Altered engagement of the speech motor network is associated with reduced phonological working memory in autism.

Nonword repetition, a common clinical measure of phonological working memory, involves component processes of speech perception, working memory, and speech production. Autistic children often show behavioral challenges in nonword repetition, as do many individuals with communication disorders. It is unknown which subprocesses of phonological working memory are vulnerable in autistic individuals, and whether the same brain processes underlie the transdiagnostic difficulty with nonword repetition. We used functional magnetic resonance imaging (fMRI) to investigate the brain bases for nonword repetition challenges in autism. We compared activation during nonword repetition in functional brain networks subserving speech perception, working memory, and speech production between neurotypical and autistic children. Autistic children performed worse than neurotypical children on nonword repetition and had reduced activation in response to increasing phonological working memory load in the supplementary motor area. Multivoxel pattern analysis within the speech production network classified shorter vs longer nonword-repetition trials less accurately for autistic than neurotypical children. These speech production motor-specific differences were not observed in a group of children with reading disability who had similarly reduced nonword repetition behavior. These findings suggest that atypical function in speech production brain regions may contribute to nonword repetition difficulties in autism.

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.

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.

The central role of disgust in disorders of food avoidance.

BACKGROUND: Individuals with extreme food avoidance such as Avoidant Restrictive Food Intake Disorder (ARFID) experience impairing physical and mental health consequences from nutrition of insufficient variety or/and quantity. Identifying mechanisms contributing to food avoidance is essential to develop effective interventions. Anxiety figures prominently in theoretical models of food avoidance; however, there is limited evidence that repeated exposures to foods increases approach behavior in ARFID. Studying disgust, and relationships between disgust and anxiety, may offer novel insights, as disgust is functionally associated with avoidance of contamination from pathogens (as may occur via ingestion) and is largely resistant to extinction. METHOD: This exploratory, cross-sectional study included data from 1,644 adults who completed an online questionnaire. Participant responses were used to measure ARFID classification, picky eating, sensory sensitivity, disgust, and anxiety. Structural equation modeling tested a measurement model of latent disgust and anxiety factors as measured by self-reported frequency of disgust and anxiety reactions. Mediational models were used to explore causal ordering. RESULTS: A latent disgust factor was more strongly related to severity of picky eating (B ≈ 0.4) and ARFID classification (B ≈ 0.6) than the latent anxiety factor (B ≈ 0.1). Disgust partially mediated the association between anxiety and picky eating and fully mediated the association between anxiety and ARFID. Models testing the reverse causal ordering demonstrated poorer fit. Findings suggest anxiety may be associated with food avoidance in part due to increased disgust. CONCLUSIONS: Disgust may play a prominent role in food avoidance. Findings may inform novel approaches to treatment.

Feeling and body investigators (FBI): ARFID division-An acceptance-based interoceptive exposure treatment for children with ARFID.

OBJECTIVE: Individuals with Avoidant Restrictive Food Intake Disorder (ARFID) experience impairing health consequences from insufficient nutritional variety and/or quantity. Early medical conditions and/or somatic symptoms such as abdominal pain may lead some with ARFID to experience somatic sensations as aversive. As such, food avoidance may be part of a broader behavioral repertoire aimed at suppressing bodily sensations. Avoiding these necessary and informative signals (e.g., growls of hunger) may subvert the emergence of healthy self-awareness and self-regulation. Teaching children with ARFID to engage adaptively with bodily sensations may help decrease aversiveness, increase self-awareness, and increase approach behaviors. METHOD: Drawing from interventions for panic disorder and irritable bowel syndrome, we developed an acceptance-based interoceptive exposure treatment for young children with ARFID, Feeling and Body Investigators (FBI)-ARFID Division. Using playful cartoons and developmentally sensitive exposures, we teach young children how to map interoceptive sensations onto meanings (e.g., emotions) and actions (e.g., if I feel nervous, I'll hold someone's hand). RESULTS: We present a case study of a 4-year old child with lifelong poor appetite/food indifference. DISCUSSION: Some individuals with ARFID may avoid food to avoid internal sensations. Developmentally appropriate interoceptive exposures may decrease ARFID symptoms while increasing more general self-regulation skills.

