Neural responses to affective speech, including motherese, map onto clinical and social eye tracking profiles in toddlers with ASD

Xiao, Yaqiong; Wen, Teresa H.; Kupis, Lauren; Eyler, Lisa T.; Goel, Disha; Vaux, Keith K.; Lombardo, Michael; Lewis, Nathan E.; Pierce, Karen; Courchesne, Eric

doi:10.1038/s41562-021-01237-y

Cited by 23 publications

(25 citation statements)

References 65 publications

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“…Furthermore, given that normative brain charts indicate that cortical thickness tends to peak in early childhood followed by slow decline over the lifespan 80 , and so, these ASD toddler results combined with others in older ASD samples would indicate that increased early developmental cortical thickening combined with attenuated cortical thinning of LH STC may be a robust and key neural feature of ASD neurodevelopment. Given the observations of early developmental functional abnormalities in LH STC for language 33,34,81 , these converging results may implicate that atypical structural development and underlying genomic mechanisms affecting LH STC 34,35 may perturb the ability of this region to develop functional specialization for processes like language and socialcommunication.…”

Section: Discussionmentioning

confidence: 96%

Language and Social Regions Are Affected in Toddlers with Autism and Predict Later Language Outcome

Duan

Eyler

Pierce

et al. 2022

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Autism spectrum disorder is a heterogeneous neurodevelopmental disorder. Early brain overgrowth yet reduced cerebellar size is well recognized for autism, but cortical regions involved show inconsistent patterns of alteration. No complete and replicable map of early regional brain size alterations has been charted. It is also not clear whether individual differences in brain size relate to autism symptom severity and cognitive deficits and predict later language outcomes. We leveraged structural MRI data from 166 autistic and 109 typical developing toddlers to comprehensively and systematically investigate regional gray matter volume alterations and cortical surface area and thickness perturbations in autism compared to typical developing toddlers using linear mixed-effect models. We then examined their replicability in an independent cohort of 38 autistic and 37 typical developing toddlers. We further investigated associations between regional brain size and symptom severity, Mullen and Vineland cognitive performance using linear regression models. Lastly, we investigated whether early brain size (at intake mean age of 2.5 years) can improve support vector machine prediction of language outcome at 3-4 years of age when added to a model containing intake clinical and behavioral measures. Compared to typical developing toddlers, autistic toddlers presented larger or thicker lateral temporal regions, smaller or thinner frontal lobe and midline structures, larger callosal subregion volume, and smaller cerebellum. Most of these differences were replicated in an independent toddler cohort. Moreover, the identified gray matter alterations were related to autism symptom severity and cognitive impairments at intake, and, remarkably, they improved the accuracy for predicting later language outcome beyond intake clinical and demographic variables. Gray matter volume, thickness, and surface area in regions involved in language, social, and face processing were altered in autistic toddlers. Alterations in these regions are major early-age developmental attributes of autism. The early-age alterations in these cortical attributes in different regions may be the result of dysregulation in multiple neural processes and stages, consistent with prenatal multi-process, multi-stage models of autism. Here we also show these gray matter alterations are promising prognostic biomarkers for language outcome prediction.

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Section: Discussionmentioning

confidence: 96%

Language and Social Regions Are Affected in Toddlers with Autism and Predict Later Language Outcome

Duan

Eyler

Pierce

et al. 2022

Preprint

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“…Our data also suggest that the subgroup of the population with ASD and low attention to motherese may be more homogeneous at some intermediate psychobiological level, thereby potentially justifying the use of this test to stratify the population with autism in future studies of social attention and its correlates. A recent study 27 revealed that toddlers with ASD who showed low attention levels to motherese speech as a group had lower levels of neural functional activity in classic speech-processing areas, such as the superior temporal gyrus, compared with other toddlers with ASD who paid greater attention to motherese speech.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…In a brain imaging study, toddlers with ASD who showed the lowest levels of attention to motherese speech also showed the lowest levels of neural functional activation in speech-processing regions and lower language abilities than toddlers who paid greater attention to motherese speech. 27 Eye tracking is a relatively new approach for rapidly and accurately characterizing attention in ASD [28][29][30][31][32][33][34][35][36][37] and holds promise as a screening and diagnostic tool. 31,33 Eye-tracking studies, however, have been largely restricted to the visual domain and have demonstrated reduced attention to social visual images in ASD.…”

