Podcast: A potential biomarker to AID, not MAKE, a diagnosis

The media has just called another biological marker a “diagnostic test”, when in this case, it was always intended to be an aid, not a test itself. It involves using baby hair strands to look a variation in metabolism of certain chemical elements across time. Remarkably, it showed similar results in autistic children in Japan, the US and Sweden. It’s not ready to be used as a diagnostic test, so what is it supposed to do? Listen to an interview with the inventor and researcher, Dr. Manish Arora from The Icahn School of Medicine at Mt. Sinai School here.

The full article (open access) can be found here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9740182/

Children’s ability to share attention with another person (i.e., achieve joint attention) is critical for learning about their environments in general1-3 and supporting language and object word learning in particular.1,4-14 While joint attention (JA) as it pertains to autism spectrum disorder (ASD) is often more narrowly operationalized as arising from eye gaze or explicit pointing cues alone,2,5,10,15-19 recent evidence demonstrates that JA in natural environments can be achieved more broadly through multiple other pathways beyond gaze and gestures.2,4,20-31 Here, we use dual head-mounted eye tracking to examine pathways into and characteristics of JA episodes during free-flowing parent-child toy play, comparing children with ASD to typically developing (TD) children. Moments of JA were defined objectively as both the child’s and parent’s gaze directed to the same object at the same time. Consistent with previous work in TD children,4,21,25,30-32 we found that both TD and ASD children rarely look at their parent’s face in this unstructured free play context. Nevertheless, both groups achieved similarly high rates of JA that far exceeded chance, suggesting the use of alternative pathways into JA. We characterize these alternate pathways, find they occur at similar levels across both groups, and achieve similar ends: namely, for both groups, targets of JA are named more frequently by parents in those moments than non-jointly attended objects. These findings broaden the conceptualization of JA abilities and impairment in ASD and raise questions regarding the mechanistic role of the face-gaze-mediated JA pathway in ASD.

Keywords: autism; development; dyadic interaction; eye tracking; joint attention; naturalistic play; social interaction.

Background: Canonical babbling-producing syllables with a mature consonant, full vowel, and smooth transition-is an important developmental milestone that typically occurs in the first year of life. Some studies indicate delayed or reduced canonical babbling in infants at high familial likelihood for autism spectrum disorder (ASD) or who later receive an ASD diagnosis, but evidence is mixed. More refined characterization of babbling in the first year of life in infants with high likelihood for ASD is needed.

Methods: Vocalizations produced at 6 and 12 months by infants (n = 267) taking part in a longitudinal study were coded for canonical and non-canonical syllables. Infants were categorized as low familial likelihood (LL), high familial likelihood diagnosed with ASD at 24 months (HL-ASD) or not diagnosed (HL-Neg). Language delay was assessed based on 24-month expressive and receptive language scores. Canonical babble ratio (CBR) was calculated by dividing the number of canonical syllables by the number of total syllables. Generalized linear (mixed) models were used to assess the relationship between group membership and CBR, controlling for site, sex, and maternal education. Logistic regression was used to assess whether canonical babbling ratios at 6 and 12 months predict 24-month diagnostic outcome.

Results: No diagnostic group differences in CBR were detected at 6 months, but HL-ASD infants produced significantly lower CBR than both the HL-Neg and LL groups at 12 months. HL-Neg infants with language delay also showed reduced CBR at 12 months. Neither 6- nor 12-month CBR was significant predictors of 24-month diagnostic outcome (ASD versus no ASD) in logistic regression.

Limitations: Small numbers of vocalizations produced by infants at 6 months may limit the reliability of CBR estimates. It is not known if results generalize to infants who are not at high familial likelihood, or infants from more diverse racial and socioeconomic backgrounds.

Conclusions: Lower canonical babbling ratios are apparent by the end of the first year of life in ASD regardless of later language delay, but are also observed for infants with later language delay without ASD. Canonical babbling may lack specificity as an early marker when used on its own.

Parent-focused interventions have been designed to provide training and support to caregivers who are essential in achieving positive outcomes for children with intellectual and developmental disabilities (IDD). In 2020, significant crises, including the COVID-19 pandemic and continued racial tensions, profoundly impacted the livelihood of children with IDD and their families. Many ongoing efforts to address disparities among this population were halted temporarily and required further adaptations. Researchers adapted interventions and support to address the disparities impacting children with IDD and their families with limited guidance. We provide a descriptive case analysis of four parent-focused interventions that responded to the global crises to continue serving children with IDD and their families. The four distinct programs were based on applied behavior analysis and naturalistic, developmental-behavioral paradigms that were culturally adapted for families of young children with IDD from diverse cultural and socioeconomic backgrounds. We present the qualitative reports on the challenges and benefits that arose with adapting the four parent-focused interventions for telehealth implementation. We focused specifically on adaptations made in recruitment and retention, instrumentation and measurement, research staff training, and intervention delivery. We synthesize our experience with challenges and solutions in adapting parent-focused interventions for racially/ethnically and socioeconomically diverse children with IDD and their families. We conclude with recommendations for researchers and practitioners on methods for adapting parent-focused interventions to address the significant health disparities that impact racially, ethnically, and socioeconomically diverse children with IDD and their families.

