Testing Sensory and Multisensory Function in Children with Autism Spectrum Disorder

In addition to impairments in social communication and the presence of restricted interests and repetitive behaviors, deficits in sensory processing are now recognized as a core symptom in autism spectrum disorder (ASD). Our ability to perceive and interact with the external world is rooted in sensory processing. For example, listening to a conversation entails processing the auditory cues coming from the speaker (speech content, prosody, syntax) as well as the associated visual information (facial expressions, gestures). Collectively, the “integration” of these multisensory (i.e., combined audiovisual) pieces of information results in better comprehension. Such multisensory integration has been shown to be strongly dependent upon the temporal relationship of the paired stimuli. Thus, stimuli that occur in close temporal proximity are highly likely to result in behavioral and perceptual benefits – gains believed to be reflective of the perceptual system''s judgment of the likelihood that these two stimuli came from the same source. Changes in this temporal integration are expected to strongly alter perceptual processes, and are likely to diminish the ability to accurately perceive and interact with our world. Here, a battery of tasks designed to characterize various aspects of sensory and multisensory temporal processing in children with ASD is described. In addition to its utility in autism, this battery has great potential for characterizing changes in sensory function in other clinical populations, as well as being used to examine changes in these processes across the lifespan.     

The Use of Stem Cells to Study Autism Spectrum Disorder

Autism spectrum disorder (ASD) affects as many as 1 in 68 children and is said to be the fastest-growing serious developmental disability in the United States. There is currently no medical cure or diagnostic test for ASD. Furthermore, the U.S. Food and Drug Administration has yet to approve a single drug for the treatment of autism’s core symptoms. Despite numerous genome studies and the identification of hundreds of genes that may cause or predispose children to ASD, the pathways underlying the pathogenesis of idiopathic ASD still remain elusive. Post-mortem brain samples, apart from being difficult to obtain, offer little insight into a disorder that arises through the course of development. Furthermore, ASD is a disorder of highly complex, human-specific behaviors, making it difficult to model in animals. Stem cell models of ASD can be generated by performing skin biopsies of ASD patients and then dedifferentiating these fibroblasts into human-induced pluripotent stem cells (hiPSCs). iPSCs closely resemble embryonic stem cells and retain the unique genetic signature of the ASD patient from whom they were originally derived. Differentiation of these iPSCs into neurons essentially recapitulates the ASD patient’s neuronal development in a dish, allowing for a patient-specific model of ASD. Here we review our current understanding of the underlying neurobiology of ASD and how the use of stem cells can advance this understanding, possibly leading to new therapeutic avenues.     

孤独症谱系障碍的遗传基础与神经机制

孤独症谱系障碍(autism spectrum disorder,ASD)是一种神经精神障碍,主要表现为社会交往障碍、交流障碍以及局限性的兴趣和重复刻板的行为模式三个主要核心症状．本文介绍了ASD的遗传基础和神经机制的最新研究进展．ASD具有较高的遗传率,且ASD个体的5-羟色胺和睾丸激素都较高．神经影像学研究发现,ASD个体的杏仁核、扣带回、梭状回、镜像神经元和前额叶等大脑区域在结构和功能上都与正常发育个体存在差异,但在个别区域激活模式的差异方向上仍存在不一致的地方．此外,功能连接的研究结果也证实了ASD个体连接不良的假设．未来的研究应该更多地着眼于如何利用这些基础研究成果为临床上提出有效的治疗和训练方式．     

Time Domain Analysis of Heart Rate Variability Signals in Valence Recognition for Children with Autism Spectrum Disorder (ASD)

