Cognitive Disengagement Syndrome in Young Autistic Children, Children with ADHD, and Autistic Children with ADHD.

OBJECTIVE: Cognitive Disengagement Syndrome (CDS; previously called Sluggish Cognitive Tempo) refers to a constellation of cognitive and motor behaviors characterized by a predisposition toward mind wandering (cognitive subdomain) and slowed motor behavior (hypoactive). While there are a number of studies linking CDS traits to greater global impairment in children with attention-deficit/hyperactivity disorder (ADHD) and autistic children, there are few studies examining the prevalence and impact of CDS traits in autistic children with co-occurring ADHD (Autistic+ADHD). The current study explored CDS traits in autistic children with and without co-occurring ADHD, children with ADHD, and neurotypical children. METHODS: Participants were 196 children between 3- and 7-years-of-age comprising four groups: Neurotypical (N = 44), ADHD (N = 51), Autistic (N = 55), and Autistic+ADHD (N = 46). CDS traits, social and communication skills, repetitive behaviors, and sensory processing were all assessed via parent report. RESULTS: Children diagnosed with ADHD, autistic children, and Autistic+ADHD children exhibited similar levels of overall CDS traits. However, when explored separately, Autistic+ADHD children had higher cognitive CDS trait scores compared to children with ADHD alone. Both overall CDS traits and the cognitive subdomain were associated with greater social difficulties, particularly social withdrawal, higher levels of repetitive behaviors, and more sensory sensitivities, regardless of diagnosis. CONCLUSIONS: Findings suggest that CDS traits may be an additional factor directly impact functional outcomes in both autistic and ADHD children. As such, clinicians should be assessing CDS traits in addition to other clinical domains associated with ADHD and autism when developing intervention plans for young neurodiverse children.

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.

Individual differences in reading aloud: a mega-study, item effects, and some models.

Normal individual differences are rarely considered in the modelling of visual word recognition--with item response time effects and neuropsychological disorders being given more emphasis--but such individual differences can inform and test accounts of the processes of reading. We thus had 100 participants read aloud words selected to assess theoretically important item response time effects on an individual basis. Using two major models of reading aloud--DRC and CDP+--we estimated numerical parameters to best model each individual's response times to see if this would allow the models to capture the effects, individual differences in them and the correlations among these individual differences. It did not. We therefore created an alternative model, the DRC-FC, which successfully captured more of the correlations among individual differences, by modifying the locus of the frequency effect. Overall, our analyses indicate that (i) even after accounting for individual differences in general speed, several other individual difference in reading remain significant; and (ii) these individual differences provide critical tests of models of reading aloud. The database thus offers a set of important constraints for future modelling of visual word recognition, and is a step towards integrating such models with other knowledge about individual differences in reading.

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.

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.

Computer Vision Analysis of Caregiver-Child Interactions in Children with Neurodevelopmental Disorders: A Preliminary Report.

We report preliminary results of computer vision analysis of caregiver-child interactions during free play with children diagnosed with autism (N = 29, 41-91 months), attention-deficit/hyperactivity disorder (ADHD, N = 22, 48-100 months), or combined autism + ADHD (N = 20, 56-98 months), and neurotypical children (NT, N = 7, 55-95 months). We conducted micro-analytic analysis of 'reaching to a toy,' as a proxy for initiating or responding to a toy play bout. Dyadic analysis revealed two clusters of interaction patterns, which differed in frequency of 'reaching to a toy' and caregivers' contingent responding to the child's reach for a toy by also reaching for a toy. Children in dyads with higher caregiver responsiveness had less developed language, communication, and socialization skills. Clusters were not associated with diagnostic groups. These results hold promise for automated methods of characterizing caregiver responsiveness in dyadic interactions for assessment and outcome monitoring in clinical trials.

The Autism Biomarkers Consortium for Clinical Trials: Initial Evaluation of a Battery of Candidate EEG Biomarkers.

