Automated Video Tracking of Autistic Children's Movement During Caregiver-Child Interaction: An Exploratory Study.

Objective, quantitative measures of caregiver-child interaction during play are needed to complement caregiver or examiner ratings for clinical assessment and tracking intervention responses. In this exploratory study, we examined the feasibility of using automated video tracking, Noldus EthoVision XT, to measure 159 2-to-7-year-old autistic children's patterns of movement during play-based, caregiver-child interactions and examined their associations with standard clinical measures and human observational coding of caregiver-child joint engagement. Results revealed that autistic children who exhibited higher durations and velocity of movement were, on average, younger, had lower cognitive abilities, greater autism-related features, spent less time attending to the caregiver, and showed lower levels of joint engagement. After adjusting for age and nonverbal cognitive abilities, we found that children who remained in close proximity to their caregiver were more likely to engage in joint engagement that required support from the caregiver. These findings suggest that video tracking offers promise as a scalable, quantitative, and relevant measure of autism-related behaviors.

Automated movement tracking of young autistic children during free play is correlated with clinical features associated with autism.

LAY ABSTRACT: Play-based observations allow researchers to observe autistic children across a wide range of ages and skills. We recorded autistic children playing with toys in the center of a room and at a corner table while a caregiver remained seated off to the side and used video tracking technology to track children's movement and location. We examined how time children spent in room regions and whether or not they approached each region during play related to their cognitive, social, communication, and adaptive skills to determine if tracking child movement and location can meaningfully demonstrate clinical variation among autistic children representing a range of ages and skills. One significant finding was that autistic children who spent more time in the toy-containing center of the room had higher cognitive and language abilities, whereas those who spent less time in the center had higher levels of autism-related behaviors. In contrast, children who spent more time in the caregiver region had lower daily living skills and those who were quicker to approach the caregiver had lower adaptive behavior and language skills. These findings support the use of movement tracking as a complementary method of measuring clinical differences among autistic children. Furthermore, over 90% of autistic children representing a range of ages and skills in this study provided analyzable play observation data, demonstrating that this method allows autistic children of all levels of support needs to participate in research and demonstrate their social, communication, and attention skills without wearing any devices.

Eye-tracking measures of social versus nonsocial attention are related to level of social engagement during naturalistic caregiver-child interactions in autistic children.

Eye-tracking (ET) measures indexing social attention have been proposed as sensitive measures related to autism, but less is known about the relationship between social and nonsocial attention and naturalistic measures of social engagement and whether sex moderates this relationship. This study investigated ET measures of social attention as predictors of social engagement during a naturalistic caregiver-child interaction (CCI). Participants included 132, 2-7-year-old autistic children (77% male) and their caregivers. Participants engaged in a CCI and an ET task in which they viewed a video of an actor making dyadic bids toward the child with toys in the background. Pearson correlations and multiple regression analyzes revealed that ET measures correlated with social engagement behaviors, including degree of attention to the caregiver and objects, joint engagement with the caregiver, and language-based joint engagement. Children who spent more time looking at toys were more likely to be unengaged during social interaction. Those who spent more time looking at the actor's mouth were more likely to engage in coordinated play with and without language. Sex moderated the relationship between time looking at toys and unengagement during play; males who spent more time looking at toys spent more time unengaged during play, whereas females who spent more time looking at toys spent less time unengaged during play. Overall, ET measures of social and nonsocial attention correlated with the level of social engagement during naturalistic play, with some sex differences. Eye-tracking measures that predict interaction patterns may provide insight into promoting social engagement between caregivers and their autistic children and can inform outcome monitoring and intervention development.

Associations between executive function and attention abilities and language and social communication skills in young autistic children.