BackgroundAutism Spectrum Disorder (ASD) is a neurodevelopmental condition that is characterized by various social impairments. Children with ASD have major difficulties in expressing themselves, resulting in stress and meltdowns. Understanding their hidden feelings and needs may help in tackling and avoiding such strenuous behaviors.ObjectiveThis research aims to aid the parents and caretakers of children with ASD to understand the hidden and unexpressed emotional state by using physiological signals obtained from wearable devices.MethodsHere, electrocardiogram (ECG) signals pertaining to two valence states (‘like’ and ‘dislike’) were recorded from twenty children (10 Control and 10 children with ASD). The heart rate variability (HRV) signals were then obtained from the ECG signals using the Pan-Tompkins's algorithm. The statistical, higher order statistics (HOS) and geometrical features which were statistically significant were trained using the K Nearest Neighbor (KNN) and Ensemble Classifier algorithms.ResultsThe findings of our analysis indicate that the integration of major statistical features resulted in an overall average accuracy of 84.8% and 75.3% using HRV data for the control and test population, respectively. Similarly, geometrical features resulted in a maximum average accuracy of 84.8% and 74.2% for control and test population respectively. The decreased HRV in the test population indicates the presence of autonomic dysregulation in children with ASD when compared to their control peers.     

Toward Innovative,Cost-Effective,and Systemic Solutions to Improve Outcomes and Well-Being of Military Families Affected by Autism Spectrum Disorder

The burdens faced by military families who have a child with autism are unique. The usual challenges of securing diagnostic, treatment, and educational services are compounded by life circumstances that include the anxieties of war, frequent relocation and separation, and a demand structure that emphasizes mission readiness and service. Recently established military autism-specific health care benefits set the stage for community-viable and cost-effective solutions that can achieve better outcomes for children and greater well-being for families. Here we argue for implementation of evidence-based solutions focused on reducing age of diagnosis and improving access to early intervention, as well as establishment of a tiered menu of services, individualized to the child and family, that fit with the military ethos and system of health care. Absence of this new model of care could compromise the utility and sustainability of the autism-specific benefit.     

Pet Dogs Improve Family Functioning and Reduce Anxiety in Children with Autism Spectrum Disorder

ABSTRACT

There is increasing evidence to suggest that dogs are beneficial for children with Autism Spectrum Disorder (ASD) in therapy sessions, and anecdotal reports suggest that dogs may have wider benefits, in a family setting. This study investigated the effect of dog ownership on family functioning and child anxiety. Using a validated scale of family strengths and weaknesses (Brief Version of the Family Assessment Measure-III [General Scale]), we compared parents of children with ASD who had recently acquired a pet dog (n=42, Intervention group) with a similar group of parents not acquiring a dog (n=28, Control group) at matched time points. A sub-population (n =14 acquiring a dog, n=26 controls) completed a parental-report measure of child anxiety (Spence Children's Anxiety Scale). The primary carer completed the scales via telephone at Baseline (up to 17 weeks before acquiring a dog), Post-intervention (3–10 weeks after acquisition), and Follow-up (25–40 weeks after acquisition). Over time, scores for family functioning showed significant improvements (reduced family weaknesses, increased strengths) in the dog-owning compared with the non-dog owning group. In comparison with the non-dog owning group, anxiety scores in the dog-owning group reduced by a greater percentage, most notably in the domains of Obsessive Compulsive Disorder (26% greater decrease), Panic Attack and Agoraphobia (24%), Social Phobia (22%), and Separation Anxiety (22%). The results illustrate the potential of pet dogs to improve whole family functioning and child anxiety.     

谷氨酸-谷氨酰胺循环异常与孤独症谱系障碍研究进展

孤独症谱系障碍（autism spectrum disorder,ASD）是一种多病因神经发育性疾病,人群患病率高,病因复杂多样,包括炎症、自身免疫、基因异常等,但具体发病机制尚不清楚。在哺乳动物中枢神经系统（central nervous system,CNS）中,谷氨酸是最主要的兴奋性神经递质,也是一种潜在的神经毒素,其引起的兴奋毒性可能导致神经细胞的死亡。而星形胶质细胞和神经元之间谷氨酸-谷氨酰胺的代谢偶联,防止了过量的谷氨酸扩散到周围神经元上,进而避免了神经元的过度兴奋,对神经元起到保护作用。有研究表明,谷氨酸-谷氨酰胺循环异常可能为ASD发生的核心机制。因此,对炎症、自身免疫、基因异常等孤独症谱系障碍经典病因与谷氨酸-谷氨酰胺循环之间的联系进行综述,以期为孤独症谱系障碍分型和治疗提供一种新思路。     

Application of Human‐Induced Pluripotent Stem Cells (hiPSCs) to Study Synaptopathy of Neurodevelopmental Disorders