Validation of eye-tracking measures of social attention as a potential biomarker for autism clinical trials.

Social communication impairments are a core feature of autism spectrum disorder (ASD), and this class of symptoms is a target for treatments for the disorder. Measures of social attention, assessed via eye-gaze tracking (EGT), have been proposed as an early efficacy biomarker for clinical trials targeting social communication skills. EGT measures have been shown to differentiate children with ASD from typical children; however, there is less known about their relationships with social communication outcome measures that are typically used in ASD clinical trials. In the present study, an EGT task involving viewing a videotape of an actor making bids for a child's attention was evaluated in 25 children with ASD aged 24-72 months. Children's attention to the actor during the dyadic bid condition measured via EGT was found to be strongly associated with five well-validated caregiver-reported outcome measures that are commonly used to assess social communication in clinical trials. These results highlight the convergent validity of EGT measures of social attention in relation to caregiver-reported clinical measures. EGT holds promise as a non-invasive, quantitative, and objective biomarker that is associated with social communication abilities in children with ASD. Autism Res 2018, 11: 166-174. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Eye-gaze tracking (EGT), an automated tool that tracks eye-gaze patterns, might help measure outcomes in clinical trials investigating interventions to treat autism spectrum disorders. In this study, an EGT task was evaluated in children with ASD, who watched a video with an actor talking directly to them. Patterns of eye-gaze were associated with caregiver-reported measures of social communication that are used in clinical trials. We show EGT may be a promising objective tool measuring outcomes.

Autism Behavior Inventory: A Novel Tool for Assessing Core and Associated Symptoms of Autism Spectrum Disorder.

OBJECTIVE: Autism Behavior Inventory (ABI) is a new measure for assessing changes in core and associated symptoms of autism spectrum disorder (ASD) in participants (ages: 3 years-adulthood) diagnosed with ASD. It is a web-based tool with five domains (two ASD core domains: social communication, restrictive and repetitive behaviors; three associated domains: mental health, self-regulation, and challenging behavior). This study describes design, development, and initial psychometric properties of the ABI. METHODS: ABI items were generated following review of existing measures and inputs from expert clinicians. Initial ABI scale contained 161 items that were reduced to fit a factor analytic model, retaining items of adequate reliability. Two versions of the scale, ABI-full (ABI-F; 93 items) and ABI-short version (ABI-S; 36 items), were developed and evaluated for psychometric properties, including validity comparisons with commonly used measures. Both scales were administered to parents and healthcare professionals (HCPs) involved with study participants. RESULTS: Test-retest reliability (intraclass correlation coefficient [ICC] = 0.79) for parent ratings on ABI was robust and compared favorably to existing scales. Test-retest correlations for HCP ratings were generally lower versus parent ratings. ABI core domains and comparison measures strongly correlated (r ≥ 0.70), demonstrating good concurrent validity. CONCLUSIONS: Overall, ABI demonstrates promise as a tool for measuring change in core symptoms of autism in ASD clinical studies, with further validation required.

Shared neuroanatomical substrates of impaired phonological working memory across reading disability and autism.

BACKGROUND: Individuals with reading disability or individuals with autism spectrum disorder (ASD) are characterized, respectively, by their difficulties in reading or social communication, but both groups often have impaired phonological working memory (PWM). It is not known whether the impaired PWM reflects distinct or shared neuroanatomical abnormalities in these two diagnostic groups. METHODS: White-matter structural connectivity via diffusion weighted imaging was examined in sixty-four children, ages 5-17 years, with reading disability, ASD, or typical development (TD), who were matched in age, gender, intelligence, and diffusion data quality. RESULTS: Children with reading disability and children with ASD exhibited reduced PWM compared to children with TD. The two diagnostic groups showed altered white-matter microstructure in the temporo-parietal portion of the left arcuate fasciculus (AF) and in the temporo-occipital portion of the right inferior longitudinal fasciculus (ILF), as indexed by reduced fractional anisotropy and increased radial diffusivity. Moreover, the structural integrity of the right ILF was positively correlated with PWM ability in the two diagnostic groups, but not in the TD group. CONCLUSIONS: These findings suggest that impaired PWM is transdiagnostically associated with shared neuroanatomical abnormalities in ASD and reading disability. Microstructural characteristics in left AF and right ILF may play important roles in the development of PWM. The right ILF may support a compensatory mechanism for children with impaired PWM.

