Publications by authors named "Annette Estes"

115 Publications

Infant vocalizing and phenotypic outcomes in autism: Evidence from the first 2 years.

Child Dev 2021 Oct 28. Epub 2021 Oct 28.

Center for Autism Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Infant vocalizations are early-emerging communicative markers shown to be atypical in autism spectrum disorder (ASD), but few longitudinal, prospective studies exist. In this study, 23,850 infant vocalizations from infants at low (LR)- and high (HR)-risk for ASD (HR-ASD = 23, female = 3; HR-Neg = 35, female = 13; LR = 32, female = 10; 80% White; collected from 2007 to 2017 near Philadelphia) were analyzed at 6, 12, and 24 months. At 12 months, HR-ASD infants produced fewer vocalizations than HR-Neg infants. From 6 to 24 months, HR-Neg infants demonstrated steeper vocalization growth compared to HR-ASD and LR infants. Finally, among HR infants, vocalizing at 12 months was associated with language, social phenotype, and diagnosis at age 2. Infant vocalizing is an objective behavioral marker that could facilitate earlier detection of ASD.
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http://dx.doi.org/10.1111/cdev.13697DOI Listing
October 2021

Pre-symptomatic intervention for autism spectrum disorder (ASD): defining a research agenda.

J Neurodev Disord 2021 10 15;13(1):49. Epub 2021 Oct 15.

Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC, USA.

Autism spectrum disorder (ASD) impacts an individual's ability to socialize, communicate, and interact with, and adapt to, the environment. Over the last two decades, research has focused on early identification of ASD with significant progress being made in understanding the early behavioral and biological markers that precede a diagnosis, providing a catalyst for pre-symptomatic identification and intervention. Evidence from preclinical trials suggest that intervention prior to the onset of ASD symptoms may yield more improved developmental outcomes, and clinical studies suggest that the earlier intervention is administered, the better the outcomes. This article brings together a multidisciplinary group of experts to develop a conceptual framework for behavioral intervention, during the pre-symptomatic period prior to the consolidation of symptoms into diagnosis, in infants at very-high-likelihood for developing ASD (VHL-ASD). The overarching goals of this paper are to promote the development of new intervention approaches, empirical research, and policy efforts aimed at VHL-ASD infants during the pre-symptomatic period (i.e., prior to the consolidation of the defining features of ASD).
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http://dx.doi.org/10.1186/s11689-021-09393-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8520312PMC
October 2021

Longitudinal Prediction of Infant MR Images With Multi-Contrast Perceptual Adversarial Learning.

Front Neurosci 2021 9;15:653213. Epub 2021 Sep 9.

Department of Psychiatry, UNC School of Medicine, University of North Carolina, Chapel Hill, NC, United States.

The infant brain undergoes a remarkable period of neural development that is crucial for the development of cognitive and behavioral capacities (Hasegawa et al., 2018). Longitudinal magnetic resonance imaging (MRI) is able to characterize the developmental trajectories and is critical in neuroimaging studies of early brain development. However, missing data at different time points is an unavoidable occurrence in longitudinal studies owing to participant attrition and scan failure. Compared to dropping incomplete data, data imputation is considered a better solution to address such missing data in order to preserve all available samples. In this paper, we adapt generative adversarial networks (GAN) to a new application: longitudinal image prediction of structural MRI in the first year of life. In contrast to existing medical image-to-image translation applications of GANs, where inputs and outputs share a very close anatomical structure, our task is more challenging as brain size, shape and tissue contrast vary significantly between the input data and the predicted data. Several improvements over existing GAN approaches are proposed to address these challenges in our task. To enhance the realism, crispness, and accuracy of the predicted images, we incorporate both a traditional voxel-wise reconstruction loss as well as a perceptual loss term into the adversarial learning scheme. As the differing contrast changes in T1w and T2w MR images in the first year of life, we incorporate multi-contrast images leading to our proposed 3D multi-contrast perceptual adversarial network (MPGAN). Extensive evaluations are performed to assess the qualityand fidelity of the predicted images, including qualitative and quantitative assessments of the image appearance, as well as quantitative assessment on two segmentation tasks. Our experimental results show that our MPGAN is an effective solution for longitudinal MR image data imputation in the infant brain. We further apply our predicted/imputed images to two practical tasks, a regression task and a classification task, in order to highlight the enhanced task-related performance following image imputation. The results show that the model performance in both tasks is improved by including the additional imputed data, demonstrating the usability of the predicted images generated from our approach.
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http://dx.doi.org/10.3389/fnins.2021.653213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458966PMC
September 2021

A review of executive functioning challenges and strengths in autistic adults.

Clin Neuropsychol 2021 Sep 9:1-32. Epub 2021 Sep 9.

Department of Speech and Hearing Sciences, University of Washington, Seattle, WA, USA.

There has been a steady rise in research characterizing executive functioning (EF) impairments in autistic individuals but limited research investigating EF strengths. This review provides a summary of current EF research in autistic adults with a focus on EF challenges and strengths and potential sources of heterogeneity in research findings. New avenues for addressing gaps in our understanding of EF strengths are proposed. A review of the EF literature was conducted. One hundred twenty-four studies of inhibition, working memory, cognitive flexibility, fluency, planning, decision-making, and subjective measures of EF in autistic adults were included. Autistic adults with average intellectual functioning demonstrate difficulties with cognitive flexibility, phonemic fluency, and working memory. Strengths in planning, decision-making, and semantic verbal fluency were evident in some but not all studies. Findings regarding inhibition are inconclusive. Key findings across each EF domain are discussed and sources of potential heterogeneity across studies were evaluated. The type of measure used appears to contribute to heterogeneous findings. Subjective EF measures revealed more consistent findings of deficits in autistic adults than objective EF measures. Research reveals areas of EF weaknesses as well as strengths in autistic adults. Unlike EF challenges, EF strengths are not well understood. Future research identifying EF strengths is needed to improve services and supports for autistic adults. Further investigation of potential factors that interact with or constrain EF such as comorbid disorders, verbal ability, sensory processing, and other factors specific to autism will be critical to move the field forward and increase understanding of how EF is related to everyday functioning in autistic adults.
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http://dx.doi.org/10.1080/13854046.2021.1971767DOI Listing
September 2021

The Early Start Denver Model Intervention and Mu Rhythm Attenuation in Autism Spectrum Disorders.

