Atypical neural responses to language have been found in toddlers with autism spectrum disorder (
Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder influenced by both genetic and environmental factors. Recently, gut dysbiosis has emerged as a powerful contributor to ASD symptoms. In this study, we recruited over 100 age-matched sibling pairs (between 2 and 8 years old) where one had an Autism ASD diagnosis and the other was developing typically (TD) (432 samples total). We collected stool samples over four weeks, tracked over 100 lifestyle and dietary variables, and surveyed behavior measures related to ASD symptoms. We identified 117 amplicon sequencing variants (ASVs) that were significantly different in abundance between sibling pairs across all three timepoints, 11 of which were supported by at least two contrast methods. We additionally identified dietary and lifestyle variables that differ significantly between cohorts, and further linked those variables to the ASVs they statistically relate to. Overall, dietary and lifestyle features were explanatory of ASD phenotype using logistic regression, however, global compositional microbiome features were not. Leveraging our longitudinal behavior questionnaires, we additionally identified 11 ASVs associated with changes in reported anxiety over time within and across all individuals. Lastly, we find that overall microbiome composition (beta-diversity) is associated with specific ASD-related behavioral characteristics.
more » « less- NSF-PAR ID:
- 10381845
- Publisher / Repository:
- Oxford University Press
- Date Published:
- Journal Name:
- ISME Communications
- Volume:
- 1
- Issue:
- 1
- ISSN:
- 2730-6151
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract ASD ) and in their unaffected siblings. However, given that language difficulties are often seen in these children, it is difficult to interpret whether these neural differences are a result of the diagnosis ofASD or impairments in their language abilities. In this study, we recorded event‐related potentials (ERP s) from four groups of 36‐month‐olds: low‐risk control (LRC ), high risk forASD defined as having an older sibling withASD (HRA ) but who do not haveASD or milder autism‐like symptoms (HRA ‐Typ),HRA children who do not haveASD but exhibit milder autism‐like symptoms (HRA ‐Atyp) andHRA children diagnosed withASD (ASD ). Children listened to words expected to be acquired early (e.g. ball) and words expected to be acquired late (e.g. calf).ERP s were analysed over time windows sensitive to word processing as well as frontal and temporo‐parietal sites over the left and right hemispheres. When controlling for language abilities, there were group differences within the temporo‐parietal sites. Specifically, theHRA ‐Atyp group showed a different timed response to late words compared to theASD andLRC groups. In addition, we found a relation between neural responses in the left frontal sites andASD severity. Our results suggest that both language abilities andASD diagnoses are important to consider when interpreting neural differences in lexical processing. -
Digital Behavioral Phenotyping Detects Atypical Pattern of Facial Expression in Toddlers with Autismmore » « less
Commonly used screening tools for autism spectrum disorder (ASD) generally rely on subjective caregiver questionnaires. While behavioral observation is more objective, it is also expensive, time‐consuming, and requires significant expertise to perform. As such, there remains a critical need to develop feasible, scalable, and reliable tools that can characterize ASD risk behaviors. This study assessed the utility of a tablet‐based behavioral assessment for eliciting and detecting one type of risk behavior, namely, patterns of facial expression, in 104 toddlers (ASD
N = 22) and evaluated whether such patterns differentiated toddlers with and without ASD. The assessment consisted of the child sitting on his/her caregiver's lap and watching brief movies shown on a smart tablet while the embedded camera recorded the child's facial expressions. Computer vision analysis (CVA) automatically detected and tracked facial landmarks, which were used to estimate head position and facial expressions (Positive, Neutral, All Other). Using CVA, specific points throughout the movies were identified that reliably differentiate between children with and without ASD based on their patterns of facial movement and expressions (area under the curves for individual movies ranging from 0.62 to 0.73). During these instances, children with ASD more frequently displayed Neutral expressions compared to children without ASD, who had more All Other expressions. The frequency of All Other expressions was driven by non‐ASD children more often displaying raised eyebrows and an open mouth, characteristic of engagement/interest. Preliminary results suggest computational coding of facial movements and expressions via a tablet‐based assessment can detect differences in affective expression, one of the early, core features of ASD.Lay Summary This study tested the use of a tablet in the behavioral assessment of young children with autism. Children watched a series of developmentally appropriate movies and their facial expressions were recorded using the camera embedded in the tablet. Results suggest that computational assessments of facial expressions may be useful in early detection of symptoms of autism.
