Development of webcam-collected and artificial-intelligence-derived social and cognitive performance measures for neurodevelopmental genetic syndromes.

This study focused on the development and initial psychometric evaluation of a set of online, webcam-collected, and artificial intelligence-derived patient performance measures for neurodevelopmental genetic syndromes (NDGS). Initial testing and qualitative input was used to develop four stimulus paradigms capturing social and cognitive processes, including social attention, receptive vocabulary, processing speed, and single-word reading. The paradigms were administered to a sample of 375 participants, including 163 with NDGS, 56 with idiopathic neurodevelopmental disability (NDD), and 156 neurotypical controls. Twelve measures were created from the four stimulus paradigms. Valid completion rates varied from 87 to 100% across measures, with lower but adequate completion rates in participants with intellectual disability. Adequate to excellent internal consistency reliability (α = 0.67 to 0.95) was observed across measures. Test-retest reproducibility at 1-month follow-up and stability at 4-month follow-up was fair to good (r = 0.40-0.73) for 8 of the 12 measures. All gaze-based measures showed evidence of convergent and discriminant validity with parent-report measures of other cognitive and behavioral constructs. Comparisons across NDGS groups revealed distinct patterns of social and cognitive functioning, including people with PTEN mutations showing a less impaired overall pattern and people with SYNGAP1 mutations showing more attentional, processing speed, and social processing difficulties relative to people with NFIX mutations. Webcam-collected performance measures appear to be a reliable and potentially useful method for objective characterization and monitoring of social and cognitive processes in NDGS and idiopathic NDD. Additional validation work, including more detailed convergent and discriminant validity analyses and examination of sensitivity to change, is needed to replicate and extend these observations.

Development of informant-report neurobehavioral survey scales for PTEN hamartoma tumor syndrome and related neurodevelopmental genetic syndromes.

There are few well-validated measures that are appropriate for assessing the full range of neurobehavioral presentations in PTEN hamartoma tumor syndrome (PHTS) and other neurodevelopmental genetic syndromes (NDGS). As potential therapeutics are developed, having reliable, valid, free, and easily accessible measures to track a range of neurobehavioral domains will be crucial for future clinical trials. This study focused on the development and initial psychometric evaluation of a set of freely available informant-report survey scales for PHTS-the Neurobehavioral Evaluation Tool (NET). Concept elicitation, quantitative ratings, and cognitive interviewing processes were conducted with stakeholders and clinician-scientist experts, used to identify the most important neurobehavioral domains for this population, and to ensure items were appropriate for the full range of individuals with PHTS. Results of this process identified a PHTS neurobehavioral impact model with 11 domains. The final NET scales assessing these domains were administered to a sample of 384 participants (median completion time = 20.6 min), including 32 people with PHTS, 141 with other NDGS, 47 with idiopathic neurodevelopmental disorder (NDD), and 164 neurotypical controls. Initial psychometric results for the total scores of each scale indicated very good model (ω = 0.83-0.99) and internal consistency reliability (α = 0.82-0.98) as well as excellent test-retest reproducibility at 1-month follow-up (r = 0.78-0.98) and stability at 4-month follow-up (r = 0.76-0.96). Conditional reliability estimates indicated very strong measurement precision in key score ranges for assessing PHTS and other people with NDGS and/or idiopathic NDD. Comparisons across domains between PHTS and the other groups revealed specific patterns of symptoms and functioning, including lower levels of challenging behavior and more developed daily living and executive functioning skills relative to other NDGS. The NET appears to be a reliable and potentially useful tool for clinical characterization and monitoring of neurobehavioral symptoms in PHTS and may also have utility in the assessment of other NDGS and idiopathic NDD. Additional validation work, including convergent and discriminant validity analyses, are needed to replicate and extend these observations.

Development and Validation of Objective and Quantitative Eye Tracking-Based Measures of Autism Risk and Symptom Levels.