Keywords: COVID-19; autism; intellectual disability; parent-focused interventions; practice; racial/ethnic diversity.

While previous work has identified the early predictors of language skills in infants at elevated familial risk (ER) and low familial risk (LR) for autism spectrum disorder (ASD), no studies to date have explored whether these predictors vary based on diagnostic outcome of ASD or no ASD. The present study used a large, multisite dataset to examine associations between a set of commonly studied predictor variables (infant gesture abilities, fine motor skills, nonverbal cognition, and maternal education level), measured at 12 months, and language skills, measured at 3 years, across three diagnostic outcome groups-infants with ASD (“ASD”), ER infants without ASD (“ER-no ASD”), and LR infants without ASD (“LR-no ASD”). Findings revealed that the predictors of language skills differed across groups, as gesture abilities were positively associated with language skills in the ER-no ASD group but negatively associated with language skills in the ASD group. Furthermore, maternal education level was positively associated with language skills in the ASD and LR-no ASD groups only. Variability in these early predictors may help explain why language skills are heterogeneous across the autism spectrum, and, with further study, may help clinicians identify those in need of additional and/or specialized intervention services that support language development. LAY SUMMARY: The present study identified predictors of language skills in infants with and without autism spectrum disorder (ASD). Maternal education level and 12-month gesture abilities predicted 3-year language skills in infants with ASD. Measuring these predictors early in life may help identify infants and families in need of additional and/or specialized intervention services that support language development.

Keywords: gesture; infant sibling; language; maternal education; motor; nonverbal cognition.

Assessment of autism spectrum disorder (ASD) relies on expert clinician observation and judgment, but objective measurement tools have the potential to provide additional information on ASD symptom severity. Diagnostic evaluations for ASD typically include the autism diagnostic observation schedule (ADOS-2), a semi-structured assessment composed of a series of social presses. The current study examined associations between concurrent objective features of child vocalizations during the ADOS-2 and examiner-rated autism symptom severity. The sample included 66 children (49 male; M = 40 months, SD = 10.58) evaluated in a university-based clinic, 61 of whom received an ASD diagnosis. Research reliable administration of the ADOS-2 provided social affect (SA) and restricted and repetitive behavior (RRB) calibrated severity scores (CSS). Audio was recorded from examiner-worn eyeglasses during the ADOS-2 and child and adult speech were differentiated with LENA SP Hub. PRAAT was used to ascertain acoustic features of the audio signal, specifically the mean fundamental vocal frequency (F0) of LENA-identified child speech-like vocalizations (those with phonemic content), child cry vocalizations, and adult speech. Sphinx-4 was employed to estimate child and adult phonological features indexed by the average consonant and vowel count per vocalization. More than a quarter of the variance in ADOS-2 RRB CSS was predicted by the combination of child phoneme count per vocalization and child vocalization F0. Findings indicate that both acoustic and phonological features of child vocalizations are associated with expert clinician ratings of autism symptom severity. LAY SUMMARY: Determination of the severity of autism spectrum disorder is based in part on expert (but subjective) clinician observations during the ADOS-2. Two characteristics of child vocalizations-a smaller number of speech-like sounds per vocalization and higher pitched vocalizations (including cries)-were associated with greater autism symptom severity. The results suggest that objectively ascertained characteristics of children’s vocalizations capture variance in children’s restricted and repetitive behaviors that are reflected in clinician severity indices.

Keywords: audio processing; objective measurement; vocalization.

Background

Autism spectrum disorder (ASD) is a neurodevelopmental disorder diagnosed based on social impairment, restricted interests, and repetitive behaviors. Contemporary theories posit that cerebellar pathology contributes causally to ASD by disrupting error-based learning (EBL) during infancy. The present study represents the first test of this theory in a prospective infant sample, with potential implications for ASD detection.

Methods

Data from the Infant Brain Imaging Study (n = 94, 68 male) were used to examine 6-month cerebellar functional connectivity magnetic resonance imaging in relation to later (12/24-month) ASD-associated behaviors and outcomes. Hypothesis-driven univariate analyses and machine learning–based predictive tests examined cerebellar–frontoparietal network (FPN; subserves error signaling in support of EBL) and cerebellar–default mode network (DMN; broadly implicated in ASD) connections. Cerebellar-FPN functional connectivity was used as a proxy for EBL, and cerebellar-DMN functional connectivity provided a comparative foil. Data-driven functional connectivity magnetic resonance imaging enrichment examined brain-wide behavioral associations, with post hoc tests of cerebellar connections.