LAY ABSTRACT: Executive functioning describes a set of cognitive processes that affect thinking and behavior. Past research has shown that autistic individuals often have delays in the acquisition of executive function abilities. Our study explored how differences in executive function and attention abilities relate to social abilities and communication/language in 180 young autistic children. Data were gathered via caregiver report (questionnaires/interviews) and an assessment of vocabulary skills. The ability to sustain attention to a dynamic video was measured via eye tracking. We found that children with higher levels of executive function skills demonstrated lower levels of social pragmatic problems, a measure of having difficulties in social contexts. Furthermore, children who were able to sustain their attention longer to the video displayed higher levels of expressive language. Our results emphasize the importance of executive function and attention skills across multiple areas of functioning in autistic children, in particular those that involve language and social communication.

Inequities in Receipt of the North Carolina Medicaid Waiver Among Individuals with Intellectual Disability or Autism Spectrum Disorder.

OBJECTIVE: We examined characteristics associated with receiving the North Carolina Home and Community-Based Services Waiver for intellectual and developmental disabilities (I/DDs) and its association with emergency department (ED) utilization. METHOD: Through analysis of the North Carolina 2017 to 2018 Medicaid claims and enrollment data, we examined characteristics (age, sex, race and ethnicity, geography, diagnosis (intellectual disability [ID] with or without autism spectrum disorders or autism spectrum disorder without ID) associated with receiving the NC I/DD Waiver and the association of this Wavier with ED utilization. We identified patients with at least 1 International Classification of Diseases-10-CM diagnosis code for an ID or autism spectrum disorder. We excluded patients with missing county information and whose enrollment in the NC I/DD Waiver program began after October 1, 2017. RESULTS: Only 22% of 53,531 individuals with I/DD in North Carolina received the Waiver. Non-Hispanic Blacks and Hispanic individuals were less likely to receive the Waiver than non-Hispanic White individuals. Adults (>21 years old), men, and urban residents were more likely to receive the Waiver. Individuals who received the Waiver were 31% less likely to use the ED. CONCLUSION: Innovative strategies are needed to provide equitable access to the NC I/DD Waiver and provide services to the 14,000 people with I/DD currently waiting to receive the Waiver. Through the Waiver, those with I/DD can access preventative and therapeutic outpatient services and decrease their need for ED care. These findings highlight the need for policy reform to address inequities in access to the Waiver for individuals with I/DD.

Pragmatic adaptations of telehealth-delivered caregiver coaching for children with autism in the context of COVID-19: Perspectives from the United States and South Africa.

LAY ABSTRACT: COVID-19 caused many autism spectrum disorder caregiver-coaching studies to move to telehealth. Telehealth can increase the diversity of people who take part in research. This matters because most autism spectrum disorder studies have included people who have resources, are White, and live in North America and Europe. When study participants are similar, it is hard to understand which interventions can help different types of people who live in different parts of the world. While telehealth may allow more people to take part in research, it needs to "fit" the local context and consider the "digital divide" because many people around the world have no access to computers and the Internet. This short report describes changes to two research studies that include caregiver coaching based on the Early Start Denver Model in the United States and South Africa. We describe how the local context, including technology and Internet access, guided the telehealth approach. By doing so, we highlight ways to make telehealth available to more people around the world. The pandemic can help us understand how telehealth can "fit" diverse places and support high-quality research. It is important that study changes are tracked and we assess how well the changes work. COVID-19 telehealth changes to caregiver coaching can result in new ways to reach more people around the world.

Shorter average look durations to dynamic social stimuli are associated with higher levels of autism symptoms in young autistic children.

LAY ABSTRACT: Many studies of autism look at the differences in how autistic research participants look at certain types of images. These studies often focus on where research participants are looking within the image, but that does not tell us everything about how much they are paying attention. It could be useful to know more about how well autistic research participants can focus on an image with people in it, because those who can look at images of people for longer duration without stopping may be able to easily learn other skills that help them to interact with people. We measured how long autistic research participants watched the video without breaking their attention. The video sometimes had a person speaking, and at other times had toys moving and making sounds. We measured the typical amount of time autistic research participants could look at the video before they looked away. We found that research participants with more severe autism tended to look at the video for shorter amounts of time. The ability to focus without stopping may be related to social skills in autistic people.

Computational Methods to Measure Patterns of Gaze in Toddlers With Autism Spectrum Disorder.