Synapses are the basic structural and functional units for information processing and storage in the brain. Their diverse properties and functions ultimately underlie the complexity of human behavior. Proper development and maintenance of synapses are essential for normal functioning of the nervous system. Disruption in synaptogenesis and the consequent alteration in synaptic function have been strongly implicated to cause neurodevelopmental disorders such as autism spectrum disorders (ASDs) and schizophrenia (SCZ). The introduction of human‐induced pluripotent stem cells (hiPSCs) provides a new path to elucidate disease mechanisms and potential therapies. In this review, we will discuss the advantages and limitations of using hiPSC‐derived neurons to study synaptic disorders. Many mutations in genes encoding for proteins that regulate synaptogenesis have been identified in patients with ASDs and SCZ. We use Methyl‐CpG binding protein 2 (MECP2), SH3 and multiple ankyrin repeat domains 3 (SHANK3) and Disrupted in schizophrenia 1 (DISC1) as examples to illustrate the promise of using hiPSCs as cellular models to elucidate the mechanisms underlying disease‐related synaptopathy.     

孤独症谱系障碍儿童早期神经发育水平和智能特征分析

目的:探讨孤独症谱系障碍(Autism spectrum disorder,ASD)儿童早期神经发育水平及智能分区特征,为提高ASD的早期识别和诊断提供理论依据.方法:运用Gesell发育评估量表对18月龄至48月龄以内的27例ASD患儿和30例发育迟缓(Mental retardation,MR)患儿的发育商(Dev...     

Assessment of Techniques for Teaching School Children with Autism

BackgroundIn the modern era, researchers are facing a big challenge in diagnosing autism disorders. According to the Center for Disease Control and Prevention 2014 report, the prevalence of autism among children in the United States is approximately 1 out of 88 children; whereas, in South Korea, the prevalence is 1 out of 38. In India, most of the children with autism are yet to be diagnosed partly due to the lack of self-screening test compared to the other countries. Currently, no data is available for analyzing the prevalence of autism in India. In order to improve the behavior, the social interaction, and the verbal communication of these children, scientists are using various kinds of teaching methods.ObjectivesThe objectives of this work were to screen the level of autism among school children using Gilliam Autism Rating Scale (GARS-2) questionnaire and evaluate the effects of various teaching methods on social behavior of school children with autism.Methods and resultsNinety children in the age group between 3 – 16 years from three schools (S1 – 30, S2 – 30 and S3 – 30) with autism are participated in this study. In S1, the autistic children are trained with horseback riding and yoga therapy; whereas in the S2, the children are trained with normal teaching using blackboard and in the S3, the children are trained with cue cards. The GARS-2 questionnaire was used for assessing the communication, the stereotype behavior and the social interaction with the help of parents or the caregivers.ConclusionResults of our study revealed that raw and the standard scores of stereotyped behaviors was notably (p<0.05) low in S1 school children when collated with the other two (S2 and S3) schools. Similarly, the raw and the standard score of communication, the socially interaction sub-score was notably (p<0.05) low for the children in S3 when collated with the children in the other two schools. The study concluded that the horseback riding, the yoga therapy and the cue cards-based teaching methods improve the stereotyped behavior, increase concentration power and also helps in maintaining the children's mind stability.     

Autism Crises: Music Therapeutic Practice & Research at the Social Care Centre Tloskov,Czech Republic. A Short Report

CSS Tloskov is a social pediatric care center and a leading institution in the Czech Republic. Sixty-five percent of its clients are diagnosed with autism spectrum disorder (ASD) and receive usually music therapy as a main constituent of individually designed pedagogical and therapeutic programs. In contrast to numerous music therapeutic concepts that are based on musical improvisation, the Tloskov model advocates a complex approach involving favorite songs, instrumental improvisation, and body-oriented modalities such as muscle relaxation and breathing techniques.

Clinical analyses allow us to distinguish typical psychiatric exacerbations in our ASD-clients. These “autistic crises” comprise an “onset phase,” a “gradation phase,” a “culmination phase,” and a “subsiding phase,” which can be partly controlled by music therapeutic interventions. On the basis of Grounded Theory we used qualitative methods to examine system compatibility between clinical data and the 4-phase autism crisis theory and to generate hypotheses about mechanisms of successful music therapy.

