1. Arora AS, Arora A, Sivakumar K, McIntyre JR. Managing social-educational robotics for students with autism spectrum disorder through business model canvas and customer discovery. Front Robot AI. 2024; 11: 1328467.

Social-educational robotics, such as NAO humanoid robots with social, anthropomorphic, humanlike features, are tools for learning, education, and addressing developmental disorders (e.g., autism spectrum disorder or ASD) through social and collaborative robotic interactions and interventions. There are significant gaps at the intersection of social robotics and autism research dealing with how robotic technology helps ASD individuals with their social, emotional, and communication needs, and supports teachers who engage with ASD students. This research aims to (a) obtain new scientific knowledge on social-educational robotics by exploring the usage of social robots (especially humanoids) and robotic interventions with ASD students at high schools through an ASD student-teacher co-working with social robot-social robotic interactions triad framework; (b) utilize Business Model Canvas (BMC) methodology for robot design and curriculum development targeted at ASD students; and (c) connect interdisciplinary areas of consumer behavior research, social robotics, and human-robot interaction using customer discovery interviews for bridging the gap between academic research on social robotics on the one hand, and industry development and customers on the other. The customer discovery process in this research results in eight core research propositions delineating the contexts that enable a higher quality learning environment corresponding with ASD students’ learning requirements through the use of social robots and preparing them for future learning and workforce environments.

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2. Brown H, Swain D, Kim HW, Rogers S, Estes A, Kasari C, Lord C, Kim SH. Examining variability in Naturalistic Developmental Behavioral Intervention strategy use in caregivers of children with autism spectrum disorders. J Child Psychol Psychiatry. 2024.

BACKGROUND: Naturalistic Developmental Behavioral Interventions (NDBIs) for young children with autism spectrum disorder commonly involve caregiver-mediated approaches. However, to date, there is limited research on how caregivers’ skills change, and, in turn, impact child outcomes. METHODS: We evaluated the NDBI strategy use of 191 caregivers prior to participation in NDBIs (or control groups) across multiple randomized controlled trials, using the Measure of NDBI Strategy Implementation, Caregiver Change (MONSI-CC). Clustering analyses were used to examine caregiver variability in NDBI strategy use at intervention entry. Generalized Linear Mixed Models were used to examine changes in caregiver strategy use over the course of intervention and its impact on changes in children’s social communication. RESULTS: Using clustering analysis, we found that caregivers’ baseline skills fit four profiles: limited, emerging, variable, and consistent/high, with few demographic factors distinguishing these groups. Caregivers starting with limited or emerging skills improved in their strategy use with intervention. Caregivers starting with more skills (consistent/high or variable) maintained higher skills over intervention. Children of caregivers in these groups who received target NDBIs improved in their social communication skills. CONCLUSIONS: Results suggested that caregiver skills improve through participation in NDBIs and may directly contribute to their children’s outcomes, although more research on mediating factors is needed. Individualized approaches for caregivers and their children starting with differing skill profiles at intervention entry may be warranted.

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3. Cherchi C, Chiappini E, Amaddeo A, Chiarini Testa MB, Banfi P, Veneselli E, Cutrera R. Management of respiratory issues in patients with Rett syndrome: Italian experts’ consensus using a delphi approach. Pediatr Pulmonol. 2024.

BACKGROUND: Despite the publication of the 2020 guidelines on how to manage Rett Syndrome (RS), some fundamental topics are still open, in particular respiratory problems. OBJECTIVE: Identification and reinforcement of current recommendations concerning the management of respiratory issues in RS patients. MATERIALS AND METHODS: Using a Delphi approach, the leading group reviewed the literature and formulated 14 statements. A multidisciplinary panel of 29 experts were invited to score, for each statement, their agreement on a 1-5 scale. The cut-off level for consensus was 75%, obtained through multiple rounds. RESULTS: The panel agreed that in all RS types, respiratory issues should be faced at an early stage, regardless of epilepsy onset. It is recommended to perform periodically sleep studies in all Congenital Rett Syndrome, and in selected cases with other RS types. Noninvasive ventilation should be considered in all RS subjects with sleep respiratory disorders and in those with hypotonia associated with hypercapnia. Chest physiotherapy should be performed in all RS patients with difficult management of the accumulation of respiratory secretions, using airway clearance techniques and devices (PEP-mask, AMBU bag, or cough machine), more appropriate and tolerated by the patients. The panel recommended individualized programs for the management of scoliosis, and to consider performing gastrostomy in patients at increased risk of ab ingestis pneumonia. CONCLUSIONS: This consensus could support everyday clinical practice on respiratory issues in RS patients, complementary to existing recommendations by regulatory agencies and guidelines.