J Autism Dev Disord 2021 Jul 26. Epub 2021 Jul 26.

Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.

We examined the relationship between the Early start Denver model (ESDM) intervention and mu rhythm attenuation, an EEG paradigm reflecting neural processes associated with action perception and social information processing. Children were assigned to either receive comprehensive ESDM intervention for two years, or were encouraged to pursue resources in the community. Two years after intervention, EEG was collected during the execution and observation of grasping actions performed by familiar and unfamiliar agents. The ESDM group showed significantly greater attenuation when viewing a parent or caregiver executing a grasping action, compared with an unfamiliar individual executing the same action. Our findings suggest that the ESDM may have a unique impact on neural circuitry underlying social cognition and familiarity.
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http://dx.doi.org/10.1007/s10803-021-05190-7DOI Listing
July 2021

Social and non-social sensory responsivity in toddlers at high-risk for autism spectrum disorder.

Autism Res 2021 10 19;14(10):2143-2155. Epub 2021 Jun 19.

University of Minnesota, Minneapolis, Minnesota, USA.

Empirical evidence concerning sensory responsivity in young children who later develop autism spectrum disorder (ASD) remains relatively limited. It is unclear whether specific patterns or aspects of sensory responsivity underlay the emergence of the disorder. The goals of this study were to (a) examine whether social versus non-social context impacted the expression of sensory responsivity in infants at high risk for ASD, and (b) examine if sensory responsivity in social or non-social contexts was associated with severity of ASD symptoms. The Sensory Experiences Questionnaire 2.1 was collected for 338 infants (131 females, 207 males) at high-risk for ASD at 12 and/or 24 months of age. High-risk toddlers meeting diagnostic criteria for ASD (n = 75) showed elevated sensory responsivity in both social and non-social contexts at 12 months of age and differences widened over the second year of life. Individuals with ASD demonstrate higher responsivity in both contexts suggestive of generalized atypical sensory responsivity in ASD. LAY SUMMARY: Behaviors such as avoiding or noticing sensory input (e.g., sounds, touches) are often different in individuals with autism spectrum disorder (ASD) than those without. The reason for this is widely unknown. The findings from this study show that in toddlers, sensory responsivity increased in both social and non-social situations. Therefore, the setting of sensory input does not explain these differences.
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http://dx.doi.org/10.1002/aur.2556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487998PMC
October 2021

Cataloguing and characterizing interests in typically developing toddlers and toddlers who develop ASD.

Autism Res 2021 08 22;14(8):1710-1723. Epub 2021 May 22.

Institute of Child Development, University of Minnesota, Minneapolis, Minnesota, USA.

Intense interests are common in children with and without autism spectrum disorder (ASD), and little research has characterized aspects of interests that are unique to or shared among children with and without ASD. We aimed to characterize interests in a sample of infants at high-familial-risk (HR) and low-familial-risk (LR) for ASD using a novel interview. Participants included HR siblings who were diagnosed with ASD at 24 months (HR-ASD, n = 56), HR siblings who did not receive an ASD diagnosis at 24 months (HR-Neg, n = 187), and a LR comparison group (n = 109). We developed and collected data with the Intense Interests Inventory at 18- and 24-months of age, a semi-structured interview that measures intensity and peculiarity of interests in toddlers and preschool-aged children. Intensity of interests differed by familial risk at 24 months, with HR-ASD and HR-Neg groups demonstrating equivalent intensity of interests that were higher than the LR group. By contrast, peculiarity of interest differed by ASD diagnosis, with the HR-ASD group showing more peculiar interests than the HR-Neg and LR groups at 24 months. At 18 months the HR-ASD group had more peculiar interests than the LR group, though no differences emerged in intensity of interests. This measure may be useful in identifying clinically-relevant features of interests in young children with ASD. We also replicated previous findings of males showing more intense interests at 18 months in our non-ASD sample. These results reveal new information about the nature of interests and preoccupations in the early autism phenotype. LAY SUMMARY: Intense interests are common in young children with autism and their family members. Intense interests are also prevalent among typically-developing children, and especially boys. Here we catalog interests and features of these interests in a large sample of toddlers enriched for autism risk. Children who had family members with autism had more intense interests, and those who developed autism themselves had more unusual interests at 24 months. These results highlight the importance of different aspects of interest in autism.
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http://dx.doi.org/10.1002/aur.2543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714188PMC
August 2021

Auditory Attention Deployment in Young Adults with Autism Spectrum Disorder.

J Autism Dev Disord 2021 May 19. Epub 2021 May 19.

Institute for Learning and Brain Sciences, University of Washington, Box 357988, Seattle, WA, 98195, USA.