OBJECTIVE: Numerous candidate EEG biomarkers have been put forward for use in clinical research on autism spectrum disorder (ASD), but biomarker development has been hindered by limited attention to the psychometric properties of derived variables, inconsistent results across small studies, and variable methodology. The authors evaluated the basic psychometric properties of a battery of EEG assays for their potential suitability as biomarkers in clinical trials. METHODS: This was a large, multisite, naturalistic study in 6- to 11-year-old children who either had an ASD diagnosis (N=280) or were typically developing (N=119). The authors evaluated an EEG battery composed of well-studied assays of resting-state activity, face perception (faces task), biological motion perception, and visual evoked potentials (VEPs). Biomarker psychometrics were evaluated in terms of acquisition rates, construct performance, and 6-week stability. Preliminary evaluation of use was explored through group discrimination and phenotypic correlations. RESULTS: Three assays (resting state, faces task, and VEP) show promise in terms of acquisition rates and construct performance. Six-week stability values in the ASD group were moderate (intraclass correlations ≥0.66) for the faces task latency of the P1 and N170, the VEP amplitude of N1 and P1, and resting alpha power. Group discrimination and phenotype correlations were primarily observed for the faces task P1 and N170. CONCLUSIONS: In the context of a large-scale, rigorous evaluation of candidate EEG biomarkers for use in ASD clinical trials, neural response to faces emerged as a promising biomarker for continued evaluation. Resting-state activity and VEP yielded mixed results. The study's biological motion perception assay failed to display construct performance. The results provide information about EEG biomarker performance that is relevant for the next stage of biomarker development efforts focused on context of use.

Evaluation of clinical assessments of social abilities for use in autism clinical trials by the autism biomarkers consortium for clinical trials.

Clinical trials in autism spectrum disorder (ASD) often rely on clinician rating scales and parent surveys to measure autism-related features and social behaviors. To aid in the selection of these assessments for future clinical trials, the Autism Biomarkers Consortium for Clinical Trials (ABC-CT) directly compared eight common instruments with respect to acquisition rates, sensitivity to group differences, equivalence across demographic sub-groups, convergent validity, and stability over a 6-week period. The sample included 280 children diagnosed with ASD (65 girls) and 119 neurotypical children (36 girls) aged from 6 to 11 years. Full scale IQ for ASD ranged from 60 to 150 and for neurotypical ranged from 86 to 150. Instruments measured clinician global assessment and autism-related behaviors, social communication abilities, adaptive function, and social withdrawal behavior. For each instrument, we examined only the scales that measured social or communication functioning. Data acquisition rates were at least 97.5% at T1 and 95.7% at T2. All scales distinguished diagnostic groups. Some scales significantly differed by participant and/or family demographic characteristics. Within the ASD group, most clinical instruments exhibited weak (≥ |0.1|) to moderate (≥ |0.4|) intercorrelations. Short-term stability was moderate (ICC: 0.5-0.75) to excellent (ICC: >0.9) within the ASD group. Variations in the degree of stability may inform viability for different contexts of use, such as identifying clinical subgroups for trials versus serving as a modifiable clinical outcome. All instruments were evaluated in terms of their advantages and potential concerns for use in clinical trials.

The Selective Social Attention task in children with autism spectrum disorder: Results from the Autism Biomarkers Consortium for Clinical Trials (ABC-CT) feasibility study.

The Selective Social Attention (SSA) task is a brief eye-tracking task involving experimental conditions varying along socio-communicative axes. Traditionally the SSA has been used to probe socially-specific attentional patterns in infants and toddlers who develop autism spectrum disorder (ASD). This current work extends these findings to preschool and school-age children. Children 4- to 12-years-old with ASD (N = 23) and a typically-developing comparison group (TD; N = 25) completed the SSA task as well as standardized clinical assessments. Linear mixed models examined group and condition effects on two outcome variables: percent of time spent looking at the scene relative to scene presentation time (%Valid), and percent of time looking at the face relative to time spent looking at the scene (%Face). Age and IQ were included as covariates. Outcome variables' relationships to clinical data were assessed via correlation analysis. The ASD group, compared to the TD group, looked less at the scene and focused less on the actress' face during the most socially-engaging experimental conditions. Additionally, within the ASD group, %Face negatively correlated with SRS total T-scores with a particularly strong negative correlation with the Autistic Mannerism subscale T-score. These results highlight the extensibility of the SSA to older children with ASD, including replication of between-group differences previously seen in infants and toddlers, as well as its ability to capture meaningful clinical variation within the autism spectrum across a wide developmental span inclusive of preschool and school-aged children. The properties suggest that the SSA may have broad potential as a biomarker for ASD.

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.

Patterns of Intervention Utilization Among School-Aged Children with Autism Spectrum Disorder: Findings from a Multi-Site Research Consortium.