OBJECTIVE: The primary aim of this study was to develop and validate eye tracking-based measures for estimating autism spectrum disorder (ASD) risk and quantifying autism symptom levels. METHOD: Eye tracking data were collected from youth during an initial evaluation visit, with administrators blinded to all clinical information. Consensus diagnoses were given by the multidisciplinary team. Participants viewed a 5-minute video that included 44 dynamic stimuli from 7 distinct paradigms while gaze was recorded. Gaze metrics were computed for temporally defined regions of interest. Autism risk and symptom indices aggregated gaze measures showing significant bivariate relationships with ASD diagnosis and Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) symptom severity levels in a training sample (75%, n = 150). Receiver operating characteristic curve analysis and nonparametric correlations were used to cross-validate findings in a test sample (25%; n = 51). RESULTS: Most children (n = 201, 92%) completed a valid eye tracking assessment (ages 1.6─17.6; 80% male; ASD n = 91, non-ASD n = 110). In the test subsample, the autism risk index had high accuracy for ASD diagnosis (area under the curve [AUC] = 0.86, 95% CI =0.75-0.95), whereas the autism symptom index was strongly associated with ADOS-2 total severity scores (r = 0.41, p < .001). Validity was not substantively attenuated after adjustment for language, nonverbal cognitive ability, or other psychopathology symptoms (r = 0.40-0.67, p > .001). CONCLUSION: Eye tracking measures appear to be useful quantitative, objective measures of ASD risk and autism symptom levels. If independently replicated and scaled for clinical use, eye tracking-based measures could be used to inform clinical judgment regarding ASD identification and to track autism symptom levels.

Development of an Objective Autism Risk Index Using Remote Eye Tracking.

OBJECTIVE: Abnormal eye gaze is a hallmark characteristic of autism spectrum disorder (ASD), and numerous studies have identified abnormal attention patterns in ASD. The primary aim of the present study was to create an objective, eye tracking-based autism risk index. METHOD: In initial and replication studies, children were recruited after referral for comprehensive multidisciplinary evaluation of ASD and subsequently grouped by clinical consensus diagnosis (ASD n = 25/15, non-ASD n = 20/19 for initial/replication samples). Remote eye tracking was blinded to diagnosis and included multiple stimuli. Dwell times were recorded to each a priori-defined region of interest (ROI) and averaged across ROIs to create an autism risk index. Receiver operating characteristic curve analyses examined classification accuracy. Correlations with clinical measures evaluated whether the autism risk index was associated with autism symptom severity independent of language ability. RESULTS: In both samples, the autism risk index had high diagnostic accuracy (area under the curve [AUC] = 0.91 and 0.85, 95% CIs = 0.81-0.98 and 0.71-0.96), was strongly associated with Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) severity scores (r = 0.58 and 0.59, p < .001), and not significantly correlated with language ability (r ≤| -0.28|, p > .095). CONCLUSION: The autism risk index may be a useful quantitative and objective measure of risk for autism in at-risk settings. Future research in larger samples is needed to cross-validate these findings. If validated and scaled for clinical use, this measure could inform clinical judgment regarding ASD diagnosis and track symptom improvements.

Development and psychometric evaluation of a psychosocial quality-of-life questionnaire for individuals with autism and related developmental disorders.

This study investigated the psychometric properties of the Child and Family Quality of Life scale, a measure of psychosocial quality of life in those with autism and related developmental disorders. Parents of 212 children suspected of autism spectrum disorder completed the Child and Family Quality of Life prior to a diagnostic evaluation. Results indicated that the Child and Family Quality of Life measured six unique quality-of-life constructs (child, family/caregiver, financial, external support, partner relationship, and coping), had good reliability across score ranges and exhibited expected patterns of convergent validity. Caregivers of autism spectrum disorder-affected children reported reduced family quality of life prior to the time of diagnosis relative to caregivers of children with other developmental disabilities. The Child and Family Quality of Life is a brief, reliable measure for assessing psychosocial quality of life in families affected by developmental disability. This study is the first to demonstrate impairments in family quality of life early in the developmental course of autism spectrum disorder, prior to formal diagnosis. In addition to traditional child-focused intervention strategies, families with autism spectrum disorder-affected children require early, broad intervention strategies that positively impact the whole family.

Identifying autism in a brief observation.