Difficulty listening in noisy environments is a common complaint of individuals with autism spectrum disorder (ASD). However, the mechanisms underlying such auditory processing challenges are unknown. This preliminary study investigated auditory attention deployment in adults with ASD. Participants were instructed to maintain or switch attention between two simultaneous speech streams in three conditions: location (co-located versus ± 30° separation), voice (same voice versus male-female contrast), and both cues together. Results showed that individuals with ASD can selectively direct attention using location or voice cues, but performance was best when both cues were present. In comparison to neurotypical adults, overall performance was less accurate across all conditions. These findings warrant further investigation into auditory attention deployment differences in individuals with ASD.
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http://dx.doi.org/10.1007/s10803-021-05076-8DOI Listing
May 2021

Variability in Responding to Joint Attention Cues in the First Year is Associated With Autism Outcome.

J Am Acad Child Adolesc Psychiatry 2021 Jun 2. Epub 2021 Jun 2.

University of Minnesota, Minneapolis. Electronic address:

Objective: With development, infants become increasingly responsive to the many attention-sharing cues of adults; however, little work has examined how this ability emerges in typical development or in the context of early autism spectrum disorder (ASD). This study characterized variation in the type of cue needed to elicit a response to joint attention (RJA) using the Dimensional Joint Attention Assessment (DJAA) during naturalistic play.

Method: We measured the average redundancy of cue type required for infants to follow RJA bids from an experimenter, as well as their response consistency, in 268 infants at high (HR, n = 68) and low (LR, N = 200) familial risk for ASD. Infants were assessed between 8 and 18 months of age and followed up with developmental and clinical assessments at 24 or 36 months. Our sample consisted of LR infants, as well as HR infants who did (HR-ASD) and did not (HR-neg) develop ASD at 24 months.

Results: We found that HR and LR infants developed abilities to respond to less redundant (more sophisticated) RJA cues at different rates, and that HR-ASD infants displayed delayed abilities, identifiable as early as 9 months, compared to both HR-neg and LR infants. Interestingly, results suggest that HR-neg infants may exhibit a propensity to respond to less redundant (more sophisticated) RJA cues relative to both HR-ASD and LR infants.

Conclusions: Using an approach to characterize variable performance of RJA cue-reading abilities, findings from this study enhance our understanding of both typical and ASD-related proficiencies and deficits in RJA development.
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http://dx.doi.org/10.1016/j.jaac.2021.03.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8636536PMC
June 2021

Relations of Restricted and Repetitive Behaviors to Social Skills in Toddlers with Autism.

J Autism Dev Disord 2021 May 6. Epub 2021 May 6.

University of Minnesota, 56 East River Road, Minneapolis, MN, 55455, USA.

We examined the relations of restricted and repetitive behaviors (RRB; insistence on sameness, repetitive sensory-motor, self-injurious behavior) to social skills overall and aspects that comprise social skills as measured by the VABS-II (coping skills, play/leisure time, interpersonal relationships) in 24- (n = 63) and 36-month old (n = 35), high-familial-risk toddlers with ASD. Hierarchical linear regression results indicated that repetitive sensory-motor was the best predictor of social skills overall. Secondary results indicated that all three RRB subtypes were associated with each subdomain of social skills; however, repetitive sensory-motor was the strongest and most consistent among these effects. While our results suggests a general negative relation of subtypes of RRB to aspects of adaptive social function, repetitive sensory-motor behaviors may be of particular relevance to the development of social skills during toddlerhood.
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http://dx.doi.org/10.1007/s10803-021-05014-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571122PMC
May 2021

The effect of early autism intervention on parental sense of efficacy in a randomized trial depends on the initial level of parent stress.

Autism 2021 10 16;25(7):1924-1934. Epub 2021 Apr 16.

University of California, Davis, USA.

Lay Abstract: This is a study of the secondary effects of interventions for young children with autism on their parents. Specifically, we were interested in the impact on parent's sense of efficacy, or how confident and competent a parent feels about themselves as a parent. We tested three ideas: (1) that the style of the intervention, whether it was more or less structured and whether the parent had a more or less formal role, would impact a parent's sense of efficacy; (2) that the intensity of the intervention, how many hours per week the intervention was delivered, would impact parental efficacy; and (3) that the parent's level of stress prior to intervention would impact how intensity and style effected efficacy. We randomly assigned 87 children with autism, age 13-30 months, into one of four conditions: 15 versus 25 intervention hours crossed with two different styles of intervention. We used statistical tests to examine these ideas. We found that parental efficacy was related to intervention intensity but not style. Parents with higher stress at the beginning of a 1-year, home-based, comprehensive intervention program had a higher sense of parenting efficacy if their child received intensity intervention; parents with lower stress at baseline had a higher sense of efficacy if their child received intervention. If a parent can emerge from the process of diagnosis and early intervention with an increased sense that they can make a difference in their child's life (i.e. increased sense of efficacy), it may set the stage for meeting the long-term demands of parenting a child with autism.
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http://dx.doi.org/10.1177/13623613211005613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418992PMC
October 2021

Presymptomatic Detection and Intervention for Autism Spectrum Disorder.

Pediatrics 2021 05 14;147(5). Epub 2021 Apr 14.

Treuman Katz Center for Pediatric Bioethics, Seattle Children's Research Institute, Seattle, Washington.

Universal screening for autism spectrum disorder (ASD) is recommended during pediatric primary care visits in the first 2 years of life. However, many children are missed by initial screening and not diagnosed with ASD until years later. Research efforts are underway to develop and evaluate new objective measures of risk for ASD that can be used in infancy, before symptoms emerge. Initial studies with these tests, particularly MRI-based screening for infants at high familial risk, have shown promise but have not yet been evaluated in clinical trials. We present the study design for a hypothetical clinical trial that would combine presymptomatic detection and intervention for ASD and consider, through commentaries from diverse perspectives, the ethical issues that should be anticipated in advance of beginning such trials. Commentators Drs Pruett and Piven address the social value of the proposed research and importance of researcher-bioethicist collaborations. Drs Estes and Wolff discuss the clinical potential and challenges of developing presymptomatic interventions for infants at risk for ASD. Dr Harrington takes a neurodiversity view of presymptomatic prediction and intervention and their implications for autistic identity and quality of life. Finally, Drs MacDuffie, Peay and Wilfond consider the potential risks and benefits that must be evaluated and weighed in the next phases of research on presymptomatic detection and intervention for ASD.
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http://dx.doi.org/10.1542/peds.2020-032250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085996PMC
May 2021

Diagnostic shifts in autism spectrum disorder can be linked to the fuzzy nature of the diagnostic boundary: a data-driven approach.

