Enhanced brain signal variability in children with autism spectrum disorder during early childhood

Extensive evidence shows that a core neurobiological mechanism of autism spectrum disorder (ASD) involves aberrant neural connectivity. Recent advances in the investigation of brain signal variability have yielded important information about neural network mechanisms. That information has been applied fruitfully to the assessment of aging and mental disorders. Multiscale entropy (MSE) analysis can characterize the complexity inherent in brain signal dynamics over multiple temporal scales in the dynamics of neural networks. For this investigation, we sought to characterize the magnetoencephalography (MEG) signal variability during free watching of videos without sound using MSE in 43 children with ASD and 72 typically developing controls (TD), emphasizing early childhood to older childhood: a critical period of neural network maturation. Results revealed an age‐related increase of brain signal variability in a specific timescale in TD children, whereas atypical age‐related alteration was observed in the ASD group. Additionally, enhanced brain signal variability was observed in children with ASD, and was confirmed particularly for younger children. In the ASD group, symptom severity was associated region‐specifically and timescale‐specifically with reduced brain signal variability. These results agree well with a recently reported theory of increased brain signal variability during development and aberrant neural connectivity in ASD, especially during early childhood. Results of this study suggest that MSE analytic method might serve as a useful approach for characterizing neurophysiological mechanisms of typical‐developing and its alterations in ASD through the detection of MEG signal variability at multiple timescales. Hum Brain Mapp 37:1038–1050, 2016. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc .     

Predicting child PTSD: the relationship between acute stress disorder and PTSD in injured children

OBJECTIVE: To examine the prevalence of acute stress disorder (ASD) and posttraumatic stress disorder (PTSD) in injured children and to evaluate the utility of ASD as a predictor of PTSD. METHOD: Children hospitalized for injuries sustained in a traffic crash were enrolled in a prospective study. ASD was assessed in 243 children within 1 month after injury, and PTSD was assessed in 177 of these children 3 or more months after injury. The relationship between ASD and PTSD was examined via correlations between symptom severity scores and calculation of sensitivity, specificity, and positive and negative predictive values for categorical prediction of PTSD from ASD or subsets of ASD symptoms. RESULTS: Eight percent of children met the symptom criteria for ASD and another 14% had subsyndromal ASD; 6% met the symptom criteria for PTSD and another 11% had subsyndromal PTSD. ASD and PTSD symptom severity were associated. Sensitivity was low for prediction of child PTSD from child ASD. Subsyndromal ASD was a more effective predictor of PTSD. CONCLUSIONS: A substantial minority of injured children are affected by traumatic stress disorders. ASD in children may not be an optimal categorical predictor of PTSD. With increasing attention to early posttrauma services for children, empirically valid assessment/triage models deserve further study.     

Altered inter‐ and intrahemispheric functional connectivity dynamics in autistic children

Emerging evidence has associated autism spectrum disorder (ASD) with static functional connectivity abnormalities between multiple brain regions. However, the temporal dynamics of intra‐ and interhemispheric functional connectivity patterns remain unknown in ASD. Resting‐state functional magnetic resonance imaging data were analyzed for 105 ASD and 102 demographically matched typically developing control (TC) children (age range: 7–12 years) available from the Autism Brain Imaging Data Exchange database. Whole‐brain functional connectivity was decomposed into ipsilateral and contralateral functional connectivity, and sliding‐window analysis was utilized to capture the intra‐ and interhemispheric dynamic functional connectivity density (dFCD) patterns. The temporal variability of the functional connectivity dynamics was further quantified using the standard deviation (SD) of intra‐ and interhemispheric dFCD across time. Finally, a support vector regression model was constructed to assess the relationship between abnormal dFCD variance and autism symptom severity. Both intra‐ and interhemispheric comparisons showed increased dFCD variability in the anterior cingulate cortex/medial prefrontal cortex and decreased variability in the fusiform gyrus/inferior temporal gyrus in autistic children compared with TC children. Autistic children additionally showed lower intrahemispheric dFCD variability in sensorimotor regions including the precentral/postcentral gyrus. Moreover, aberrant temporal variability of the contralateral dFCD predicted the severity of social communication impairments in autistic children. These findings demonstrate altered temporal dynamics of the intra‐ and interhemispheric functional connectivity in brain regions incorporating social brain network of ASD, and highlight the potential role of abnormal interhemispheric communication dynamics in neural substrates underlying impaired social processing in ASD.     