When designing and interpreting results from clinical trials evaluating treatments for children on the autism spectrum, a complicating factor is that most children receive a range of concurrent treatments. Thus, it is important to better understand the types and hours of interventions that participants typically receive as part of standard of care, as well as to understand the child, family, and geographic factors that are associated with different patterns of service utilization. In this multi-site study, we interviewed 280 caregivers of 6-to-11-year-old school-aged children on the autism spectrum about the types and amounts of interventions their children received in the prior 6 weeks. Reported interventions were coded as "evidence-based practice" or "other interventions," reflecting the level of empirical support. Results indicated that children received a variety of interventions with varying levels of empirical evidence and a wide range of hours (0 to 79.3 hours/week). Children with higher autism symptom levels, living in particular states, and who identified as non-Hispanic received more evidence-based intervention hours. Higher parental education level related to more hours of other interventions. Children who were younger, had lower cognitive ability, and with higher autism symptom levels received a greater variety of interventions overall. Thus, based on our findings, it would seem prudent when designing clinical trials to take into consideration a variety of factors including autism symptom levels, age, cognitive ability, ethnicity, parent education and geographic location. Future research should continue to investigate the ethnic, racial, and socioeconomic influences on school-aged intervention services.

Identifying Age Based Maturation in the ERP Response to Faces in Children With Autism: Implications for Developing Biomarkers for Use in Clinical Trials.

Recent proposals have suggested the potential for neural biomarkers to improve clinical trial processes in neurodevelopmental conditions; however, few efforts have identified whether chronological age-based adjustments will be necessary (as used in standardized behavioral assessments). Event-related potentials (ERPs) demonstrate early differences in the processing of faces vs. objects in the visual processing system by 4 years of age and age-based improvement (decreases in latency) through adolescence. Additionally, face processing has been proposed to be related to social skills as well as autistic social-communication traits. While previous reports suggest delayed latency in individuals with autism spectrum disorder (ASD), extensive individual and age based heterogeneity exists. In this report, we utilize a sample of 252 children with ASD and 118 children with typical development (TD), to assess the N170 and P100 ERP component latencies (N170L and P100L, respectively), to upright faces, the face specificity effect (difference between face and object processing), and the inversion effect (difference between face upright and inverted processing) in relation to age. First, linear mixed models (LMMs) were fitted with fixed effect of age at testing and random effect of participant, using all available data points to characterize general age-based development in the TD and ASD groups. Second, LMM models using only the TD group were used to calculate age-based residuals in both groups. The purpose of residualization was to assess how much variation in ASD participants could be accounted for by chronological age-related changes. Our data demonstrate that the N170L and P100L responses to upright faces appeared to follow a roughly linear relationship with age. In the ASD group, the distribution of the age-adjusted residual values suggest that ASD participants were more likely to demonstrate slower latencies than would be expected for a TD child of the same age, similar to what has been identified using unadjusted values. Lastly, using age-adjusted values for stratification, we found that children who demonstrated slowed age-adjusted N170L had lower verbal and non-verbal IQ and worse face memory. These data suggest that age must be considered in assessing the N170L and P100L response to upright faces as well, and these adjusted values may be used to stratify children within the autism spectrum.

Adaptive Behavior in Young Autistic Children: Associations with Irritability and ADHD Symptoms.

Attention-deficit/hyperactivity disorder (ADHD) symptoms affect 40-60% of autistic children and have been linked to differences in adaptive behavior. It is unclear whether adaptive behavior in autistic youth is directly impacted by co-occurring ADHD symptoms or by another associated feature of both autism and ADHD, such as increased irritability. The current study examined relationships between irritability, ADHD symptoms, and adaptive behavior in 3- to 7-year-old autistic children. Results suggest that, after adjusting for co-occurring ADHD symptoms, higher levels of irritability are associated with differences in social adaptive behavior specifically. Understanding relationships between irritability, ADHD, and adaptive behavior in autistic children is critical because measures of adaptive behavior, such as the Vineland Scales of Adaptive Functioning, are often used as a proxy for global functioning, as well as for developing intervention plans and measuring outcomes as primary endpoints in clinical trials.

The autism biomarkers consortium for clinical trials: evaluation of a battery of candidate eye-tracking biomarkers for use in autism clinical trials.

