistic participants. SB-121 was safe and well tolerated. SB-121-associated directional improvements in adaptive behavior measured by Vineland-3 and social preference as measured with eye tracking were noted. These results provide support for further clinical evaluation of SB-121 as a treatment in autistic patients. To evaluate the safety and tolerability of multiple doses of SB-121 in subjects with autism spectrum disorder. Single-center, randomized, placebo-controlled, double-blind, crossover trial. 15 patients with autism spectrum disorder were randomized and analyzed. Daily dosing of SB-121 or placebo for 28 days, followed by approximately a 14 day washout, then 28 days of dosing with other treatment. Incidence and severity of adverse events, presence of Limosilactobacillus reuteri and Sephadex® in stool, and incidence of bacteremia with positive L. reuteri identification. Additional outcomes include changes from baseline on cognitive and behavior tests as well as biomarker levels. Adverse event rates were similar between SB-121 and placebo, with most reported as mild. There were no severe or serious adverse events. No participants had features of suspected bacteremia or notable changes in vital signs, safety laboratory, or ECG parameters from baseline. There was a statistically significant increase from baseline in the Vineland-3 Adaptive Behavior Composite score (p = 0.03) during SB-121 treatment. There was a trend for increased social/geometric viewing ratio following SB-121 treatment compared to placebo. SB-121 was safe and well tolerated. SB-121-associated directional improvements in adaptive behavior measured by Vineland-3 and social preference as measured with eye tracking were noted.Trial registration: clinicaltrials.gov Identifier: NCT04944901.

The Social Interaction Deficits in Autism Spectrum Disorder and Relevant Interventions

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder involved with genetic mutations. The individual's aberrant social communication and interaction and restricted repetitive behaviours are the manifestations. ASD can be diagnosed as young as age 2. ASD is classified as high functioning and low functioning disorders based on intelligence. Factors that influence ASD include "Theory of Mind" (ToM) and social Interaction, in which individuals with ASD have severe difficulty in understanding the thoughts of others, such as their emotions, feelings, beliefs, and opinions. This review is a retrospective study on social interaction impairment in ASD and the relevant interventions. This paper aims to evaluate social communication barriers and their impacts on school functioning, as well as the atypical social attention development during the early stage of ASD. The interventions are mainly divided into parent-child companionship, music therapy, video therapy, and active physical activity. There are still limitations in this review. Most of the methods quoted in the literature adopted cross-sectional designs, and the experimental techniques are relatively narrow. In addition, most intervention programs focused on the early developmental stage. More attention should be paid to the transition between developmental stages in the future. This review can provide some guidance to future intervention research and practice in the special education area for ASD.

Is Telehealth a Feasible Mode of Intervention Delivery to Improve Social Communication Skills in Children With Autism Spectrum Disorder? Results From a Pilot Randomized Controlled Trial