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4. Croom K, Rumschlag JA, Erickson MA, Binder D, Razak KA. Sex differences during development in cortical temporal processing and event related potentials in wild-type and fragile X syndrome model mice. J Neurodev Disord. 2024; 16(1): 24.

BACKGROUND: Autism spectrum disorder (ASD) is currently diagnosed in approximately 1 in 44 children in the United States, based on a wide array of symptoms, including sensory dysfunction and abnormal language development. Boys are diagnosed ~ 3.8 times more frequently than girls. Auditory temporal processing is crucial for speech recognition and language development. Abnormal development of temporal processing may account for ASD language impairments. Sex differences in the development of temporal processing may underlie the differences in language outcomes in male and female children with ASD. To understand mechanisms of potential sex differences in temporal processing requires a preclinical model. However, there are no studies that have addressed sex differences in temporal processing across development in any animal model of ASD. METHODS: To fill this major gap, we compared the development of auditory temporal processing in male and female wildtype (WT) and Fmr1 knock-out (KO) mice, a model of Fragile X Syndrome (FXS), a leading genetic cause of ASD-associated behaviors. Using epidural screw electrodes, we recorded auditory event related potentials (ERP) and auditory temporal processing with a gap-in-noise auditory steady state response (ASSR) paradigm at young (postnatal (p)21 and p30) and adult (p60) ages from both auditory and frontal cortices of awake, freely moving mice. RESULTS: The results show that ERP amplitudes were enhanced in both sexes of Fmr1 KO mice across development compared to WT counterparts, with greater enhancement in adult female than adult male KO mice. Gap-ASSR deficits were seen in the frontal, but not auditory, cortex in early development (p21) in female KO mice. Unlike male KO mice, female KO mice show WT-like temporal processing at p30. There were no temporal processing deficits in the adult mice of both sexes. CONCLUSIONS: These results show a sex difference in the developmental trajectories of temporal processing and hypersensitive responses in Fmr1 KO mice. Male KO mice show slower maturation of temporal processing than females. Female KO mice show stronger hypersensitive responses than males later in development. The differences in maturation rates of temporal processing and hypersensitive responses during various critical periods of development may lead to sex differences in language function, arousal and anxiety in FXS.

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5. Dell’Osso L, Amatori G, Bonelli C, Nardi B, Massimetti E, Cremone IM, Carpita B. Panic-agoraphobic symptoms in adults with ASD: the role of ruminative thinking and inflexibility. CNS Spectr. 2024: 1-24.

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6. Dijkstra-de Neijs L, Boeke DB, van Berckelaer-Onnes IA, Swaab H, Ester WA. Parental Stress and Quality of Life in Parents of Young Children with Autism. Child Psychiatry Hum Dev. 2024.

Parents of children with ASD are at risk for chronic stress due to challenging parenting. It is unknown whether stress is already present in early parenthood, similar for mothers and fathers and if this impacts quality of life (QoL). Parental stress and QoL were assessed in 56 mothers and 51 fathers of young children (aged 3 to 7) with autism. Associations between parental stress (OBVL) and QoL (WHOQoL-BREF) were examined. Parents of young children with ASD appear to have high parental stress from conflicting feelings towards their child and from difficulties with parenting. Mothers have higher stress from feeling confined in their motherly role than fathers compared to the OBVL norm population. Both mothers and fathers have a low QoL. Increased maternal conflicting feelings towards the child associated with lower psychological QoL, while high maternal feelings of role confinement associated with low physical QoL. Increased paternal conflicting feelings towards their child related to lower physical and social QoL, while fathers with more parenting difficulties reported less satisfaction with their psychological and environmental wellbeing. Thus, already at young age, parenting children with ASD is a major challenge for both mothers and fathers.

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7. Egilmez CB, Pazarlar BA, Erdogan MA, Uyanikgil Y, Erbas O. Choline chloride shows gender-dependent positive effects on social deficits, learning/memory impairments, neuronal loss and neuroinflammation in the lipopolysaccharide-induced rat model of autism. Int J Dev Neurosci. 2024.