Network connectivity abnormality profile supports a categorical‐dimensional hybrid model of ADHD

Attention‐deficit/hyperactivity disorder (ADHD) is characterized by inattention, hyperactivity, and impulsivity, but there is no consensus regarding whether ADHD exists on the extreme end of a continuum of normal behavior or represents a discrete disorder. In this study, we sought to characterize both the categorical and dimensional variations in network functional connectivity in order to identify neural connectivity mechanisms of ADHD. Functional connectivity analyses of resting‐state fMRI data from 155 children with ADHD and 145 typically developing children (TDC) defined the dorsal attention network (DA), default mode network (DM), salience processing network (SAL) and executive control network (CON). Regional alterations in connectivity associated with categorical diagnoses and dimensional symptom measures (inattention and hyperactivity/impulsivity) as well as their interaction were systematically characterized. Dimensional relationships between symptom severity measures and functional connectivity that did not differ between TDC and children with ADHD were observed for each network, supporting a dimensional characterization of ADHD. However, categorical differences in functional connectivity magnitude between TDC and children with ADHD were detected after accounting for dimensional relationships, indicating the existence of categorical mechanisms independent of dimensional effects. Additionally, differential dimensional relationships for TDC versus ADHD children demonstrated categorical differences in brain–behavior relationships. The patterns of network functional organization associated with categorical versus dimensional measures of ADHD accentuate the complexity of this disorder and support a dual characterization of ADHD etiology featuring both dimensional and categorical mechanisms. Hum Brain Mapp 35:4531–4543, 2014. © 2014 Wiley Periodicals, Inc .     

Differential dysfunctions related to alcohol and cannabis use disorder symptoms in reward and error-processing neuro-circuitries in adolescents

Alcohol and cannabis are two of the most commonly used substances by adolescents and are associated with adverse medical and psychiatric outcomes. These adverse psychiatric outcomes may reflect the negative impact of alcohol and/or cannabis abuse on neural systems mediating reward and/or error detection. However, work indicative of this has mostly been conducted in adults with Alcohol and/or Cannabis Use Disorder (i.e., AUD and CUD), with relatively little work in adolescent patients. Furthermore, of the work that has been conducted in adolescents, groups were based on categorical diagnoses of AUD and/or CUD, so the relationship between AUD and/or CUD symptom severity in adolescents and neural dysfunction is unclear. We used a Monetary Incentive Delay (MID) task to examine the relationship between AUDIT and/or CUDIT scores and functional integrity of neuro-circuitries mediating reward processing and error detection within 150 adolescents. Our findings indicate that AUDIT score is negatively related to activity in reward processing neuro-circuitry in adolescents. However, CUDIT score is negatively related to activity in brain regions involved in error detection. Each of these relationships reflected a medium effect size (Partial-η² 0.09-0.14). These data suggest differential impacts of AUD and CUD on reward versus error detection neuro-circuitries within the adolescent brain.     

Salivary cortisol levels and challenging behavior in children with autism spectrum disorder

A relationship between stress and challenging behavior in individuals with autism spectrum disorder (ASD) has been theorized but infrequently examined empirically. The current study sought to examine the relationship between a parent-reported measure of stress, a physiological measure of stress (diurnal salivary cortisol), and various topographies of challenging behavior among 61 children and adolescents diagnosed with ASD between the ages of three and 18 years. Significant differences in cortisol levels between those engaging in high and low rates of stereotyped behavior were observed such that higher levels of stereotypy appeared an overt manifestation of higher levels of stress. A comparison between a subset of participants with ASD and typically developing peers matched on age, gender, and pubertal status failed to yield any differences in diurnal cortisol levels or cortisol variability between the two groups. The results of the current study suggest that similar levels of stress may exist among children with autism and their typically developing peers, but that for a subset of individuals with ASD, stereotyped behavior may be an indicator of elevated cortisol levels.     

Atypical auditory language processing in adolescents with autism spectrum disorder

Objective

Individuals with autism spectrum disorder (ASD) often show characteristic differences in auditory processing. To clarify the mechanisms underlying communication impairment in ASD, we examined auditory language processing with both anatomical and functional methods.