BACKGROUND: Eye tracking (ET) is a powerful methodology for studying attentional processes through quantification of eye movements. The precision, usability, and cost-effectiveness of ET render it a promising platform for developing biomarkers for use in clinical trials for autism spectrum disorder (ASD). METHODS: The autism biomarkers consortium for clinical trials conducted a multisite, observational study of 6-11-year-old children with ASD (n = 280) and typical development (TD, n = 119). The ET battery included: Activity Monitoring, Social Interactive, Static Social Scenes, Biological Motion Preference, and Pupillary Light Reflex tasks. A priori, gaze to faces in Activity Monitoring, Social Interactive, and Static Social Scenes tasks were aggregated into an Oculomotor Index of Gaze to Human Faces (OMI) as the primary outcome measure. This work reports on fundamental biomarker properties (data acquisition rates, construct validity, six-week stability, group discrimination, and clinical relationships) derived from these assays that serve as a base for subsequent development of clinical trial biomarker applications. RESULTS: All tasks exhibited excellent acquisition rates, met expectations for construct validity, had moderate or high six-week stabilities, and highlighted subsets of the ASD group with distinct biomarker performance. Within ASD, higher OMI was associated with increased memory for faces, decreased autism symptom severity, and higher verbal IQ and pragmatic communication skills. LIMITATIONS: No specific interventions were administered in this study, limiting information about how ET biomarkers track or predict outcomes in response to treatment. This study did not consider co-occurrence of psychiatric conditions nor specificity in comparison with non-ASD special populations, therefore limiting our understanding of the applicability of outcomes to specific clinical contexts-of-use. Research-grade protocols and equipment were used; further studies are needed to explore deployment in less standardized contexts. CONCLUSIONS: All ET tasks met expectations regarding biomarker properties, with strongest performance for tasks associated with attention to human faces and weakest performance associated with biological motion preference. Based on these data, the OMI has been accepted to the FDA's Biomarker Qualification program, providing a path for advancing efforts to develop biomarkers for use in clinical trials.

The development of memory maintenance: children's use of phonological rehearsal and attentional refreshment in working memory tasks.

Past research suggests that children begin to phonologically rehearse at around 7 years of age. Less is known regarding the development of refreshment, an attention-based maintenance mechanism. Therefore, the use of these two maintenance methods by 6- and 8-year-olds was assessed using memory span tasks that varied in their opportunities for maintenance activity. Experiment 1 showed that nonverbal processing impaired both groups' performance to similar extents. Experiment 2 employed phonologically similar or dissimilar memory items and compared the effects of verbal versus nonverbal processing on recall. Both groups showed evidence of phonological maintenance under nonverbal processing but not under verbal processing. Furthermore, nonverbal processing again impaired recall. Verbal processing was also more detrimental to performance in 8-year-olds than in 6-year-olds. Together, the results suggest that nonverbal processing impairs recall by obstructing refreshment and that developmental change in maintenance between 6 and 8 years of age consists primarily of an increase in phonological rehearsal.

A Six-Minute Measure of Vocalizations in Toddlers with Autism Spectrum Disorder.

To improve early identification of autism spectrum disorder (ASD), we need objective, reliable, and accessible measures. To that end, a previous study demonstrated that a tablet-based application (app) that assessed several autism risk behaviors distinguished between toddlers with ASD and non-ASD toddlers. Using vocal data collected during this study, we investigated whether vocalizations uttered during administration of this app can distinguish among toddlers aged 16-31 months with typical development (TD), language or developmental delay (DLD), and ASD. Participant's visual and vocal responses were recorded using the camera and microphone in a tablet while toddlers watched movies designed to elicit behaviors associated with risk for ASD. Vocalizations were then coded offline. Results showed that (a) children with ASD and DLD were less likely to produce words during app administration than TD participants; (b) the ratio of syllabic vocalizations to all vocalizations was higher among TD than ASD or DLD participants; and (c) the rates of nonsyllabic vocalizations were higher in the ASD group than in either the TD or DLD groups. Those producing more nonsyllabic vocalizations were 24 times more likely to be diagnosed with ASD. These results lend support to previous findings that early vocalizations might be useful in identifying risk for ASD in toddlers and demonstrate the feasibility of using a scalable tablet-based app for assessing vocalizations in the context of a routine pediatric visit. LAY SUMMARY: Although parents often report symptoms of autism spectrum disorder (ASD) in infancy, we are not yet reliably diagnosing ASD until much later in development. A previous study tested a tablet-based application (app) that recorded behaviors we know are associated with ASD to help identify children at risk for the disorder. Here we measured how children vocalize while they watched the movies presented on the tablet. Children with ASD were less likely to produce words, less likely to produce speechlike sounds, and more likely to produce atypical sounds while watching these movies. These measures, combined with other behaviors measured by the app, might help identify which children should be evaluated for ASD. Autism Res 2020, 13: 1373-1382. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