The neuroprotective effects of choline chloride, an essential nutrient, a precursor for the acetylcholine and synthesis of membrane phospholipids, have been associated with neurological and neurodegenerative diseases. Its contribution to autism spectrum disorder, a neurodevelopmental disorder, remains unknown. Thus, we aimed to evaluate the effects of choline chloride on social behaviours, and histopathological and biochemical changes in a rat autism model. The autism model was induced by administration of 100 μg/kg lipopolysaccharide (LPS) on the 10th day of gestation. Choline chloride treatment (100 mg/kg/day) was commenced on PN5 and maintained until PN50. Social deficits were assessed by three-chamber sociability, open field, and passive avoidance learning tests. Tumour necrosis factor alpha (TNF-α), interleukin-2 (IL) and IL-17, nerve growth factor (NGF), and glutamate decarboxylase 67 (GAD67) levels were measured to assess neuroinflammatory responses. In addition, the number of hippocampal and cerebellar neurons and glial fibrillary acidic protein (GFAP) expression were evaluated. Social novelty and passive avoidance learning tests revealed significant differences in choline chloride-treated male rats compared with saline-treated groups. TNF-α, IL-2, and IL-17 were significantly decreased after choline chloride treatment in both males and females. NGF and GAD67 levels were unchanged in females, while there were significant differences in males. Histologically, significant changes in terms of gliosis were detected in hippocampal CA1 and CA3 regions and cerebellum in choline chloride-treated groups. The presence of ameliorative effects of choline chloride treatment on social behaviour and neuroinflammation through neuroinflammatory, neurotrophic, and neurotransmission pathways in a sex-dependent rat model of LPS-induced autism was demonstrated.

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8. Holc S, Yailian A, Pernon E, Baghdadli A. Barriers and facilitators to achieving employment in mainstream settings in adults with autism spectrum disorder without intellectual developmental disorders: A scoping review. Encephale. 2024.

Autistic people without Intellectual Developmental Disorders (IDD) have a significantly lower employment rate compared to the general population even though employment favors social integration and quality of life. AIMS: To examine the barriers and facilitators to employability in mainstream settings for autistic adults without intellectual disability. METHODS: Following the scoping review guidelines, we searched the Cochrane, PubMed and PsycINFO databases for references published between 01/01/2000 to 01/08/2023. RESULTS: A review of the 44 identified articles suggests the existence of multiple individual and environmental factors influencing job access and retention. CONCLUSIONS: This is the first review to assess the facilitators and barriers to employment support for autistic people without intellectual disability. The results underline the need for studying strategies to promote access to employment and job retention for autistic people. Future research should explore the mediating and moderating factors leading to the improvement of employability of autistic people WIDD.

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9. Ip BYT, Lee SL, Li SX. Telehealth-delivered parent-based sleep-focused intervention for insomnia in preschool children with autism spectrum disorder: A randomized controlled study. Autism. 2024: 13623613241246502.

Sleep problems are common in children with autism spectrum disorder. Although the effects of parent-based sleep intervention were shown to be promising, previous research was limited to the face-to-face service model, which might limit accessibility. This study examined a sleep-focused parent training group delivered via telehealth for treating insomnia in preschool children with autism spectrum disorder, which allowed parents to join the intervention remotely. Results showed that children in the intervention group had greater improvements in sleep and insomnia symptoms after treatment, as compared to those who only received care as usual. This sleep-focused treatment also led to improved daytime behaviors, especially externalizing problems such as hyperactivity and conduct problems, in children with autism spectrum disorder. Parents who had attended the training also reported reduced parental stress level after treatment. The findings supported the feasibility and promising effects of a brief parent-based sleep intervention delivered via telehealth for preschooler with autism spectrum disorder.

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10. Jagadeeswaran I, Oh J, Sinnett SE. Preclinical milestones in MECP2 gene transfer for treating Rett syndrome. Dev Neurosci. 2024.

BACKGROUND: Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the transcriptional regulator methyl-CpG-binding protein 2 (MeCP2). After gene transfer in mice, exogenous MeCP2 expression must be regulated to avoid dose-dependent toxicity. SUMMARY: The preclinical gene therapy literature for treating Rett syndrome (RTT) illustrates a duly diligent progression that begins with proof-of-concept studies and advances toward the development of safer, regulated MECP2 viral genome designs. This design progression was partly achieved through international collaborative studies. In 2023, clinicians administered investigational gene therapies for RTT to patients a decade after the first preclinical gene therapy publications for RTT (clinical trial numbers NCT05606614 and NCT05898620). As clinicians take on a more prominent role in MECP2 gene therapy research, preclinical researchers may continue to test more nuanced hypotheses regarding the safety, efficacy, and mechanism of MECP2 gene transfer. KEY MESSAGE: This review summarizes the history of preclinical MECP2 gene transfer for treating RTT and acknowledges major contributions among colleagues in the field. The first clinical injections are a shared milestone.

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11. Lewis GF, daSilva EB, Aghajani M, Date S, Jaime M. Level of autistic traits in neurotypical adults predicts kinematic idiosyncrasies in their biological movements. Front Integr Neurosci. 2024; 18: 1364249.