J Child Psychol Psychiatry 2021 10 7;62(10):1236-1245. Epub 2021 Apr 7.

Center for Autism Research, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Background: Diagnostic shifts at early ages may provide invaluable insights into the nature of separation between autism spectrum disorder (ASD) and typical development. Recent conceptualizations of ASD suggest the condition is only fuzzily separated from non-ASD, with intermediate cases between the two. These intermediate cases may shift along a transition region over time, leading to apparent instability of diagnosis.

Methods: We used a cohort of children with high ASD risk, by virtue of having an older sibling with ASD, assessed at 24 months (N = 212) and 36 months (N = 191). We applied machine learning to empirically characterize the classification boundary between ASD and non-ASD, using variables quantifying developmental and adaptive skills. We computed the distance of children to the classification boundary.

Results: Children who switched diagnostic labels from 24 to 36 months, in both directions, (dynamic group) had intermediate phenotypic profiles. They were closer to the classification boundary compared to children who had stable diagnoses, both at 24 months (Cohen's d = .52) and at 36 months (d = .75). The magnitude of change in distance between the two time points was similar for the dynamic and stable groups (Cohen's d = .06), and diagnostic shifts were not associated with a large change. At the individual level, a few children in the dynamic group showed substantial change.

Conclusions: Our results suggested that a diagnostic shift was largely due to a slight movement within a transition region between ASD and non-ASD. This fact highlights the need for more vigilant surveillance and intervention strategies. Young children with intermediate phenotypes may have an increased susceptibility to gain or lose their diagnosis at later ages, calling attention to the inherently dynamic nature of early ASD diagnoses.
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http://dx.doi.org/10.1111/jcpp.13406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8601115PMC
October 2021

Stability of Vocal Variables Measured During the Early Communication Indicator for Children With Autism Spectrum Disorder.

Am J Intellect Dev Disabil 2021 03;126(2):142-157

Sally J. Rogers, University of California, Davis.

The Early Communication Indicator (ECI) was designed to measure expressive communication progress in young children. We evaluated using the 6-min ECI procedure for a new purpose-a sampling context for stable measures of vocal development of young children with autism spectrum disorder (ASD). We evaluated how many ECI sessions were required to adequately stabilize estimates of volubility, communicative use, and phonological complexity of vocalizations at two periods (average of 10 months apart). Participants included 83 young children with ASD (M age = 23.33 months). At study initiation, two phonological complexity variables required two sessions; other variables required three. At study endpoint, all variables required fewer sessions. Findings support the feasibility and stability of using the ECI for the new purpose.
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http://dx.doi.org/10.1352/1944-7558-126.2.142DOI Listing
March 2021

The Ethics of Predicting Autism Spectrum Disorder in Infancy.

J Am Acad Child Adolesc Psychiatry 2021 08 19;60(8):942-945. Epub 2021 Jan 19.

University of Washington, Seattle; Treuman Katz Center for Pediatric Bioethics, Seattle Children's Research Institute, Washington.

Toward the end of a routine check-in appointment with your young patient-a 3-year-old boy recently diagnosed with autism spectrum disorder (ASD)-his mother shares concerns about his infant sister, currently 6 months old. The mother is aware that her daughter is at increased risk for ASD. She requests a magnetic resonance imaging (MRI) scan of her infant's brain, based on research she has read showing that MRI can be used to predict which infants will go on to develop ASD. The mother communicates that she is eager to know whether her daughter is going to develop autism so that she and her husband can prepare financially, and so she can place her daughter on the long waitlist for autism-specific services in her local community. As this family's psychiatrist, how should you respond to her request?
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http://dx.doi.org/10.1016/j.jaac.2021.01.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8629367PMC
August 2021

Towards a Data-Driven Approach to Screen for Autism Risk at 12 Months of Age.

J Am Acad Child Adolesc Psychiatry 2021 08 5;60(8):968-977. Epub 2020 Nov 5.

Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill.

Objective: This study aimed to develop a classifier for infants at 12 months of age based on a parent-report measure (the First Year Inventory 2.0 [FYI]), for the following reasons: (1) to classify infants at elevated risk, above and beyond that attributable to familial risk status for ASD; and (2) to serve as a starting point to refine an approach for risk estimation in population samples.

Method: A total of 54 high-familial risk (HR) infants later diagnosed with ASD (HR-ASD), 183 HR infants not diagnosed with ASD at 24 months of age (HR-Neg), and 72 low-risk controls participated in the study. All infants contributed FYI data at 12 months of age and had a diagnostic assessment for ASD at age 24 months. A data-driven, cross-validated analytic approach was used to develop a classifier to determine screening accuracy (eg, sensitivity) of the FYI to classify HR-ASD and HR-Neg.

Results: The newly developed FYI classifier had an estimated sensitivity of 0.71 (95% CI: 0.50, 0.91) and specificity of 0.72 (95% CI: 0.49, 0.91).