Direct magnitude estimation of articulation rate in boys with fragile X syndrome.

PURPOSE: To compare the perceived articulation rate of boys with fragile X syndrome (FXS) with that of chronologically age-matched (CA) boys and to determine segmental and/or prosodic factors that account for perceived rate. METHOD: Ten listeners used direct magnitude estimation procedures to judge the articulation rates of 7 boys with FXS only, 5 boys with FXS and a diagnosis of autism spectrum disorder (ASD), and 12 CA boys during sentence repetition. Sentences had similar articulation rates in syllables per second as determined acoustically. Four segmental/prosodic factors were used to predict perceived rate: (a) percentage consonants correct, (b) overall fundamental frequency (F(0)) level, (c) sentence-final F(0) drop, and (d) acoustically determined articulation rate with the final word of the sentence excluded. RESULTS: Boys with FXS and ASD were judged to talk faster than CA controls. Multiple linear regression indicated that articulation rate with the final word of the sentence excluded and sentence-final F(0) drop accounted for 91% of the variance for perceived rate. CONCLUSIONS: Descriptions of speakers with FXS as having fast and/or fluctuating articulation rates may be influenced by autism status. Also, atypical sentence-final prosody may be related to perceived rate in boys with FXS and ASD.

Discourse skills of boys with fragile X syndrome in comparison to boys with Down syndrome.

PURPOSE: This study compared the conversational discourse skills of boys who have fragile X syndrome with and without autism spectrum disorder (ASD) with those of boys with Down syndrome and boys who are typically developing. METHOD: Participants were boys who have fragile X syndrome with (n = 26) and without (n = 28) ASD, boys with Down syndrome (n = 29), and boys who are typically developing (n = 22). Turns during an examiner-child interaction consisting of structured and semistructured activities were coded for the boys' ability to maintain a topic of conversation and the frequency of perseveration. RESULTS: The results revealed that boys who had both fragile X and ASD produced significantly more noncontingent discourse than did boys who had only fragile X, boys with Down syndrome, or typically developing boys. This finding was observed regardless of whether the topic was maintained or changed and whether the turn type was a response or initiation. Regardless of autism status, boys with fragile X used more perseveration than did boys in the other groups. CONCLUSION: These findings suggest that some aspects of the conversational discourse difficulties attributed to fragile X syndrome may be a function of the high rate of comorbidity between fragile X and autism, whereas some difficulties may be characteristic of fragile X syndrome.

Articulation rate and vowel space characteristics of young males with fragile X syndrome: preliminary acoustic findings.

PURPOSE: Increased speaking rate is a commonly reported perceptual characteristic among males with fragile X syndrome (FXS). The objective of this preliminary study was to determine articulation rate-one component of perceived speaking rate-and vowel space characteristics of young males with FXS. METHOD: Young males with FXS (n = 38), developmental age (DA)-matched males (n = 21), and chronological age (CA)-matched males (n = 16) were audiotaped while engaged in spontaneous conversation and a picture-naming task. Articulation rate in syllables per second during intelligible utterances and vowel space area/dispersion measures were acoustically determined for each speaker. RESULTS: Males with FXS did not articulate significantly faster than CA-matched males. Area and dispersion of the acoustic vowel space also were similar between the 2 groups. Males with FXS, however, used significantly shorter utterances and had a tendency to pause less often than CA-matched males. In addition, males with FXS exhibited greater intraspeaker variability of formants associated with the vowel /a/. CONCLUSIONS: These preliminary findings suggest that articulation rate may not be a primary factor contributing to perceived speaking rate of males with FXS. Limitations of the study relative to speech production tasks and utterance intelligibility are discussed.