INTRODUCTION: Over the last decade of research, a notable connection between autism spectrum disorder (ASD) and unique motor system characteristics has been identified, which may influence social communication through distinct movement patterns. In this study, we investigated the potential for features of the broader autism phenotype to account for kinematic idiosyncrasies in social movements expressed by neurotypical individuals. METHODS: Fifty-eight participants provided recordings of point-light displays expressing three basic emotions and completed the Autism Spectrum Quotient (AQ). We extracted kinematic metrics from the biological movements using computer vision and applied linear mixed-effects modeling to analyze the relationship between these kinematic metrics and AQ scores. RESULTS: Our results revealed that individual differences in the total AQ scores, and the sub-scale scores, significantly predicted variations in kinematic metrics representing order, volume, and magnitude. DISCUSSION: The results of this study suggest that autistic traits may intricately influence the movement expressions at the microlevel, highlighting the need for a more nuanced understanding of the potential endophenotypic characteristics associated with social movements in neurotypical individuals.

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12. Paynter J, Heng V, Tucker M, Malone S. A Longitudinal Analysis of Mothers’ Parenting Stress and Internalizing and Externalizing Behavior of Young Children on the Autism Spectrum. J Autism Dev Disord. 2024.

We investigated longitudinal relations between internalizing, externalizing, and total behaviors that challenge in young children on the autism spectrum and mothers’ parenting stress. Participants included 93 mothers of children on the autism spectrum aged 27.89-65.84 months, who completed questionnaires on maternal parenting stress, and children’s internalizing (anxiety), externalizing (disruptive), and total behaviors that challenge. Data were collected on early intervention program intake and approximately one year later. Cross-sectional findings indicated small to medium effect size associations between internalizing and externalizing behavior and parenting stress. However, cross-lagged structural equation models found that neither internalizing nor externalizing behavior predicted later parenting stress, nor the reverse. Significant stability effects were found for measures of child internalizing (anxiety), externalizing (disruptive), and total behaviors, and parenting stress. Relations between behaviors that challenge and parenting stress over time were non-significant in our models that controlled for stability of behaviors and parenting stress over time. Implications for research and clinical practice, in understanding and targeting the persistence of behaviors that challenge and parenting stress, are discussed.

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13. Peterson M, Prigge MBD, Floris DL, Bigler ED, Zielinski BA, King JB, Lange N, Alexander AL, Lainhart JE, Nielsen JA. Reduced lateralization of multiple functional brain networks in autistic males. J Neurodev Disord. 2024; 16(1): 23.

BACKGROUND: Autism spectrum disorder has been linked to a variety of organizational and developmental deviations in the brain. One such organizational difference involves hemispheric lateralization, which may be localized to language-relevant regions of the brain or distributed more broadly. METHODS: In the present study, we estimated brain hemispheric lateralization in autism based on each participant’s unique functional neuroanatomy rather than relying on group-averaged data. Additionally, we explored potential relationships between the lateralization of the language network and behavioral phenotypes including verbal ability, language delay, and autism symptom severity. We hypothesized that differences in hemispheric asymmetries in autism would be limited to the language network, with the alternative hypothesis of pervasive differences in lateralization. We tested this and other hypotheses by employing a cross-sectional dataset of 118 individuals (48 autistic, 70 neurotypical). Using resting-state fMRI, we generated individual network parcellations and estimated network asymmetries using a surface area-based approach. A series of multiple regressions were then used to compare network asymmetries for eight significantly lateralized networks between groups. RESULTS: We found significant group differences in lateralization for the left-lateralized Language (d = -0.89), right-lateralized Salience/Ventral Attention-A (d = 0.55), and right-lateralized Control-B (d = 0.51) networks, with the direction of these group differences indicating less asymmetry in autistic males. These differences were robust across different datasets from the same participants. Furthermore, we found that language delay stratified language lateralization, with the greatest group differences in language lateralization occurring between autistic males with language delay and neurotypical individuals. CONCLUSIONS: These findings evidence a complex pattern of functional lateralization differences in autism, extending beyond the Language network to the Salience/Ventral Attention-A and Control-B networks, yet not encompassing all networks, indicating a selective divergence rather than a pervasive one. Moreover, we observed an association between Language network lateralization and language delay in autistic males.

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14. Smith JV, McQuaid GA, Wallace GL, Neuhaus E, Lopez A, Ratto AB, Jack A, Khuu A, Webb SJ, Verbalis A, Pelphrey KA, Kenworthy L. Time is of the essence: Age at autism diagnosis, sex assigned at birth, and psychopathology. Autism. 2024: 13623613241249878.