Results

Cerebellar-FPN and cerebellar-DMN connections did not demonstrate associations with ASD. Functional connectivity magnetic resonance imaging enrichment identified 6-month correlates of later ASD-associated behaviors in networks of a priori interest (FPN, DMN), as well as in cingulo-opercular (also implicated in error signaling) and medial visual networks. Post hoc tests did not suggest a role for cerebellar connections.

Conclusions

We failed to identify cerebellar functional connectivity–based contributions to ASD. However, we observed prospective correlates of ASD-associated behaviors in networks that support EBL. Future studies may replicate and extend network-level positive results, and tests of the cerebellum may investigate brain-behavior associations at different developmental stages and/or using different neuroimaging modalities.

Background: Differences in face processing in individuals with ASD is hypothesized to impact the development of social communication skills. This study aimed to characterize the neural correlates of face processing in 12-month-old infants at familial risk of developing ASD by (1) comparing face-sensitive event-related potentials (ERP) (Nc, N290, P400) between high-familial-risk infants who develop ASD (HR-ASD), high-familial-risk infants without ASD (HR-NoASD), and low-familial-risk infants (LR), and (2) evaluating how face-sensitive ERP components are associated with development of social communication skills.

Methods: 12-month-old infants participated in a study in which they were presented with alternating images of their mother’s face and the face of a stranger (LR = 45, HR-NoASD = 41, HR-ASD = 24) as EEG data were collected. Parent-reported and laboratory-observed social communication measures were obtained at 12 and 18 months. Group differences in ERP responses were evaluated using ANOVA, and multiple linear regressions were conducted with maternal education and outcome groups as covariates to assess relationships between ERP and behavioral measures.

Results: For each of the ERP components (Nc [negative-central], N290, and P400), the amplitude difference between mother and stranger (Mother-Stranger) trials was not statistically different between the three outcome groups (Nc p = 0.72, N290 p = 0.88, P400 p = 0.91). Marginal effects analyses found that within the LR group, a greater Nc Mother-Stranger response was associated with better expressive language skills on the Mullen Scales of Early Learning, controlling for maternal education and outcome group effects (marginal effects dy/dx = 1.15; p < 0.01). No significant associations were observed between the Nc and language or social measures in HR-NoASD or HR-ASD groups. In contrast, specific to the HR-ASD group, amplitude difference between the Mother versus Stranger P400 response was positively associated with expressive (dy/dx = 2.1, p < 0.001) and receptive language skills at 12 months (dy/dx = 1.68, p < 0.005), and negatively associated with social affect scores on the Autism Diagnostic Observation Schedule (dy/dx = – 1.22, p < 0.001) at 18 months.

Conclusions: In 12-month-old infant siblings with subsequent ASD, increased P400 response to Mother over Stranger faces is positively associated with concurrent language and future social skills.

In this study we investigated the impact of parental language input on language development and associated neuroscillatory patterns in toddlers at risk of Autism Spectrum Disorder (ASD). Forty-six mother-toddler dyads at either high (n = 22) or low (n = 24) familial risk of ASD completed a longitudinal, prospective study including free-play, resting electroencephalography, and standardized language assessments. Input quantity/quality at 18 months positively predicted expressive language at 24 months, and relationships were stronger for high-risk toddlers. Moderated mediations revealed that input-language relationships were explained by 24-month frontal and temporal gamma power (30-50 Hz) for high-risk toddlers who would later develop ASD. Results suggest that high-risk toddlers may be cognitively and neurally more sensitive to their language environments, which has implications for early intervention.

Keywords: Autism; EEG; Early experience; Language development; Language input.

Autism Spectrum Disorder (ASD) is diagnosed three to four times more frequently in males than in females. Genetic studies of rare variants support a female protective effect (FPE) against ASD. However, sex differences in common inherited genetic risk for ASD are less studied, particularly within families. Leveraging the Danish iPSYCH resource, we found siblings of female ASD cases (n = 1,707) had higher rates of ASD than siblings of male ASD cases (n = 6,270; p < 1.0 × 10−10). In the Simons Simplex and SPARK collections, mothers of ASD cases (n = 7,436) carried more polygenic risk for ASD than fathers of ASD cases (n = 5,926; 0.08 polygenic risk score [PRS] SD; p = 7.0 × 10−7). Further, male unaffected siblings under-inherited polygenic risk (n = 1,519; p = 0.03). Using both epidemiologic and genetic approaches, our findings strongly support an FPE against ASD’s common inherited influences.

This week’s podcast explores the question about whether or not it is beneficial or just confusing to teach your child with autism multiple languages, or suppress the use of more than one language at home. Turns out, being bilingual helps with executive functioning (or those with preserved executive functioning can be bilingual), language, and provides benefits in verbal IQ depending on SES. In other words, it’s not harmful, it can be helpful, and those who choose to speak two languages at home should continue to do so if they feel that it is enhancing their child’s learning. Listen to the podcast here and find more information in the links below:

https://pubmed.ncbi.nlm.nih.gov/35102760/

https://pubmed.ncbi.nlm.nih.gov/34813032/

https://pubmed.ncbi.nlm.nih.gov/36222993/