改进排列熵方法及其在心率变异复杂度分析中的应用*☆◆

背景：心率变异信号蕴含着有关心血管系统调节的重要信息,很多非线性动力学方法和复杂性测度已被用于心率变异信号的分析。排列熵是近年提出的一种新的熵测度,具有概念简单,计算简洁等优点,在很多领域得到了广泛的应用。 目的：针对心率变异信号特点,对排列熵方法进行等值状态处理的改进,在排列符号序列中以相同符号代表等值状态;通过临床数据实验,考察改进排列熵方法在心率变异性信号分析中的应用价值。 方法：心率变异信号取自PhysioNet中MIT-BIH Fantasia数据库和BIDMC Congestive Heart Failure(CHF)数据库,分为年轻健康人、老年健康人和充血性心力衰竭患者3组。应用排列熵和改进排列熵方法对3组数据分别进行分析,通过单因素方差分析和t检验对结果进行统计分析。 结果与结论：排列熵的两种等值状态处理方法均无法对3组数据作出有效区分,尤其是年轻健康人和老年健康人两组数据;而改进排列熵方法可以对3组数据作出非常有效的区分,即使是在短时的心率变异性分析中(500个RR间期,6~7 min)。提示改进排列熵方法可以有效提高生理、病理心率变异信号的区分度,比排列熵方法更有效的表征心率变异信号的复杂性。     

DSM-V and the future diagnosis of attention-deficit/hyperactivity disorder

In general, recommendations for the DSM-V and future diagnoses of psychiatric disorders include a dimensional approach to complement the standard categorical approach. For the assessment of attention-deficit/hyperactivity disorder (ADHD), dimensional approaches to supplement the rigid categorical approach of the DSM-IV abound. Historically, dimensions based on severity of symptoms of ADHD and severity of general psychopathology have been used. General dimensional approaches described by a workgroup organized by the American Psychiatric Association are reviewed to provide background and context for a discussion of old and new dimensional approaches to complement future categorical diagnosis of ADHD in the DSM-V.     

Touch Processing and Social Behavior in ASD

Abnormal patterns of touch processing have been linked to core symptoms in ASD. This study examined the relation between tactile processing patterns and social problems in 44 children and adolescents with ASD, aged 6–14 (M?=?8.39?±?2.35). Multiple linear regression indicated significant associations between touch processing and social problems. No such relationships were found for social problems and autism severity. Within touch processing, patterns of hyper-responsiveness and hypo-responsiveness best predicted social problems, whereas sensory-seeking did not. These results support that atypical touch processing in individuals with ASD might be contributing to the social problems they present. Moreover, it the need to explore more in depth the contribution of sensory features to the ASD phenotype.     

Intact hedonic responses to sweet tastes in autism spectrum disorder

The Sweet Taste Test (STT) is a standardized measure designed to index the ability to detect differences in sweet tastes (sweet taste sensitivity) and hedonic responses to sweet tastes (sweet taste liking). Profiles of response on the STT suggest enhanced hedonic responses to sweet tastes in psychiatric disorders characterized by dysfunctional reward processing systems, including binge-eating disorders and substance use disorders, and a putative mechanism governing STT responses is the brain opioid system. The present study examined STT responses in 20 adults with autism spectrum disorder (ASD) and 38 healthy control adults. There were no differences in sweet taste sensitivity or hedonic response to sweet tastes between the ASD and control groups. Within the ASD sample, ASD symptom severity was associated with sweet taste sensitivity, but not hedonic response to sweet taste. Results may ultimately shed light on brain opioid system functioning in ASD.     

Managing Complexity: Impact of Organization and Processing Style on Nonverbal Memory in Autism Spectrum Disorders

The contributions of cognitive style and organization to processing and recalling a complex novel stimulus were examined by comparing the Rey Osterrieth Complex Figure (ROCF) test performance of children, adolescents, and adults with ASD to clinical controls (CC) and non-impaired controls (NC) using the Developmental Scoring System. The ROCF task involves a complex structure with strong organizational or integrative processing demands. The individuals with ASD relied on a predominantly part-oriented strategy to cope with the complexity of the task and did not make the typical developmental shift to a configurational approach. Both processing style and organization (whether pieces of information were perceived as connected to one another in a meaningful way) contributed to structural recall in the ASD group.     