Conclusion: This classifier demonstrates the potential to improve current screening for ASD risk at 12 months of age in infants already at elevated familial risk for ASD, increasing opportunities for detection of autism risk in infancy. Findings from this study highlight the utility of combining parent-report measures with machine learning approaches.
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http://dx.doi.org/10.1016/j.jaac.2020.10.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127075PMC
August 2021

A Novel Method for High-Dimensional Anatomical Mapping of Extra-Axial Cerebrospinal Fluid: Application to the Infant Brain.

Front Neurosci 2020 2;14:561556. Epub 2020 Oct 2.

Department of Computer Science, University of North Carolina, Chapel Hill, NC, United States.

Cerebrospinal fluid (CSF) plays an essential role in early postnatal brain development. Extra-axial CSF (EA-CSF) volume, which is characterized by CSF in the subarachnoid space surrounding the brain, is a promising marker in the early detection of young children at risk for neurodevelopmental disorders. Previous studies have focused on global EA-CSF volume across the entire dorsal extent of the brain, and not regionally-specific EA-CSF measurements, because no tools were previously available for extracting local EA-CSF measures suitable for localized cortical surface analysis. In this paper, we propose a novel framework for the localized, cortical surface-based analysis of EA-CSF. The proposed processing framework combines probabilistic brain tissue segmentation, cortical surface reconstruction, and streamline-based local EA-CSF quantification. The quantitative analysis of local EA-CSF was applied to a dataset of typically developing infants with longitudinal MRI scans from 6 to 24 months of age. There was a high degree of consistency in the spatial patterns of local EA-CSF across age using the proposed methods. Statistical analysis of local EA-CSF revealed several novel findings: several regions of the cerebral cortex showed reductions in EA-CSF from 6 to 24 months of age, and specific regions showed higher local EA-CSF in males compared to females. These age-, sex-, and anatomically-specific patterns of local EA-CSF would not have been observed if only a global EA-CSF measure were utilized. The proposed methods are integrated into a freely available, open-source, cross-platform, user-friendly software tool, allowing neuroimaging labs to quantify local extra-axial CSF in their neuroimaging studies to investigate its role in typical and atypical brain development.
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http://dx.doi.org/10.3389/fnins.2020.561556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561674PMC
October 2020

Interaction of Treatment Intensity and Autism Severity on Frequency and Maturity of Spontaneous Communication in Toddlers with Autism Spectrum Disorder.

Autism Res 2020 11 24;13(11):1902-1912. Epub 2020 Oct 24.

Huntington Beach, California, USA.

This study tested whether the effect of treatment intensity or treatment style on children's frequency and maturity of spontaneous communication varied by initial severity of disability. Eighty-seven toddlers with autism spectrum disorders were randomly assigned to either (a) 15 hrs per week of discrete trial teaching (DTT), (b) 25 hrs per week of DTT, (c) 15 hrs per week of a naturalistic developmental behavioral intervention (NDBI), or (d) 25 hrs per week of NDBI. Trained research staff implemented the 1:1 treatments in homes or educational centers over 12 months. We quantified the frequency and maturity of spontaneous communication during monthly 6-min communication samples. We quantified disability severity at Time 1 using the developmental quotient from the Mullen Scales of Early Learning and the total calibrated severity score from the Autism Diagnostic Observation Schedule-second edition. Higher levels of treatment intensity (i.e., more hours per week) benefited frequency and maturity of spontaneous communication growth rate only in children with relatively mild autism symptoms. Other results were nonsignificant. Autism Res 2020, 13: 1902-1912. © 2020 International Society for Autism Research and Wiley Periodicals LLC LAY SUMMARY: Eighty-seven toddlers with autism spectrum disorders were randomly assigned to 15 hrs per week of discrete trial teaching (DTT), 25 hrs per week of DTT, 15 hrs per week of a naturalistic developmental behavioral intervention (NDBI), or 25 hrs per week of NDBI. Trained research staff implemented the treatments in homes or educational centers over 12 months. More hours of treatment per week benefited frequency and maturity of spontaneous communication growth rate only in children with relatively mild autism symptoms. Other results were nonsignificant.
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http://dx.doi.org/10.1002/aur.2416DOI Listing
November 2020

The role of early social motivation in explaining variability in functional language in toddlers with autism spectrum disorder.

Autism 2021 01 12;25(1):244-257. Epub 2020 Sep 12.

Vanderbilt University, USA.

Lay Abstract: About one-third of children with autism spectrum disorder never develop the language that they need in different day-to-day situations. Identifying potential factors that can predict later language development is crucial to understanding why some children with autism spectrum disorder successfully develop language while others do not. This study sought to investigate one of the understudied predictors of language development, social motivation, and to test theories for why this association may occur. Testing the theories requires that we measure children's ability to deliberately and directly communicate with others (i.e. intentional communication) and children's language understanding between the measures of social motivation and later expressive language. We tested 87 children with autism spectrum disorder, aged 14-31 months, at four times over 24 months. We found that children with relatively stronger social motivation had relatively better language use 2 years later. This positive link was partly due to a child's ability to produce intentional communication and to understand language. Although we did not measure parents' talking to their children, a theory that inspired this study suggests that children who use frequent intentional communication probably motivate others to talk with them frequently, which facilitates children's language understanding which leads to the development of expressive language. This theory, if confirmed to be true, can provide guidance for parents who want to help their children learn to talk. Parents could look for intentional communication from their children and respond by talking to their children. Effective intervention on both parent and child targets will likely enhance treatment efficacy. Future work is needed to test these ideas.
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http://dx.doi.org/10.1177/1362361320953260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011377PMC
January 2021

A Multisite Randomized Controlled Trial Comparing the Effects of Intervention Intensity and Intervention Style on Outcomes for Young Children With Autism.

J Am Acad Child Adolesc Psychiatry 2021 06 24;60(6):710-722. Epub 2020 Aug 24.