Importance: Atypical eye gaze is an early-emerging symptom of autism spectrum disorder (ASD) and holds promise for autism screening. Current eye-tracking methods are expensive and require special equipment and calibration. There is a need for scalable, feasible methods for measuring eye gaze. Objective: Using computational methods based on computer vision analysis, we evaluated whether an app deployed on an iPhone or iPad that displayed strategically designed brief movies could elicit and quantify differences in eye-gaze patterns of toddlers with ASD vs typical development. Design, Setting, and Participants: A prospective study in pediatric primary care clinics was conducted from December 2018 to March 2020, comparing toddlers with and without ASD. Caregivers of 1564 toddlers were invited to participate during a well-child visit. A total of 993 toddlers (63%) completed study measures. Enrollment criteria were aged 16 to 38 months, healthy, English- or Spanish-speaking caregiver, and toddler able to sit and view the app. Participants were screened with the Modified Checklist for Autism in Toddlers-Revised With Follow-up during routine care. Children were referred by their pediatrician for diagnostic evaluation based on results of the checklist or if the caregiver or pediatrician was concerned. Forty toddlers subsequently were diagnosed with ASD. Exposures: A mobile app displayed on a smartphone or tablet. Main Outcomes and Measures: Computer vision analysis quantified eye-gaze patterns elicited by the app, which were compared between toddlers with ASD vs typical development. Results: Mean age of the sample was 21.1 months (range, 17.1-36.9 months), and 50.6% were boys, 59.8% White individuals, 16.5% Black individuals, 23.7% other race, and 16.9% Hispanic/Latino individuals. Distinctive eye-gaze patterns were detected in toddlers with ASD, characterized by reduced gaze to social stimuli and to salient social moments during the movies, and previously unknown deficits in coordination of gaze with speech sounds. The area under the receiver operating characteristic curve discriminating ASD vs non-ASD using multiple gaze features was 0.90 (95% CI, 0.82-0.97). Conclusions and Relevance: The app reliably measured both known and new gaze biomarkers that distinguished toddlers with ASD vs typical development. These novel results may have potential for developing scalable autism screening tools, exportable to natural settings, and enabling data sets amenable to machine learning.

Educational classifications of autism spectrum disorder and intellectual disability among school-aged children in North Carolina: Associations with race, rurality, and resource availability.

Disparities exist in the recognition of autism spectrum disorder (ASD) and intellectual disability (ID) in racial/ethnic minorities in the United States. This study examined whether rurality, race/ethnicity, and low resource availability are associated with disparities in primary educational classifications of ASD and ID in North Carolina (NC). Descriptive maps were created. Multilevel logistic regression models examined two separate outcomes (mild ID vs. ASD; moderate/severe ID vs. ASD). For the interaction term included in the model (race/ethnicity and residence), predicted probabilities were estimated and plotted. The effects of other covariates were also estimated. Rural counties had fewer students with ASD and a greater number of students with ID compared to urban counties. The majority of students with ASD were non-Hispanic Whites, while the majority of students with ID were non-Hispanic Blacks. Compared to non-Hispanic White students, non-Hispanic Black students were overrepresented in the ID classification and underrepresented in the ASD classification across urban and rural areas. Indicators of low resource availability were also associated with higher probabilities of ID vs. ASD classification. Differences in primary educational classification based on urban-rural divide, race/ethnicity, and resource availability are important to understand as they may point to disparities that could have significant policy and service implications. Because disparities manifest through complex interactions between environmental, socioeconomic and system-level factors, reduction in these disparities will require broader approaches that address structural determinants. Future research should utilize disparity frameworks to understand differences in primary educational classifications of ASD and ID in the context of race/ethnicity and rurality. LAY SUMMARY: Rural counties in North Carolina had fewer students with ASD and a greater number of students with ID compared to urban counties. Compared to non-Hispanic White students, non-Hispanic Black students were over-represented in the ID educational classification and underrepresented in the ASD classification. Differences in classification of ASD and ID based on urban-rural divide, race/ethnicity, and resource availability may point to disparities that could have significant policy and service implications. Autism Res 2021, 14: 1046-1060. © 2021 International Society for Autism Research, Wiley Periodicals LLC.