Section: Introductionmentioning

confidence: 99%

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Level of Attention to Motherese Speech as an Early Marker of Autism Spectrum Disorder

et al. 2023

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ImportanceCaregivers have long captured the attention of their infants by speaking in motherese, a playful speech style characterized by heightened affect. Reduced attention to motherese in toddlers with autism spectrum disorder (ASD) may be a contributor to downstream language and social challenges and could be diagnostically revealing.ObjectiveTo investigate whether attention toward motherese speech can be used as a diagnostic classifier of ASD and is associated with language and social ability.Design, Setting, and ParticipantsThis diagnostic study included toddlers aged 12 to 48 months, spanning ASD and non-ASD diagnostic groups, at a research center. Data were collected from February 2018 to April 2021 and analyzed from April 2021 to March 2022.ExposuresGaze-contingent eye-tracking test.Main Outcomes and MeasuresUsing gaze-contingent eye tracking wherein the location of a toddler’s fixation triggered a specific movie file, toddlers participated in 1 or more 1-minute eye-tracking tests designed to quantify attention to motherese speech, including motherese vs traffic (ie, noisy vehicles on a highway) and motherese vs techno (ie, abstract shapes with music). Toddlers were also diagnostically and psychometrically evaluated by psychologists. Levels of fixation within motherese and nonmotherese movies and mean number of saccades per second were calculated. Receiver operating characteristic (ROC) curves were used to evaluate optimal fixation cutoff values and associated sensitivity, specificity, positive predictive value (PPV), and negative predictive value. Within the ASD group, toddlers were stratified based on low, middle, or high levels of interest in motherese speech, and associations with social and language abilities were examined.ResultsA total of 653 toddlers were included (mean [SD] age, 26.45 [8.37] months; 480 males [73.51%]). Unlike toddlers without ASD, who almost uniformly attended to motherese speech with a median level of 82.25% and 80.75% across the 2 tests, among toddlers with ASD, there was a wide range, spanning 0% to 100%. Both the traffic and techno paradigms were effective diagnostic classifiers, with large between-group effect sizes (eg, ASD vs typical development: Cohen d, 1.0 in the techno paradigm). Across both paradigms, a cutoff value of 30% or less fixation on motherese resulted in an area under the ROC curve (AUC) of 0.733 (95% CI, 0.693-0.773) and 0.761 (95% CI, 0.717-0.804), respectively; specificity of 98% (95% CI, 95%-99%) and 96% (95% CI, 92%-98%), respectively; and PPV of 94% (95% CI, 86%-98%). Reflective of heterogeneity and expected subtypes in ASD, sensitivity was lower at 18% (95% CI, 14%-22%) and 29% (95% CI, 24%-34%), respectively. Combining metrics increased the AUC to 0.841 (95% CI, 0.805-0.877). Toddlers with ASD who showed the lowest levels of attention to motherese speech had weaker social and language abilities.Conclusions and RelevanceIn this diagnostic study, a subset of toddlers showed low levels of attention toward motherese speech. When a cutoff level of 30% or less fixation on motherese speech was used, toddlers in this range were diagnostically classified as having ASD with high accuracy. Insight into which toddlers show unusually low levels of attention to motherese may be beneficial not only for early ASD diagnosis and prognosis but also as a possible therapeutic target.

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“…However, given that the diagnosis is typically implicitly endowed with a certain type of face validity that most medical diagnoses also possess (e.g., differential biology), many will still assume that the diagnosis should indeed split apart individuals with very different underlying biology behind the phenotype. Evidence has been mounting in recent years suggesting that early language issues are quite important stratifiers, both from a clinical standpoint, but also in terms of underlying biology (3,(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49). At what point should the field reflect back on whether such changes some several decades back were warranted?…”

Section: Back To the Future -The History Of Autismmentioning

confidence: 99%

Rethinking Our Concepts and Assumptions About Autism

Lombardo

Mandelli

2022

Front. Psychiatry

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Autism is a clinical consensus diagnosis made based on behavioral symptoms of early developmental difficulties in domains of social-communication (SC) and restricted repetitive behaviors (RRB). Many readily assume that alongside being optimal for separating individuals based on SC and RRB behavioral domains, that the label should also be highly useful for explaining differential biology, outcomes, and treatment (BOT) responses. However, we also now take for granted the fact that the autism population is vastly heterogeneous at multiple scales, from genome to phenome. In the face of such multi-scale heterogeneity, here we argue that the concept of autism along with the assumptions that surround it require some rethinking. While we should retain the diagnosis for all the good it can do in real-world circumstances, we also call for the allowance of multiple other possible definitions that are better tailored to be highly useful for other translational end goals, such as explaining differential BOT responses.

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Neural responses to affective speech, including motherese, map onto clinical and social eye tracking profiles in toddlers with ASD

Cited by 23 publications

References 65 publications

Language and Social Regions Are Affected in Toddlers with Autism and Predict Later Language Outcome

Language and Social Regions Are Affected in Toddlers with Autism and Predict Later Language Outcome

Level of Attention to Motherese Speech as an Early Marker of Autism Spectrum Disorder

Rethinking Our Concepts and Assumptions About Autism

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