University of California, Los Angeles.

Objective: This randomized, multisite, intent-to-treat study tested the effects of 2 levels of treatment intensity (number of hours) and 2 treatment styles on the progress of young children with autism spectrum disorder (ASD). We predicted that initial severity of developmental delay or autism symptoms would moderate the effects of intensity and style on progress in 4 domains: autism symptom severity, expressive communication, receptive language, and nonverbal ability.

Method: A total of 87 children with ASD, mean age 23.4 months, were assigned to 1 of 2 intervention styles (naturalistic developmental/behavioral or discrete trial teaching), each delivered for either 15 or 25 hours per week of 1:1 intervention for 12 months by trained research staff. All caregivers received coaching twice monthly. Children were assessed at 4 timepoints. Examiners and coders were naive to treatment assignment.

Results: Neither style nor intensity had main effects on the 4 outcome variables. In terms of moderating the effects of initial severity of developmental delay and of autism symptom severity, neither moderated the effects of treatment style on progress in any of the 4 domains. In terms of treatment intensity, initial severity moderated effect of treatment intensity on only 1 domain, namely, change in autism symptom severity; in a secondary analysis, this effect was found in only 1 site.

Conclusion: Neither treatment style nor intensity had overall effects on child outcomes in the 4 domains examined. Initial severity did not predict better response to 1 intervention style than to another. We found very limited evidence that initial severity predicted better response to 25 vs 15 hours per week of intervention in the domains studied.

Clinical Trial Registration Information: Intervention Effects of Intensity and Delivery Style for Toddlers With Autism: https://clinicaltrials.gov/; NCT02272192.
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http://dx.doi.org/10.1016/j.jaac.2020.06.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057785PMC
June 2021

Characterizing Olfactory Function in Children with Autism Spectrum Disorder and Children with Sensory Processing Dysfunction.

Brain Sci 2020 Jun 10;10(6). Epub 2020 Jun 10.

Department of Radiology, University of Washington, Seattle, WA 98115, USA.

Abnormalities in olfactory function have been identified in a number of neurological and psychiatric disorders, including Parkinson's disease and schizophrenia. However, little is known about olfactory function in autism spectrum disorder (ASD). The present study aims to assess the olfactory profiles of children with ASD, compared to an age- and sex-matched comparison group of typically developing children and a second clinical control group consisting of non-ASD children with sensory processing dysfunction (SPD). Participants completed a battery of sensory and behavioral assessments including olfactory tasks (Sniffin' Sticks Threshold Test and self-reported valence ratings for two target odorants (phenylethyl alcohol and vanillin) and the University of Pennsylvania Smell Identification Test), and an autism evaluation (Autism Diagnostic Observation Schedule-2). Children with ASD showed intact odor detection with reduced odor identification ability. Poor odor identification was significantly correlated with autism symptom severity. Children with SPD demonstrated reduced odor detection and identification ability. These findings provide evidence for differential patterns of smell processing among ASD and non-ASD neurodevelopmental disorders. Future studies are needed to determine whether the association of impaired olfaction and increased autism symptoms is due to shared etiology.
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http://dx.doi.org/10.3390/brainsci10060362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348741PMC
June 2020

Predicting Expressive Language From Early Vocalizations in Young Children With Autism Spectrum Disorder: Which Vocal Measure Is Best?

J Speech Lang Hear Res 2020 05 13;63(5):1509-1520. Epub 2020 May 13.

Department of Psychiatry and Behavioral Sciences, University of California, Davis.

Purpose This study was designed to test the incremental validity of more expensive vocal development variables relative to less expensive variables for predicting later expressive language in children with autism spectrum disorder (ASD). We devote particular attention to the added value of coding the quality of vocalizations over the quantity of vocalizations because coding quality adds expense to the coding process. We are also interested in the added value of more costly human-coded vocal variables relative to those generated through automated analyses. Method Eighty-seven children with ASD aged 13-30 months at study initiation participated. For quantity of vocalizations, we derived one variable from human coding of brief communication samples and one from an automated process for daylong naturalistic audio samples. For quality of vocalizations, we derived four human-coded variables and one automated variable. A composite expressive language measure was derived at study entry, and 6 and 12 months later. The 12 months-centered intercept of a simple linear growth trajectory was used to quantify later expressive language. Results When statistically controlling for human-coded or automated quantity of vocalization variables, human-coded quality of vocalization variables exhibited incremental validity for predicting later expressive language skills. Human-coded vocal variables also predicted later expressive language skills when controlling for the analogous automated vocal variables. Conclusion In sum, these findings support devoting resources to human coding of the quality of vocalizations from communication samples to predict later expressive language skills in young children with ASD despite the greater costs of deriving these variables. Supplemental Material https://doi.org/10.23641/asha.12276458.
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http://dx.doi.org/10.1044/2020_JSLHR-19-00281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842121PMC
May 2020

Sleep Onset Problems and Subcortical Development in Infants Later Diagnosed With Autism Spectrum Disorder.

Am J Psychiatry 2020 06 7;177(6):518-525. Epub 2020 May 7.

Department of Speech and Hearing Sciences (MacDuffie, St. John, Estes), and Department of Radiology (Dager), University of Washington, Seattle; Department of Psychiatry (Shen, Styner, Kim), Biomedical Research Imaging Center (Styner), and Neurodevelopmental Research Center (Piven), University of North Carolina Chapel Hill; Department of Psychology, Temple University, Philadelphia (Paterson); Department of Child Psychiatry and Behavioral Sciences, Children's Hospital of Philadelphia (Pandey); Institute of Child Development (Elison), Department of Educational Psychology (Wolff), University of Minnesota, Minneapolis; Department of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson); Department of Child Psychiatry, Washington University School of Medicine in St. Louis (Botteron); and Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada (Zwaigenbaum).