A scalable computational approach to assessing response to name in toddlers with autism.

BACKGROUND: This study is part of a larger research program focused on developing objective, scalable tools for digital behavioral phenotyping. We evaluated whether a digital app delivered on a smartphone or tablet using computer vision analysis (CVA) can elicit and accurately measure one of the most common early autism symptoms, namely failure to respond to a name call. METHODS: During a pediatric primary care well-child visit, 910 toddlers, 17-37 months old, were administered an app on an iPhone or iPad consisting of brief movies during which the child's name was called three times by an examiner standing behind them. Thirty-seven toddlers were subsequently diagnosed with autism spectrum disorder (ASD). Name calls and children's behavior were recorded by the camera embedded in the device, and children's head turns were coded by both CVA and a human. RESULTS: CVA coding of response to name was found to be comparable to human coding. Based on CVA, children with ASD responded to their name significantly less frequently than children without ASD. CVA also revealed that children with ASD who did orient to their name exhibited a longer latency before turning their head. Combining information about both the frequency and the delay in response to name improved the ability to distinguish toddlers with and without ASD. CONCLUSIONS: A digital app delivered on an iPhone or iPad in real-world settings using computer vision analysis to quantify behavior can reliably detect a key early autism symptom-failure to respond to name. Moreover, the higher resolution offered by CVA identified a delay in head turn in toddlers with ASD who did respond to their name. Digital phenotyping is a promising methodology for early assessment of ASD symptoms.

Distance from Typical Scan Path When Viewing Complex Stimuli in Children with Autism Spectrum Disorder and its Association with Behavior.

Eye-tracking is often used to study attention in children with autism spectrum disorder (ASD). Previous research has identified multiple atypical patterns of attention in children with ASD based on areas-of-interest analysis. Fewer studies have investigated gaze path, a measure which is dependent on the dynamic content of the stimulus presented. Here, rather than looking at proportions of looking time to areas of interest, we calculated mean fixations frame-by-frame in a group of typically developing children (36 to 72 months) and determined the distance from those typical fixations for 155 children with ASD (27-95 months). Findings revealed that distance from the typical scan path among the children with ASD was associated with lower communication abilities and greater ASD symptomatology.

Gastrointestinal problems are associated with increased repetitive behaviors but not social communication difficulties in young children with autism spectrum disorders.

LAY ABSTRACT: Individuals with autism spectrum disorder are more likely than typically developing individuals to experience a range of gastrointestinal abnormalities, including chronic diarrhea, constipation, food sensitivities, and abdominal pain. These gastrointestinal symptoms have been associated with higher levels of irritability and aggressive behavior, but less is known about their relationship with core autism spectrum disorder symptoms. We investigated the relationship between autism spectrum disorder symptom severity and gastrointestinal symptoms while accounting for three associated behavioral symptom domains (Irritability, Aggressiveness, and Specific Fears), in a sample of 176 children (140 males and 36 females) ages 2-7 years old with autism spectrum disorder. A large majority (93.2%) of the sample had at least one reported gastrointestinal symptom, and most (88.1%) participants had more than one gastrointestinal symptom. Various types of gastrointestinal symptoms were reported; the most common symptoms reported were constipation, food limits, gas/bloating, and stomach pain. After accounting for each associated behavioral symptom domain, repetitive behaviors and stereotypies were significantly associated with gastrointestinal symptom severity. Increased severity of autism spectrum disorder symptoms was correlated with increased gastrointestinal symptom severity. Social and communication difficulties were not significantly associated with gastrointestinal symptom severity after accounting for associated behavioral symptoms. Our findings replicate a previously described association between irritability and aggression and gastrointestinal symptoms. Furthermore, we found that repetitive behaviors, but not social or communication symptoms, are associated with gastrointestinal symptom severity, even after accounting for associated behavioral symptoms. This suggests that gastrointestinal symptoms may exacerbate repetitive behaviors, or vice versa, independent from other associated behavioral symptoms.