Friendship and Internalizing Symptoms Among Children and Adolescents with ASD

Anxiety and depression are common among children and adolescents with autism spectrum disorders (ASD), highlighting a need to identify factors that protect against these symptoms. Among typically developing children, friendships are protective, and lead to better emotional outcomes. The current study examined a large, well-characterized sample of children and adolescents with ASD to examine the relations among friendship, ASD symptom severity, and anxiety/depression. Rates of anxiety/depression were high in this sample. Greater ASD severity was associated with fewer symptoms of anxiety/depression, lower IQ, and poorer number and/or quality of reciprocal friendships. Surprisingly, children with no or very poor dyadic relationships experienced less anxiety than those with existing, but limited, friendships. Implications and directions for future research are discussed.     

Visual search in ADHD,ASD and ASD + ADHD: overlapping or dissociating disorders?

Recent debates in the literature discuss commonalities between Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) at multiple levels of putative causal networks. This debate requires systematic comparisons between these disorders that have been studied in isolation in the past, employing potential markers of each disorder to be investigated in tandem. The present study, choose superior local processing, typical to ASD, and increased Intra-Subject Variability (ISV), typical to ADHD, for a head-to-head comparison of the two disorders, while also considering the comorbid cases. It directly examined groups of participants aged 10–13 years with ADHD, ASD with (ASD+) or without (ASD−) comorbid ADHD and a typically developing (TD) group (total N = 85). A visual search task consisting of an array of paired words was designed. The participants needed to find the specific pair of words, where the first word in the pair was the cue word. This visual search task was selected to compare these groups on overall search performance and trial-to-trial variability of search performance (i.e., ISV). Additionally, scanpath analysis was also carried out using Recurrence Quantification Analysis (RQA) and the Multi-Match Model. Results show that only the ASD− group exhibited superior search performance; whereas, only the groups with ADHD symptoms showed increased ISV. These findings point towards a double dissociation between ASD and ADHD, and argue against an overlap between ASD and ADHD.

     

Affective problems,gastrointestinal symptoms,sleep problems,and challenging behaviour in children and adolescents with autism spectrum disorder

BackgroundPeople with autism spectrum disorder (ASD) can experience affective problems, gastrointestinal (GI) symptoms, sleep problems, and challenging behaviour. This study identified the frequency of affective problems and explored how they related to co-occurring conditions in children and adolescents with ASD.MethodParticipants were children and adolescents diagnosed with ASD using DSM-IV-TR criteria (n = 95), 40 % (n = 38) of whom also had a diagnosis of intellectual disability (ID). The following scales were completed by the participants’ parents or guardians: Child Behaviour Checklist (CBCL), Gastrointestinal Symptoms Inventory, Children’s Sleep Habits Questionnaire (CSHQ), and the Behaviour Problems Inventory-Short Form (BPI-S). Pearson’s correlations and independent sample t-tests were used to examine the relationships between variables. Two hierarchal multiple regressions examined predictors for affective problems in preschool and school-aged children with ASD.ResultsParticipants scored in the clinical range (69.5 %) and borderline range (10.5 %) for affective problems. Significant positive relationships were found between affective problems and sleep problems, GI symptoms, and challenging behaviour. ID and gender predicted affective problems in preschool aged children. In school-aged children, affective problems were predicted by ID, sleep problems, and aggressive/destructive behaviour severity. However, only 25 % of the variance in affective problems was accounted for.ConclusionsFuture research is needed to understand how affective problems are impacted by co-occurring conditions in children and adolescents with ASD. Affective problems are prevalent in this population and the quality of life for individuals may be improved if practitioners consider co-occurring conditions during clinical practice.     

Maturational trajectories of local and long‐range functional connectivity in autism during face processing

Autism spectrum disorder (ASD) is characterized neurophysiologically by, among other things, functional connectivity abnormalities in the brain. Recent evidence suggests that the nature of these functional connectivity abnormalities might not be uniform throughout maturation. Comparing between adolescents and young adults (ages 14–21) with ASD and age‐ and IQ‐matched typically developing (TD) individuals, we previously documented, using magnetoencephalography (MEG) data, that local functional connectivity in the fusiform face areas (FFA) and long‐range functional connectivity between FFA and three higher order cortical areas were all reduced in ASD. Given the findings on abnormal maturation trajectories in ASD, we tested whether these results extend to preadolescent children (ages 7–13). We found that both local and long‐range functional connectivity were in fact normal in this younger age group in ASD. Combining the two age groups, we found that local and long‐range functional connectivity measures were positively correlated with age in TD, but negatively correlated with age in ASD. Last, we showed that local functional connectivity was the primary feature in predicting age in ASD group, but not in the TD group. Furthermore, local functional connectivity was only correlated with ASD severity in the older group. These results suggest that the direction of maturation of functional connectivity for processing of faces from childhood to young adulthood is itself abnormal in ASD, and that during the processing of faces, these trajectory abnormalities are more pronounced for local functional connectivity measures than they are for long‐range functional connectivity measures.     