Background Children with autism spectrum disorder (ASD) demonstrate impaired verbal and nonverbal communication, deficits in emotional regulation, higher rates of repetitive behaviors, and poor motor planning and body coordination. Our past studies have demonstrated that engaging in rhythmic movement interventions can advance gross motor skills while promoting spontaneous verbalization, joint attention, and improved behavioral regulation in children with ASD. Objective This study compares the effects of 2 whole-body movement interventions to a standard-of-care intervention on social communication skills in children with ASD. Due to the pandemic, the study transitioned from face-to-face intervention (F2F) to a telehealth (TH) format. This poster will compare the efficacy of F2F and TH intervention delivery modes in promoting social communication skills. Methods A total of 45 children with ASD between 5 and 14 years old participated in a 10-week study. Children were randomly assigned to receive 8 weeks (2 sessions/week, 60-75 minutes/session) of creative movement (play), general movement (move), or seated play (create) training. Training sessions involved interactions between the child, an expert trainer, an adult model, and caregivers. Outcome measures include training-specific measures of the percent duration of socially directed and self-directed verbalization (with respect to the total verbalization time) measured during early and late training sessions as well as the type of verbalization (spontaneously initiated versus in response to partner bidding or prompting). We will also compare the magnitude of training-related change in verbalization in children seen F2F versus via TH. Results In all groups, children engaged in greater social versus self-directed verbalization during early and late training sessions. The move group showed an increase in social verbalization with respect to the total session duration from early to late sessions (mean early 11.4, SE 1.5; mean late 15.6, SE 2.0; P=.02). These improvements were in children seen F2F (67% of children) and via TH (80% of children). Within social verbalization, children in all groups verbalized more toward the researchers compared to family members during training sessions. Specifically, children in the play group demonstrated an increase in percent duration of social verbalization toward the researchers (trainer and model) from early to late session (mean early 61.9, SE 6.8; mean late 70, SE 6.8; P=.03). Children seen via TH started at lower baseline levels of social verbalization, compared to their F2F counterparts, but showed a significant increase from early to late sessions (TH: 71% and F2F: 62.5% of children improved). In terms of verbalization type, the move and create groups engaged in greater responsive verbalization compared to the play group across early and late sessions. The create group did not show any increase in social verbalization with training irrespective of intervention delivery mode. Conclusions Our preliminary data suggest that the whole-body movement interventions can be used to foster social verbalization in children with ASD. The study adds to the prepandemic evidence on the feasibility of implementation and utility of TH-based intervention delivery in the care of children with ASD. Clinicians may choose TH-based intervention delivery to build a rapport with children to address the core impairments in ASD, provided that caregivers are available during TH sessions to ensure child engagement and compliance. Conflicts of Interest None declared. Trial Registration ClinicalTrials.gov NCT04258254; https://clinicaltrials.gov/show/NCT04258254

Structural brain abnormalities and their association with language impairment in school-aged children with Autism Spectrum Disorder

Language impairment is comorbid in most children with Autism Spectrum Disorder (ASD) but its neural basis is poorly understood. Using structural magnetic resonance imaging (MRI), the present study provides the whole-brain comparison of both volume- and surface-based characteristics between groups of children with and without ASD and investigates the relationships between these characteristics in language-related areas and the language abilities of children with ASD measured with standardized tools. A total of 36 school-aged children participated in the study: 18 children with ASD and 18 age- and sex-matched typically developing controls. The results revealed that multiple regions differed between groups of children in gray matter volume, gray matter thickness, gyrification, and cortical complexity (fractal dimension). White matter volume and sulcus depth did not differ between groups of children in any region. Importantly, gray matter thickness and gyrification of language-related areas were related to language functioning in children with ASD. Thus, the results of the present study shed some light on the structural brain abnormalities associated with language impairment in ASD.

Executive function profiles of preschool children with autism spectrum disorder and attention-deficit/hyperactivity disorder: A systematic review.

Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) are both associated with differences in Executive Functioning (EF). There is lack of clarity around the specificity or overlap of EF differences in early childhood when both disorders are first emerging. This systematic review aims to delineate preschool EF profiles by examining studies comparing the EF profiles of children with and without ASD or ADHD. Five electronic databases were systematically searched (last search in May 2022) to identify published, quantitative studies of global and specific EF (Inhibition, Shifting, Working Memory (WM), Planning and Attentional Control), comparing children aged 2-6 with a diagnosis of ASD or ADHD to peers without ASD or ADHD. Thirty-one empirical studies (10 ADHD and 21 ASD studies) met criteria for inclusion. EF profiles in preschool ASD were characterised by consistent Shifting, and, in most cases, Inhibition impairments. ADHD studies consistently reported impairments in Inhibition and Planning, and in most cases WM. Findings with regards to sustained Attention and Shifting in ADHD and WM and Planning in ASD were mixed. Overall, current evidence indicates overlap but also some specificity in EF impairments in preschool ASD and ADHD. There were differences in the degree to which individual domains were impaired, with Shifting more consistently impaired in ASD, and Inhibition, WM and Planning in ADHD. Methodological issues and differences in methods of outcome measurement could potentially underlie mixed findings, as informant-based measures revealed more robust EF impairments than laboratory-based tasks.