Objective: Sleep patterns in children with autism spectrum disorder (ASD) appear to diverge from typical development in the second or third year of life. Little is known, however, about the occurrence of sleep problems in infants who later develop ASD and possible effects on early brain development. In a longitudinal neuroimaging study of infants at familial high or low risk for ASD, parent-reported sleep onset problems were examined in relation to subcortical brain volumes in the first 2 years of life.

Methods: A total of 432 infants were included across three study groups: infants at high risk who developed ASD (N=71), infants at high risk who did not develop ASD (N=234), and infants at low risk (N=127). Sleep onset problem scores (derived from an infant temperament measure) were evaluated in relation to longitudinal high-resolution T and T structural imaging data acquired at 6, 12, and 24 months of age.

Results: Sleep onset problems were more common at 6-12 months among infants who later developed ASD. Infant sleep onset problems were related to hippocampal volume trajectories from 6 to 24 months only for infants at high risk who developed ASD. Brain-sleep relationships were specific to the hippocampus; no significant relationships were found with volume trajectories of other subcortical structures examined (the amygdala, caudate, globus pallidus, putamen, and thalamus).

Conclusions: These findings provide initial evidence that sleep onset problems in the first year of life precede ASD diagnosis and are associated with altered neurodevelopmental trajectories in infants at high familial risk who go on to develop ASD. If replicated, these findings could provide new insights into a potential role of sleep difficulties in the development of ASD.
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http://dx.doi.org/10.1176/appi.ajp.2019.19060666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519575PMC
June 2020

Sex differences associated with corpus callosum development in human infants: A longitudinal multimodal imaging study.

Neuroimage 2020 07 7;215:116821. Epub 2020 Apr 7.

Department of Educational Psychology, University of Minnesota, Minneapolis, MN, USA. Electronic address:

The corpus callosum (CC) is the largest connective pathway in the human brain, linking cerebral hemispheres. There is longstanding debate in the scientific literature whether sex differences are evident in this structure, with many studies indicating the structure is larger in females. However, there are few data pertaining to this issue in infancy, during which time the most rapid developmental changes to the CC occur. In this study, we examined longitudinal brain imaging data collected from 104 infants at ages 6, 12, and 24 months. We identified sex differences in brain-size adjusted CC area and thickness characterized by a steeper rate of growth in males versus females from ages 6-24 months. In contrast to studies of older children and adults, CC size was larger for male compared to female infants. Based on diffusion tensor imaging data, we found that CC thickness is significantly associated with underlying microstructural organization. However, we observed no sex differences in the association between microstructure and thickness, suggesting that the role of factors such as axon density and/or myelination in determining CC size is generally equivalent between sexes. Finally, we found that CC length was negatively associated with nonverbal ability among females.
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http://dx.doi.org/10.1016/j.neuroimage.2020.116821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292750PMC
July 2020

Sleep Problems and Trajectories of Restricted and Repetitive Behaviors in Children with Neurodevelopmental Disabilities.

J Autism Dev Disord 2020 Nov;50(11):3844-3856

Department of Speech and Hearing Science, UW Autism Center, University of Washington, Box 957920, Seattle, WA, 98195, USA.

Sleep problems are prevalent in children with neurodevelopmental disabilities and are associated with the expression of restricted and repetitive behaviors (RRBs). Children (n = 57) with autism spectrum disorder (ASD, n = 38) or developmental delay (DD, n = 19) participated in multiple assessments of intellectual ability, ASD symptoms, and RRBs (3 timepoints for ASD, 2 for DD). Sleep problems assessed at age 4 via parent report were associated with trajectories of higher-order RRBs (sameness/ritualistic/compulsive behaviors) from age 2-6 in the ASD group, and from age 2-4 in the DD group, even after controlling for intellectual ability, social-affective symptoms, and anxiety. Trajectories of stereotyped/restricted behaviors were unrelated to sleep problems. Sleep problems were associated with trajectories of higher-order (but not lower-order) RRBs in a transdiagnostic sample.
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http://dx.doi.org/10.1007/s10803-020-04438-yDOI Listing
November 2020

Quantitative trait variation in ASD probands and toddler sibling outcomes at 24 months.

J Neurodev Disord 2020 02 5;12(1). Epub 2020 Feb 5.

Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill, Campus Box 3376, Chapel Hill, NC, 27599, USA.

Background: Younger siblings of children with autism spectrum disorder (ASD) are at increased likelihood of receiving an ASD diagnosis and exhibiting other developmental concerns. It is unknown how quantitative variation in ASD traits and broader developmental domains in older siblings with ASD (probands) may inform outcomes in their younger siblings.

Methods: Participants included 385 pairs of toddler siblings and probands from the Infant Brain Imaging Study. ASD probands (mean age 5.5 years, range 1.7 to 15.5 years) were phenotyped using the Autism Diagnostic Interview-Revised (ADI-R), the Social Communication Questionnaire (SCQ), and the Vineland Adaptive Behavior Scales, Second Edition (VABS-II). Siblings were assessed using the ADI-R, VABS-II, Mullen Scales of Early Learning (MSEL), and Autism Diagnostic Observation Schedule (ADOS) and received a clinical best estimate diagnosis at 24 months using DSM-IV-TR criteria (n = 89 concordant for ASD; n = 296 discordant). We addressed two aims: (1) to determine whether proband characteristics are predictive of recurrence in siblings and (2) to assess associations between proband traits and sibling dimensional outcomes at 24 months.