The scope of social attention deficits in autism: Prioritized orienting to people and animals in static natural scenes

A central feature of autism spectrum disorder (ASD) is an impairment in ‘social attention’—the prioritized processing of socially relevant information, e.g. the eyes and face. Socially relevant stimuli are also preferentially attended in a broader categorical sense, however: observers orient preferentially to people and animals (compared to inanimate objects) in complex natural scenes. To measure the scope of social attention deficits in autism, observers viewed alternating versions of a natural scene on each trial, and had to ‘spot the difference’ between them—where the difference involved either an animate or inanimate object. Change detection performance was measured as an index of attentional prioritization. Individuals with ASD showed the same prioritized social attention for animate categories as did control participants. This could not be explained by lower level visual factors, since the effects disappeared when using blurred or inverted images. These results suggest that social attention - and its impairment in autism - may not be a unitary phenomenon: impairments in visual processing of specific social cues may occur despite intact categorical prioritization of social agents.     

高功能孤独症谱系障碍儿童青少年全脑白质结构网络的研究

目的:对比分析高功能孤独症谱系障碍(ASD)儿童青少年患者的全脑白质结构网络的拓扑属性特征。方法:对36例6~16岁高功能ASD患者以及39例年龄、性别以及智商相匹配的正常发育儿童对照组(TD组)进行弥散张量成像(DTI)扫描,在纤维追踪技术的基础上运用基于图论的分析方法分析两组被试脑网络的拓扑属性值,并进一步探讨高功能ASD儿童青少年脑网络拓扑属性特征值与年龄以及临床症状之间的相关性。结果:与TD组相比,高功能ASD儿童青少年脑结构网络的全局拓扑属性异常,表现为局部效率(Eloc)(P=0.02)和校正集群系数(γ)的显著降低(P=0.00)。结论:儿童青少年期高功能ASD全脑白质结构网络存在着小世界属性;与TD组相比,高功能ASD组全脑局部信息处理效率降低。     

Emotion Dysregulation and the Core Features of Autism Spectrum Disorder

The aim of this study was to examine the relationship between emotion dysregulation and the core features of Autism Spectrum Disorder (ASD), which include social/communication deficits, restricted/repetitive behaviors, and sensory abnormalities. An 18-item Emotion Dysregulation Index was developed on the basis of expert ratings of the Child Behavior Checklist. Compared to typically developing controls, children and adolescents with ASD showed more emotion dysregulation and had significantly greater symptom severity on all scales. Within ASD participants, emotion dysregulation was related to all core features of the disorder, but the strongest association was with repetitive behaviors. These findings may facilitate the development of more effective therapeutic strategies targeting emotion dysregulation in order to optimize long-term outcomes for individuals with ASD.     

Parsing brain structural heterogeneity in males with autism spectrum disorder reveals distinct clinical subtypes

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with considerable neuroanatomical heterogeneity. Thus, how and to what extent the brains of individuals with ASD differ from each other is still unclear. In this study, brain structural MRI data from 356 right‐handed, male subjects with ASD and 403 right‐handed male healthy controls were selected from the Autism Brain Image Data Exchange database (age range 5–35 years old). Voxel‐based morphometry preprocessing steps were conducted to compute the gray matter volume maps for each subject. Individual neuroanatomical difference patterns for each ASD individual were calculated. A data‐driven clustering method was next utilized to stratify individuals with ASD into several subtypes. Whole‐brain functional connectivity and clinical severity were compared among individuals within the ASD subtypes identified. A searchlight analysis was applied to determine whether subtyping ASD could improve the classification accuracy between ASD and healthy controls. Three ASD subtypes with distinct neuroanatomical difference patterns were revealed. Different degrees of clinical severity and atypical brain functional connectivity patterns were observed among these three subtypes. By dividing ASD into three subtypes, the classification accuracy between subjects of two out of the three subtypes and healthy controls was improved. The current study confirms that ASD is not a disorder with a uniform neuroanatomical signature. Understanding neuroanatomical heterogeneity in ASD could help to explain divergent patterns of clinical severity and outcomes.