The impact of Lego® Therapy on cognitive skills in Autism Spectrum Disorders: a brief discussion

<abstract> <p>Over the years, several interventions have been implemented, including Lego® Therapy, with the aim of supporting and implementing social and communication skills impairments in Autism Spectrum Disorders (ASD). Although recent studies have shown that the ability to learn implicitly is preserved in ASDs, no study related to Lego® Therapy has analyzed whether and how this training can also affect aspects not directly treated. In this study, we report a first attempt of assessment of Lego® Therapy's effect on the specific area of cognitive skills in an ASD child. Over a period of 12 months, a child with ASD had weekly meetings with an expert operator of Lego® aiming to improve the child's ability to communicate, reduce impulsiveness and hyper verbalism, and encourage pro-social behavior. The intervention resulted in positive outcomes that were assessed after 12 months.</p> </abstract>

Neural correlates of audiovisual speech synchrony perception and its relationship with autistic traits.

The anterior insula (AI) has the central role in coordinating attention and integrating information from multiple sensory modalities. AI dysfunction may contribute to both sensory and social impairments in autism spectrum disorder (ASD). Little is known regarding the brain mechanisms that guide multisensory integration, and how such neural activity might be affected by autistic-like symptoms in the general population. In this study, 72 healthy young adults performed an audiovisual speech synchrony judgment (SJ) task during fMRI scanning. We aimed to investigate the SJ-related brain activations and connectivity, with a focus on the AI. Compared with synchronous speech, asynchrony perception triggered stronger activations in the bilateral AI, and other frontal-cingulate-parietal regions. In contrast, synchronous perception resulted in greater involvement of the primary auditory and visual areas, indicating multisensory validation and fusion. Moreover, the AI demonstrated a stronger connection with the anterior cingulate gyrus (ACC) in the audiovisual asynchronous (vs. synchronous) condition. To facilitate asynchrony detection, the AI may integrate auditory and visual speech stimuli, and generate a control signal to the ACC that further supports conflict-resolving and response selection. Correlation analysis, however, suggested that audiovisual synchrony perception and its related AI activation and connectivity did not significantly vary with different levels of autistic traits. These findings provide novel evidence for the neural mechanisms underlying multisensory temporal processing in healthy people. Future research should examine whether such findings would be extended to ASD patients.

Autism Spectrum Disorder as a Disorder of Prediction in Sensorimotor Processing

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by persistent social interactive and communicative difficulties and repetitive, restricted behavioral patterns. Previous theories suggested impairments in two distinct sets of core abilities as an explanation for ASD. One is the delayed ability to reflect on others’ mental content, and the other is the lack of the tendency to integrate details to create meanings in contexts. In the current field, there is an emergent explanation to consider ASD as a disorder of prediction. Under this notion, two competing views proposed different accounts for the specific deficits in ASD predictive system. The Bayesian view believes that ASD individuals experience reduced priors and are less reliant on top-down information when making predictions. Alternatively, the predictive error view believes that ASD impairments result from a failure to ignore accidental prediction errors caused by environmental noise, leading to overly frequent updates and less generalizable predictions. Though both views seem credible, no previous studies have comprehensively examined their reliability in empirical evidence. Therefore, the present paper fills in the gap by reviewing the two views and their relevant psychological and neuroscientific evidence with a specific focus on sensorimotor prediction. The major conclusion is that most empirical evidence was consistent with the reduced prior proposal but not the prediction error weighing proposal. Specifically, the ASD population is resistant to reliable contextual priors even though their associative learning may remain unimpaired. In keeping with the reduced prior proposal, the ASD population showed atypical connectivity between brain areas, suggesting insufficient communication of top-down information. Additionally, subjective anxiety during the Bayesian inferential process probably hinders the prediction performance. One possible limitation of the present review is the generalizability of conclusions to the domain of social impairments. Future studies should dedicate to exploring the restrictive conditions on the reduced Bayesian prior and E/I ratio imbalance and the role of anxiety in moderating the predictive process. One practical implication is to promote context-dependent imitations in sensorimotor learning in ASD. This review can provide some insights to future intervention studies and practices for children with ASD.