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Differences in prosody (e.g., intonation, rhythm) are among the most obvious language‐related impairments in autism spectrum disorder (ASD), and significantly impact communication. Subtle prosodic differences have also been identified in a subset of clinically unaffected first‐degree relatives of individuals with ASD, and may reflect genetic liability to ASD. This study investigated the neural basis of prosodic differences in ASD and first‐degree relatives through analysis of feedforward and feedback control involved in the planning, production, self‐monitoring, and self‐correction of speech by using a pitch‐perturbed auditory feedback paradigm during sustained vowel and speech production. Results revealed larger vocal response magnitudes to pitch‐perturbed auditory feedback across tasks in ASD and ASD parent groups, with differences in sustained vowel production driven by parents who displayed subclinical personality and language features associated with ASD (i.e., broad autism phenotype). Both ASD and ASD parent groups exhibited increased response onset latencies during sustained vowel production, while the ASD parent group exhibited decreased response onset latencies during speech production. Vocal response magnitudes across tasks were associated with prosodic atypicalities in both individuals with ASD and their parents. Exploratory event‐related potential (ERP) analyses in a subgroup of participants during the sustained vowel task revealed reduced P1 ERP amplitudes in the ASD group, with similar trends observed in parents. Overall, results suggest underdeveloped feedforward systems and neural attenuation in detecting audio‐vocal feedback may contribute to ASD‐related prosodic atypicalities. Importantly, results implicate atypical audio‐vocal integration as a marker of genetic risk to ASD, evident in ASD and among clinically unaffected relatives.
Autism Res 2019, 12: 1192–1210Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc.Lay Summary Previous research has identified atypicalities in prosody (e.g., intonation) in individuals with ASD and a subset of their first‐degree relatives. In order to better understand the mechanisms underlying prosodic differences in ASD, this study examined how individuals with ASD and their parents responded to unexpected differences in what they heard themselves say to modify control of their voice (i.e., audio‐vocal integration). Results suggest that disruptions to audio‐vocal integration in individuals with ASD contribute to ASD‐related prosodic atypicalities, and the more subtle differences observed in parents could reflect underlying genetic liability to ASD.
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Abstract Background Repetitive action, resistance to environmental change and fine motor disruptions are hallmarks of autism spectrum disorder (ASD) and other neurodevelopmental disorders, and vary considerably from individual to individual. In animal models, conventional behavioral phenotyping captures such fine-scale variations incompletely. Here we observed male and female C57BL/6J mice to methodically catalog adaptive movement over multiple days and examined two rodent models of developmental disorders against this dynamic baseline. We then investigated the behavioral consequences of a cerebellum-specific deletion in Tsc1 protein and a whole-brain knockout in Cntnap2 protein in mice. Both of these mutations are found in clinical conditions and have been associated with ASD.
Methods We used advances in computer vision and deep learning, namely a generalized form of high-dimensional statistical analysis, to develop a framework for characterizing mouse movement on multiple timescales using a single popular behavioral assay, the open-field test. The pipeline takes virtual markers from pose estimation to find behavior clusters and generate wavelet signatures of behavior classes. We measured spatial and temporal habituation to a new environment across minutes and days, different types of self-grooming, locomotion and gait.
Results Both Cntnap2 knockouts and L7-Tsc1 mutants showed forelimb lag during gait. L7-Tsc1 mutants and Cntnap2 knockouts showed complex defects in multi-day adaptation, lacking the tendency of wild-type mice to spend progressively more time in corners of the arena. In L7-Tsc1 mutant mice, failure to adapt took the form of maintained ambling, turning and locomotion, and an overall decrease in grooming. However, adaptation in these traits was similar between wild-type mice and Cntnap2 knockouts. L7-Tsc1 mutant and Cntnap2 knockout mouse models showed different patterns of behavioral state occupancy.
Limitations Genetic risk factors for autism are numerous, and we tested only two. Our pipeline was only done under conditions of free behavior. Testing under task or social conditions would reveal more information about behavioral dynamics and variability.
Conclusions Our automated pipeline for deep phenotyping successfully captures model-specific deviations in adaptation and movement as well as differences in the detailed structure of behavioral dynamics. The reported deficits indicate that deep phenotyping constitutes a robust set of ASD symptoms that may be considered for implementation in clinical settings as quantitative diagnosis criteria.
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Abstract Olfaction supports a multitude of behaviors vital for social communication and interactions between conspecifics. Intact sensory processing is contingent upon proper circuit wiring. Disturbances in genetic factors controlling circuit assembly and synaptic wiring can lead to neurodevelopmental disorders, such as autism spectrum disorder (ASD), where impaired social interactions and communication are core symptoms. The variability in behavioral phenotype expression is also contingent upon the role environmental factors play in defining genetic expression. Considering the prevailing clinical diagnosis of ASD, research on therapeutic targets for autism is essential. Behavioral impairments may be identified along a range of increasingly complex social tasks. Hence, the assessment of social behavior and communication is progressing towards more ethologically relevant tasks. Garnering a more accurate understanding of social processing deficits in the sensory domain may greatly contribute to the development of therapeutic targets. With that framework, studies have found a viable link between social behaviors, circuit wiring, and altered neuronal coding related to the processing of salient social stimuli. Here, the relationship between social odor processing in rodents and humans is examined in the context of health and ASD, with special consideration for how genetic expression and neuronal connectivity may regulate behavioral phenotypes.more » « less