The Autism Biomarkers Consortium for Clinical Trials (ABC-CT): Scientific Context, Study Design, and Progress Toward Biomarker Qualification.

Clinical research in neurodevelopmental disorders remains reliant upon clinician and caregiver measures. Limitations of these approaches indicate a need for objective, quantitative, and reliable biomarkers to advance clinical research. Extant research suggests the potential utility of multiple candidate biomarkers; however, effective application of these markers in trials requires additional understanding of replicability, individual differences, and intra-individual stability over time. The Autism Biomarkers Consortium for Clinical Trials (ABC-CT) is a multi-site study designed to investigate a battery of electrophysiological (EEG) and eye-tracking (ET) indices as candidate biomarkers for autism spectrum disorder (ASD). The study complements published biomarker research through: inclusion of large, deeply phenotyped cohorts of children with ASD and typical development; a longitudinal design; a focus on well-evidenced candidate biomarkers harmonized with an independent sample; high levels of clinical, regulatory, technical, and statistical rigor; adoption of a governance structure incorporating diverse expertise in the ASD biomarker discovery and qualification process; prioritization of open science, including creation of a repository containing biomarker, clinical, and genetic data; and use of economical and scalable technologies that are applicable in developmental populations and those with special needs. The ABC-CT approach has yielded encouraging results, with one measure accepted into the FDA's Biomarker Qualification Program to date. Through these advances, the ABC-CT and other biomarker studies in progress hold promise to deliver novel tools to improve clinical trials research in ASD.

Biomarker Acquisition and Quality Control for Multi-Site Studies: The Autism Biomarkers Consortium for Clinical Trials.

The objective of the Autism Biomarkers Consortium for Clinical Trials (ABC-CT) is to evaluate a set of lab-based behavioral video tracking (VT), electroencephalography (EEG), and eye tracking (ET) measures for use in clinical trials with children with autism spectrum disorder (ASD). Within the larger organizational structure of the ABC-CT, the Data Acquisition and Analytic Core (DAAC) oversees the standardization of VT, EEG, and ET data acquisition, data processing, and data analysis. This includes designing and documenting data acquisition and analytic protocols and manuals; facilitating site training in acquisition; data acquisition quality control (QC); derivation and validation of dependent variables (DVs); and analytic deliverables including preparation of data for submission to the National Database for Autism Research (NDAR). To oversee consistent application of scientific standards and methodological rigor for data acquisition, processing, and analytics, we developed standard operating procedures that reflect the logistical needs of multi-site research, and the need for well-articulated, transparent processes that can be implemented in future clinical trials. This report details the methodology of the ABC-CT related to acquisition and QC in our Feasibility and Main Study phases. Based on our acquisition metrics from a preplanned interim analysis, we report high levels of acquisition success utilizing VT, EEG, and ET experiments in a relatively large sample of children with ASD and typical development (TD), with data acquired across multiple sites and use of a manualized training and acquisition protocol.

Methodological considerations in the use of Noldus EthoVision XT video tracking of children with autism in multi-site studies.

Animal models of autism spectrum disorders (ASD) contribute to understanding of the role of genetics and the biological mechanisms underlying behavioral phenotypes and inform the development of potential treatments. Translational biomarkers are needed that can both validate these models and facilitate behavioral testing paradigms for ASD in humans. Automated video tracking of movement patterns and positions recorded from overhead cameras is routinely applied in behavioral paradigms designed to elicit core behavioral manifestations of ASD in rodent models. In humans, laboratory-based observations are a common semi-naturalistic context for assessing a variety of behaviors relevant to ASD such as social engagement, play, and attention. We present information learned and suggest guidelines for designing, recording, acquiring, and evaluating video tracking data of human movement patterns based on our experience in a multi-site video tracking study of children with ASD in the context of a parent-child, laboratory-based play interaction.