Previous research has shown that girls/women are diagnosed later than boys/men with autism. Individuals who are diagnosed later in life, especially girls/women, have greater anxious and depressive symptoms. Previous research has been limited due to narrow inclusionary criteria for enrollment in studies. The present study uses two samples-one clinic-based, large « real-world » sample and another research-based sample with strict criteria for autism diagnosis-to understand the relationships between diagnostic age, sex assigned at birth, and symptoms of anxiety/depression. In both samples, those who were diagnosed later had greater anxious/depressive symptoms, and anxiety was not predicted by sex. In the clinic-based but not research-based sample, those assigned female at birth were diagnosed later than those assigned male at birth. In the clinic-based sample only, individuals assigned female at birth and who were later diagnosed experienced greater symptoms of anxiety/depression compared to those assigned male who benefited from earlier diagnostic timing. Within the research-based sample, those assigned female at birth had greater depressive symptoms than those assigned male. These findings highlight the importance of timely identification of autism, especially for girls/women who are often diagnosed later. Community-based samples are needed to better understand real-world sex-based and diagnostic age-based disparities in mental health.

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15. Su YE, Jiang Y. Challenges with computing scalar and ad-hoc implicatures in Mandarin-speaking 4-8-year-old autistic children. J Commun Disord. 2024; 110: 106427.

INTRODUCTION: Mixed findings have been reported about the computation of scalar or/and ad-hoc implicatures in primarily school-age autistic verbal children and adolescents: while some studies reported their struggles with both implicatures, others observed their strengths in computing scalar implicatures. This study extends the previous investigation by testing the derivation of scalar (including both number and quantifier) and ad-hoc implicatures of a younger group of Mandarin-speaking autistic 4-8-year-olds; moreover, we assess the biological, linguistic, and cognitive factors affecting children’s implicature acquisition. METHODS: The participants included 22 4-8-year-old autistic verbal children (mean age = 67.64 months) and 19 typically developing (TD) children who did not significantly differ in age, receptive vocabulary, and non-verbal IQ. Both groups completed a computer-based Truth Value Judgment task, assessing their knowledge of scalar (involving the number ‘three’ and the quantifier ‘some’) and ad-hoc implicatures. We also examined whether their implicature computation was linked to age, receptive vocabulary, non-verbal IQ, and Theory of Mind (ToM). RESULTS: Compared with the TD controls, autistic children derived significantly fewer scalar and ad-hoc implicatures. Specifically, TD children successfully computed number and ad-hoc implicatures, contrasting to the bimodal distribution of their pragmatic vs. logical responses to quantifier implicatures. Though autistic children performed better with number implicatures slightly above the chance level, they had difficulties in computing quantifier and ad-hoc implicatures. Further, autistic children’s knowledge of the number and ad-hoc implicatures was linked to their ToM skills. CONCLUSIONS: These findings underscore the overall delayed implicature knowledge of young autistic children, and their low sensitivity to the implicatures is related to the core ToM deficits. Furthermore, our data confirm the coherent pattern of the earlier acquisition of number over quantifier implicatures and illuminate the distinct mechanisms underlying the computation of scalar vs. ad-hoc implicatures.

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16. Wieckowski AT, Perez Liz G, de Marchena A, Fein DA, Barton ML, Vivanti G, Robins DL. Development of a school-age extension of the Modified Checklist for Autism in Toddlers through expert consensus and stakeholder input. Autism. 2024: 13623613241252312.

The American Academy of Pediatrics recommends universal screening to identify children at higher likelihood for autism at 18- and 24-month well-child visits. There are many children, however, that are missed during this toddler age who do not get diagnosed until much later in development, delaying access to autism-specific interventions. Currently, brief measures for universal autism screening for school-age children, however, are lacking. In this project, we adapted a commonly used autism screener for toddlers, the Modified Checklist for Autism in Toddlers, Revised, with Follow-Up (M-CHAT-R/F), to be used for school-age children. This measure, called the M-CHAT-School (M-CHAT-S), is a parent- and teacher-report questionnaire to be used to screen for autism in school-age children aged 4 to 8 years of age. M-CHAT-S was developed through feedback from autism experts, as well as interviews with parents and teachers to provide input on the items. Two versions of M-CHAT-S were developed, one for verbally fluent and one for minimally verbal school-age children. M-CHAT-S is a brief measure, with updated items to reflect changes in the way experts think and talk about autism, making it a useful measure to use for autism screening in elementary aged children. The next steps include further testing to ensure that M-CHAT-S performs well in identifying children with increased likelihood of autism, after which it will be made available to parents, educators, and other professionals.

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