Outcomes involve five main principles: identification and avoidance of specific stimuli and cues that trigger autism crises; direct musical “sedation”; acquisition of music-behavioral skills to “auto-regulate” pathological developments; and a sort of music therapeutic emotional re-balancing and consolidation of an inner equilibrium. The “right moment” of intervention and adjustment of musical experiences within a narrow range of the client’s aesthetic-emotional intensity tolerance are critical to therapeutic outcomes. Possible music therapeutic contra-indications have to be taken into consideration.     

Marble Burying and Nestlet Shredding as Tests of Repetitive,Compulsive-like Behaviors in Mice

Obsessive-compulsive disorder (OCD) and autism spectrum disorders (ASD) are serious and debilitating psychiatric conditions and each constitutes a significant public health concern, particularly in children. Both of these conditions are highlighted by the repeated expression of meaningless behaviors. Individuals with OCD often show checking, frequent hand washing, and counting. Children with ASDs also engage in repetitive tapping, arm or hand flapping, and rocking. These behaviors can vary widely in intensity and frequency of expression. More intense forms of repetitive behaviors can even result in injury (e.g. excessive grooming, hand washing, and self-stimulation). These behaviors are therefore very disruptive and make normal social discourse difficult. Treatment options for repetitive behaviors in OCD and ASDs are somewhat limited and there is great interest in developing more effective therapies for each condition. Numerous animal models for evaluating compulsive-like behaviors have been developed over the past three decades. Perhaps the animal models with the greatest validity and ease of use are the marble burying test and the nestlet shredding test. Both tests take advantage of the fact that the target behaviors occur spontaneously in mice. In the marble burying test, 20 marbles are arrayed on the surface of clean bedding. The number of marbles buried in a 30 min session is scored by investigators blind to the treatment or status of the subjects. In the nestlet shredding test, a nestlet comprised of pulped cotton fiber is preweighed and placed on top of cage bedding and the amount of the nestlet remaining intact after a 30 min test session is determined. Presently, we describe protocols for and show movie documentation of marble burying and nestlet shredding. Both tests are easily and accurately scored and each is sensitive to small changes in the expression of compulsive-like behaviors that result from genetic manipulations, disease, or head injury.     

应用行为分析联合感觉统合训练对孤独症谱系障碍儿童行为、发育、睡眠障碍的影响

摘要 目的：评价应用行为分析（ABA）联合感觉统合训练对孤独症谱系障碍（ASD）儿童行为、发育以及睡眠障碍的影响。方法：选入我院2021年1月~2023年1月收治的ASD儿童62例,随机分为对照组和观察组,各31例。两组均予以ABA疗法,观察组在此基础上接受感觉统合训练。评价两组的行为、发育及睡眠情况等,并进行统计比较。结果：观察组治疗总有效率87.10%,显著高于对照组的61.29%（P＜0.05）;两组治疗后ABC和ATEC量表的各项得分及总分均较治疗前减少,而观察组减少幅度更大,与对照组差异显著（P＜0.05）;与治疗前比较,两组治疗后Gesell量表各项得分明显升高（P＜0.05）,而观察组升高幅度显著大于对照组（P＜0.05）;两组治疗前CSHQ的各项评分及总分无明显差异（P＞0.05）,而治疗后,与对照组相比,观察组CSHQ各项评分及总分均较低（P＜0.05）。结论：ABA疗法联合感觉统合训练能够减轻ASD患儿的疾病症状,改善行为状态及睡眠质量,促进患儿发育,提高临床疗效。     

Focus: Health Equity: Factors Influencing the Relationship Between Work-Related Stress and Posttraumatic Stress Disorder Among Working Black Adults in the United States