Autoantibody profiling of monoamine oxidase A knockout mice, an autism spectrum disorder model

Monoamine oxidase A (MAO A) is the critical enzyme to degrade serotonin in the brain and the knockout mouse exhibits hyperserotonemia and abnormalities that are observed in autism spectrum disorder (ASD). Thus, the MAO A knockout mouse is a valuable model for studying neurological and behavioral impairments in ASD. Based on the immune dysfunction hypothesis, dysregulated humoral immunity may cause neurological impairments. To address this hypothesis, we use high-density proteome microarray to profile the serum antibodies in both wild-type and MAO A knockout mice. The distingue autoantibody signatures were observed in the MAO A knockout and wild-type controls and showed 165 up-regulated and 232 down-regulated autoantibodies. The up-regulated autoantibodies were prone to target brain tissues while down-regulated ones were enriched in sex organs. The identified autoantibodies help bridge the gap between ASD mouse models and humoral immunity, not only yielding insights into the pathological mechanisms but also providing potential biomarkers for translational research in ASD.

Peripheral Auditory Nerve Impairment in a Mouse Model of Syndromic Autism.

Dysfunction of the peripheral auditory nerve (AN) contributes to dynamic changes throughout the central auditory system, resulting in abnormal auditory processing, including hypersensitivity. Altered sound sensitivity is frequently observed in autism spectrum disorder (ASD), suggesting that AN deficits and changes in auditory information processing may contribute to ASD-associated symptoms, including social communication deficits and hyperacusis. The MEF2C transcription factor is associated with risk for several neurodevelopmental disorders, and mutations or deletions of MEF2C produce a haploinsufficiency syndrome characterized by ASD, language, and cognitive deficits. A mouse model of this syndromic ASD (Mef2c-Het) recapitulates many of the MEF2C haploinsufficiency syndrome-linked behaviors, including communication deficits. We show here that Mef2c-Het mice of both sexes exhibit functional impairment of the peripheral AN and a modest reduction in hearing sensitivity. We find that MEF2C is expressed during development in multiple AN and cochlear cell types; and in Mef2c-Het mice, we observe multiple cellular and molecular alterations associated with the AN, including abnormal myelination, neuronal degeneration, neuronal mitochondria dysfunction, and increased macrophage activation and cochlear inflammation. These results reveal the importance of MEF2C function in inner ear development and function and the engagement of immune cells and other non-neuronal cells, which suggests that microglia/macrophages and other non-neuronal cells might contribute, directly or indirectly, to AN dysfunction and ASD-related phenotypes. Finally, our study establishes a comprehensive approach for characterizing AN function at the physiological, cellular, and molecular levels in mice, which can be applied to animal models with a wide range of human auditory processing impairments.SIGNIFICANCE STATEMENT This is the first report of peripheral auditory nerve (AN) impairment in a mouse model of human MEF2C haploinsufficiency syndrome that has well-characterized ASD-related behaviors, including communication deficits, hyperactivity, repetitive behavior, and social deficits. We identify multiple underlying cellular, subcellular, and molecular abnormalities that may contribute to peripheral AN impairment. Our findings also highlight the important roles of immune cells (e.g., cochlear macrophages) and other non-neuronal elements (e.g., glial cells and cells in the stria vascularis) in auditory impairment in ASD. The methodological significance of the study is the establishment of a comprehensive approach for evaluating peripheral AN function and impact of peripheral AN deficits with minimal hearing loss.

Explicit and implicit attachment representations in cognitively able school-age children with autism spectrum disorder: A window to their inner world.

The few studies available on quality of attachment in school-age children with autism spectrum disorder (ASD) exclusively used questionnaires assessing explicit attachment representations. Thus, in the current study we assessed both explicit and implicit attachment representations in 23 children with ASD (without intellectual disability), 22 with learning disabilities and 27 with typical development aged from 7 to 13years. A self-reported measure on the quality of attachment to parents and a semi-structured interview were administered to the children. In addition, a developmental assessment of the child including measures of intelligence and social-communication impairment was conducted. Despite the lack of group differences on explicit attachment representations, we found that children with ASD showed higher rates of at-risk self-protective strategies and psychological trauma compared to the TD group. Children with SLD also showed a high level of at-risk implicit attachment representations than TD, albeit to a lesser extent compared to children with ASD. These results may be related to several factors associated with ASD impairment and developmental pathways, such as the atypical learning process which occur at interpersonal level, the difficulties in social information processing and reflective functioning. Our findings suggested that children with ASD may experience difficulties in the construction of balanced implicit attachment representations. Thus, a more comprehensive assessment of attachment including both implicit and explicit representations is recommended.