Results: Regarding recurrence risk, proband SCQ scores were found to significantly predict sibling 24-month diagnostic outcome (OR for a 1-point increase in SCQ = 1.06; 95% CI = 1.01, 1.12). Regarding quantitative trait associations, we found no significant correlations in ASD traits among proband-sibling pairs. However, quantitative variation in proband adaptive behavior, communication, and expressive and receptive language was significantly associated with sibling outcomes in the same domains; proband scores explained 9-18% of the variation in cognition and behavior in siblings with ASD. Receptive language was particularly strongly associated in concordant pairs (ICC = 0.50, p < 0.001).

Conclusions: Proband ASD symptomology, indexed by the SCQ, is a predictor of familial ASD recurrence risk. While quantitative variation in social communication and restricted and repetitive behavior were not associated among sibling pairs, standardized ratings of proband language and communication explained significant variation in the same domains in the sibling at 24 months, especially among toddlers with an ASD diagnosis. These data suggest that proband characteristics can alert clinicians to areas of developmental concern for young children with familial risk for ASD.
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http://dx.doi.org/10.1186/s11689-020-9308-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003330PMC
February 2020

"If He Has it, We Know What to Do": Parent Perspectives on Familial Risk for Autism Spectrum Disorder.

J Pediatr Psychol 2020 03;45(2):121-130

Research Triangle Institute, Center for Newborn Screening, Ethics, and Disability Studies.

Objective: Predictive testing for familial disorders can guide healthcare and reproductive decisions. Familial disorders with onset in childhood (e.g., autism spectrum disorder [ASD]) are promising targets for presymptomatic prediction; however, little is known about parent perceptions of risk to their children in the presymptomatic period. The current study examined risk perceptions in parents of infants at high familial risk for ASD enrolled in a longitudinal study of brain and behavior development.

Methods: Semistructured interviews were conducted with 37 parents of high-risk infants during the presymptomatic window (3-15 months) that precedes an ASD diagnosis. Infants were identified as high familial risk due to having an older sibling with ASD. Parent interview responses were coded and interpreted to distill emerging themes.

Results: The majority of parents were aware of the increased risk of ASD for their infants, and risk perceptions were influenced by comparisons to their older child with ASD. Parents reported a variety of negative emotions in response to perceived risk, including worry, fear, and sadness, and described impacts of perceived risk on their behavior: increased vigilance to emerging symptoms, altered reproductive and healthcare decisions, and seeking ongoing assessment through research.

Conclusions: Parents of children at high familial risk for childhood-onset disorders like ASD face a period of challenging uncertainty during early development. In anticipation of a future in which presymptomatic testing for ASD is made available, it is important to understand how parents react to and cope with the elevated-but still highly uncertain-risk conveyed by family history.
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http://dx.doi.org/10.1093/jpepsy/jsz076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029696PMC
March 2020

Validity of Vocal Communication and Vocal Complexity in Young Children with Autism Spectrum Disorder.

J Autism Dev Disord 2020 Jan;50(1):224-237

Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, USA.

To identify valid measures of vocal development in young children with autism spectrum disorder in the early stages of language learning, we evaluated the convergent validity, divergent validity, and sensitivity to change (across 12 months) of two measures of vocal communication and two measures of vocal complexity through conventional coding of communication samples. Participants included 87 children with autism spectrum disorder (M = 23.42 months at entry). All four vocal variables demonstrated consistent evidence of convergent validity, divergent validity, and sensitivity to change with large effect sizes for convergent validity and sensitivity to change. The results highlight the value of measuring vocal communication and vocal complexity in future studies.
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http://dx.doi.org/10.1007/s10803-019-04248-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949401PMC
January 2020

The effects of early autism intervention on parents and family adaptive functioning.

Pediatr Med 2019 Jun 12;2. Epub 2019 Jun 12.

Department of Speech and Hearing Sciences, University of Washington, Seattle, WA, USA.

This review describes the effects of intervention for young children with autism spectrum disorder (ASD) on parents. Like all children, children with ASD bring both negative and positive experiences for parents and families-from increased resource needs, to higher levels of parenting-related stress, to positive personal growth for family members. It is increasingly recognized that, although children with ASD are the primary targets of early ASD intervention, ASD intervention also impacts parents. From the time emerging developmental concerns begin to be identified, through the process of obtaining a diagnosis and initiating services, parents play a central role in addressing the needs of young children with ASD, including implementing and supporting early intervention. Parents experience the impact of intervention directly, through interaction with providers within the health care and educational systems. Parents also experience indirect impacts of ASD intervention due to accelerated developmental progress of children who are benefitting from services and when children make slower progress than expected or have challenging behaviors. Parental stress and psychological well-being are legitimate targets of intervention and compelling research objectives, needing no additional justification. However, parents are also the major contributors to family adaptive functioning-the activities families employ to support positive outcomes for children with ASD (e.g., family-orchestrated child experiences, parent-child interaction, child health and safety functions; Guralnick, 1997). A parent's ability to carry out adaptive functions is, in part, related to their levels of stress and psychological well-being. Thus, there is a transactional process in which parents are both impacted by and have an impact on ASD interventions for their child. Evaluating the effect of ASD intervention on parents is needed to develop new strategies for helping parents and children with ASD reach their full potential. This review will provide an overview of research on the impact of early ASD intervention on parents. Evidence regarding the impact of three types of intervention (i.e., early intensive behavioral intervention, parent-implemented intervention, and programs directly targeting parent stress) on parent well-being and family adaptive functioning will be reviewed. Potential moderators of the impact of ASD intervention on parents and family adaptive functioning will be discussed. We conclude that research on the impact of ASD intervention on parents of young children with ASD is a promising avenue for improving the lives of children with ASD and their families.
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http://dx.doi.org/10.21037/pm.2019.05.05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776235PMC
June 2019
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