Brief Report: Classifying Rates of Students with Autism and Intellectual Disability in North Carolina: Roles of Race and Economic Disadvantage.

We examined special education classifications among students aged 3-21 in North Carolina public schools, highlighting autism spectrum disorder (ASD) and intellectual disability (ID). Results revealed variability by county in ASD and ID prevalence, and in county-level ratios of ID vs. ASD classifications. Sociodemographic characteristics predicted proportion of ASD or ID within a county; correlations showed an association between race and ID, but not ASD. County's median household income predicted proportion of students classified as ASD and ID (opposite directions), controlling for number of students and gender. Variability was unlikely related to biological incidence, and more likely related to district/school practices, or differences in resources. Disparities warrant further examination to ensure that North Carolina's youth with disabilities access necessary, appropriate resources.

Infusion of human umbilical cord tissue mesenchymal stromal cells in children with autism spectrum disorder.

Ongoing neuroinflammation may contribute to symptoms of autism spectrum disorder (ASD) in at least a portion of affected individuals. Mesenchymal stromal cells (MSCs) have demonstrated the capacity to modulate neuroinflammation, but safety and feasibility of MSC administration in children with ASD have not been well established. In this open-label, phase I study, 12 children with ASD between 4 and 9 years of age were treated with intravenous (IV) infusions of human cord tissue mesenchymal stromal cells (hCT-MSCs), a third-party MSC product manufactured from unrelated donor umbilical cord tissue. Children received one, two, or three doses of 2 × 106 cells per kilogram at 2-month intervals. Clinical and laboratory evaluations were performed in person at baseline and 6 months and remotely at 12 months after the final infusion. Aside from agitation during the IV placement and infusion in some participants, hCT-MSCs were well tolerated. Five participants developed new class I anti-human leukocyte antigen (HLA) antibodies, associated with a specific lot of hCT-MSCs or with a partial HLA match between donor and recipient. These antibodies were clinically silent and not associated with any clinical manifestations to date. Six of 12 participants demonstrated improvement in at least two ASD-specific measures. Manufacturing and administration of hCT-MSCs appear to be safe and feasible in young children with ASD. Efficacy will be evaluated in a subsequent phase II randomized, placebo-controlled clinical trial.

A Phase II Randomized Clinical Trial of the Safety and Efficacy of Intravenous Umbilical Cord Blood Infusion for Treatment of Children with Autism Spectrum Disorder.

OBJECTIVE: To evaluate whether umbilical cord blood (CB) infusion is safe and associated with improved social and communication abilities in children with autism spectrum disorder (ASD). STUDY DESIGN: This prospective, randomized, placebo-controlled, double-blind study included 180 children with ASD, aged 2-7 years, who received a single intravenous autologous (n = 56) or allogeneic (n = 63) CB infusion vs placebo (n = 61) and were evaluated at 6 months postinfusion. RESULTS: CB infusion was safe and well tolerated. Analysis of the entire sample showed no evidence that CB was associated with improvements in the primary outcome, social communication (Vineland Adaptive Behavior Scales-3 [VABS-3] Socialization Domain), or the secondary outcomes, autism symptoms (Pervasive Developmental Disorder Behavior Inventory) and vocabulary (Expressive One-Word Picture Vocabulary Test). There was also no overall evidence of differential effects by type of CB infused. In a subanalysis of children without intellectual disability (ID), allogeneic, but not autologous, CB was associated with improvement in a larger percentage of children on the clinician-rated Clinical Global Impression-Improvement scale, but the OR for improvement was not significant. Children without ID treated with CB showed significant improvements in communication skills (VABS-3 Communication Domain), and exploratory measures including attention to toys and sustained attention (eye-tracking) and increased alpha and beta electroencephalographic power. CONCLUSIONS: Overall, a single infusion of CB was not associated with improved socialization skills or reduced autism symptoms. More research is warranted to determine whether CB infusion is an effective treatment for some children with ASD.