Introduction: Work-related stress (WRS) and posttraumatic disorder (PTSD) is higher among Black adults relative to their White counterparts. Trauma exposure is not the only connection to increased risk for PTSD as WRS is highly associated with risk for PTSD. However, the factors that link WRS and PTSD among working Black adults is not well understood. Materials and Methods: Cross-sectional data from the National Survey of American Life was used to examine the relationship between WRS and PTSD among 2,139 working Black adults and to determine whether there are influencing factors. Results: Logistic regression analyses revealed that working Black adults who reported experiencing WRS was associated with higher odds of PTSD than those who reported no WRS (OR: 1.24, 95% CI: 1.04-1.48). The relationship was attenuated when depression, alcohol abuse, and major discrimination were added to the model (OR: 1.09, 95% CI: 0.87-1.36). Mediation analyses show that the average indirect effect of WRS on PTSD were 0.09 ± 0.04 for alcohol abuse, 0.14 ± 0.06 for depression, and 0.35 ± 0.10 for major discrimination. Conclusion: The results underscore the need for culturally responsive trauma-informed public health interventions for working Black adults. Public health practitioners should be alerted to the relationship between WRS and PTSD among working Black adults and the potential contributing factors (alcohol abuse, depression, and major discrimination). Special attention should be given to working Black females with their worse PTSD status and major discrimination experiences which demonstrated greater effect on the relationship between WRS and PTSD.     

A generalized weighted quantile sum approach for analyzing correlated data in the presence of interactions

A weighted quantile sum (WQS) regression has been used to assess the associations between environmental exposures and health outcomes. However, the currently available WQS approach, which is based on additive effects, does not allow exploring for potential interactions of exposures with other covariates in relation to a health outcome. In addition, the current WQS cannot account for clustering, thus it may not be valid for analysis of clustered data. We propose a generalized WQS approach that can assess interactions by estimating stratum‐specific weights of exposures in a mixture, while accounting for potential clustering effect of matched pairs of cases and controls as well as censored exposure data due to being below the limits of detection. The performance of the proposed method in identifying interactions is evaluated through simulations based on various scenarios of correlation structures among the exposures and with an outcome. We also assess how well the proposed method performs in the presence of the varying levels of censoring in exposures. Our findings from the simulation study show that the proposed method outperforms the traditional WQS, as indicated by higher power of detecting interactions. We also find no strong evidence that the proposed method falsely identifies interactions when there are no true interactive effects. We demonstrate application of the proposed method to real data from the Epidemiological Research on Autism Spectrum Disorder (ASD) in Jamaica (ERAJ) by examining interactions between exposure to manganese and glutathione S‐transferase family gene, GSTP1 in relation to ASD.     

孤独症谱系障碍儿童听觉脑干反应特征分析

摘要 目的：探讨孤独症谱系障碍(autism spectrum disorder,ASD)儿童听觉脑干反应(auditory brainstem response,ABR)各波潜伏期和波间期特征与ASD行为表型间的关联。方法：对2019年7月-2020年12月来我科就诊的26例明确诊断的2~6岁ASD儿童的患儿进行声导抗,听性脑干反应,畸变产物耳声发射及多频稳态听觉诱发电位测试,以38例正常儿童为对照组,进行同样的测试,并对其测试结果进行统计分析。分析ASD儿童左右耳各波潜伏期,波间期特征及与ASD临床表型的关联。结果：ASD儿童左右耳Ⅰ,Ⅲ,Ⅴ波潜伏期分别为(1.42±0.09)ms,(3.67±0.09)ms,(5.65±0.13)ms;(1.45±0.11)ms,(3.69±0.08)ms,(5.62±0.15)ms。ASD组的右耳I,III波的潜伏期均值大于正常组 (P 值均＜0.05);ASD儿童两组间左耳III-V,右耳III-V,右耳I-V的波间期分别是(1.97±0.07)ms,(1.93±0.10)ms,(4.15±0.14)ms;ASD组的左耳III-V,右耳III-V,右耳I-V波间期均小于正常组(P 值均＜0.05);ASD组中小于等于3岁组与大于3岁组间ABR波间期差异不具有统计学意义。关联性分析发现,ASD儿童语言能力与右耳III波潜伏期,右耳最小阈值V波潜伏期负相关;社会行为能力与右耳I-III波间期负相关;社会生活能力与左耳最小阈值V波潜伏期负相关;而ABC评分与ASD儿童右耳III波潜伏期,左耳I-III波间期,右耳I-III波间期正相关。结论：ASD儿童存在异常的听觉脑干反应特征,且异常程度与 ASD 儿童语言,社会行为能力,社会生活能力的严重程度存在明显关联。