BACKGROUND: Pediatricians, neurologists, and geneticists are important sources for autism surveillance, screening, and referrals, but practical time constraints limit the clinical utility of behavioral observations. We analyzed behaviors under favorable conditions (ie, video of autism evaluations reviewed by experts) to determine what is optimally observable within 10-minute samples, asked for referral impressions, and compared these to formal screening and developmental testing results. METHODS: Participants (n = 42, aged 15 to 33 months) were typically developing controls and children who screened positive during universal autism screening within a large community pediatric practice. Diagnostic evaluations were performed after screening to determine group status (autism, language delay, or typical). Licensed psychologists with toddler and autism expertise, unaware of diagnostic status, analyzed two 10-minute video samples of participants' autism evaluations, measuring 5 behaviors: Responding, Initiating, Vocalizing, Play, and Response to Name. Raters were asked for autism referral impressions based solely on individual 10-minute observations. RESULTS: Children who had autism showed more typical behavior (89% of the time) than atypical behavior (11%) overall. Expert raters missed 39% of cases in the autism group as needing autism referrals based on brief but highly focused observations. Significant differences in cognitive and adaptive development existed among groups, with receptive language skills differentiating the 3 groups. CONCLUSIONS: Brief clinical observations may not provide enough information about atypical behaviors to reliably detect autism risk. High prevalence of typical behaviors in brief samples may distort clinical impressions of atypical behaviors. Formal screening tools and general developmental testing provide critical data for accurate referrals.

Validation of proposed DSM-5 criteria for autism spectrum disorder.

OBJECTIVE: The primary aim of the present study was to evaluate the validity of proposed DSM-5 criteria for autism spectrum disorder (ASD). METHOD: We analyzed symptoms from 14,744 siblings (8,911 ASD and 5,863 non-ASD) included in a national registry, the Interactive Autism Network. Youth 2 through 18 years of age were included if at least one child in the family was diagnosed with ASD. Caregivers reported symptoms using the Social Responsiveness Scale and the Social Communication Questionnaire. The structure of autism symptoms was examined using latent variable models that included categories, dimensions, or hybrid models specifying categories and subdimensions. Diagnostic efficiency statistics evaluated the proposed DSM-5 algorithm in identifying ASD. RESULTS: A hybrid model that included both a category (ASD versus non-ASD) and two symptom dimensions (social communication/interaction and restricted/repetitive behaviors) was more parsimonious than all other models and replicated across measures and subsamples. Empirical classifications from this hybrid model closely mirrored clinical ASD diagnoses (90% overlap), implying a broad ASD category distinct from non-ASD. DSM-5 criteria had superior specificity relative to DSM-IV-TR criteria (0.97 versus 0.86); however sensitivity was lower (0.81 versus 0.95). Relaxing DSM-5 criteria by requiring one less symptom criterion increased sensitivity (0.93 versus 0.81), with minimal reduction in specificity (0.95 versus 0.97). CONCLUSIONS: Results supported the validity of proposed DSM-5 criteria for ASD as provided in Phase I Field Trials criteria. Increased specificity of DSM-5 relative to DSM-IV-TR may reduce false positive diagnoses, a particularly relevant consideration for low base rate clinical settings. Phase II testing of DSM-5 should consider a relaxed algorithm, without which as many as 12% of ASD-affected individuals, particularly females, will be missed. Relaxed DSM-5 criteria may improve identification of ASD, decreasing societal costs through appropriate early diagnosis and maximizing intervention resources.

Face processing in children with autism: effects of stimulus contents and type.

Recent eye tracking studies of face processing have produced differing accounts of how and whether children with autism differ from their typically developing peers. The two groups' gaze patterns appear to differ for dynamic videos of social scenes, but not for static photos of isolated individuals. The present study replicated and extended previous research by comparing the gaze patterns of individuals with and without autism for four types of stimuli: social dynamic, social static, isolated dynamic, and isolated static. Participants with autism differed from their typically developing peers only for social-dynamic stimuli; fixation durations were decreased for eye regions and increased for body regions. Further, these fixation durations predicted scores on a measure of social responsiveness. These findings reconcile differences in previous reports by identifying the specific social and dynamic task components associated with autism-related face processing impairments.