Electrophysiological Measures of Listening-in-Noise With and Without Remote Microphone System Use in Autistic and Non-Autistic Youth.

OBJECTIVES: This study examined the neural mechanisms by which remote microphone (RM) systems might lead to improved behavioral performance on listening-in-noise tasks in autistic and non-autistic youth. DESIGN: Cortical auditory evoked potentials (CAEPs) were recorded in autistic (n = 25) and non-autistic (n = 22) youth who were matched at the group level on chronological age ( M = 14.21 ± 3.39 years) and biological sex. Potentials were recorded during an active syllable identification task completed in quiet and in multi-talker babble noise with and without the use of an RM system. The effects of noise and RM system use on speech-sound-evoked P1-N1-P2 responses and the associations between the cortical responses and behavioral performance on syllable identification were examined. RESULTS: No group differences were observed for behavioral or CAEP measures of speech processing in quiet or in noise. In the combined sample, syllable identification in noise was less accurate and slower than in the quiet condition. The addition of the RM system to the noise condition restored accuracy, but not the response speed, to the levels observed in quiet. The CAEP analyses noted amplitude reductions and latency delays in the noise compared with the quiet condition. The RM system use increased the N1 amplitude as well as reduced and delayed the P2 response relative to the quiet and noise conditions. Exploratory brain-behavior correlations revealed that larger N1 amplitudes in the RM condition were associated with greater behavioral accuracy of syllable identification. Reduced N1 amplitude and accelerated P2 response were associated with shorter syllable identification response times when listening with the RM system. CONCLUSIONS: Findings suggest that although listening-in-noise with an RM system might remain effortful, the improved signal to noise ratio facilitates attention to the sensory features of the stimuli and increases speech sound identification accuracy.

Remote Microphone Systems for Autistic and Nonautistic Youth: Effects on Audiovisual Task Engagement.

OBJECTIVES: A recent study has provided empirical support for the use of remote microphone (RM) systems to improve listening-in-noise performance of autistic youth. It has been proposed that RM system effects might be achieved by boosting engagement in this population. The present study used behavioral coding to test this hypothesis in autistic and nonautistic youth listening in an ecologically valid, noisy environment. DESIGN: We drew on extant data from a recent experimental study in which 56 youth (32 autistic, 24 nonautistic) matched at the group level on age and biological sex completed listening-in-noise tasks wherein they reported their perception of audiovisual syllables, words, sentences, and passages with and without an RM system; conditions were counter-balanced across participants. As previously reported, perceptual accuracy varied with stimulus complexity and overall improved with the RM system, with improvements not significantly different between groups. Video recordings of participants completing listening-in-noise tasks in both conditions were coded via a 5-second, partial-interval coding system by naive coders for (a) engagement in the task (indexed via proportion of intervals in which participants displayed on-task behaviors) and (b) verbal, stimulus-specific protesting in the task (indexed via proportion of intervals in which participants displayed verbal, stimulus-specific protesting behaviors). Examples of on-task behaviors included attending to the screen and completing task activities. Examples of protesting behaviors included complaining about stimuli volume or the inability to hear. Chronological age, autism features, language ability, audiovisual speech integration as measured by psychophysical tasks, tactile responsiveness, and nonverbal intelligence quotient were evaluated as putative predictors and/or moderators of effects on behaviors of interest. RESULTS: In general, participants were highly engaged in the task, and there were few protests, reflecting more than 90% and fewer than 0.5% of coded intervals, respectively. We did not detect any statistically significant effects of group or RM system use on task engagement. Nonautistic youth were engaged in the listening-in-noise task for an average of 97.45% of intervals, whereas autistic youth were engaged in the listening-in-noise task for an average of 94.25% of intervals. In contrast, verbal, stimulus-specific protesting in the listening-in-noise task was significantly reduced, on average, in the RM (0.04% of intervals) versus the No RM (0.2% of intervals) conditions. There were no effects related to group for this behaviorally coded outcome. In addition, select participant characteristics predicted engagement within conditions across participants. Greater language ability and nonverbal intelligence quotient predicted increased engagement when not using an RM system. Increased features of autism and wider temporal binding windows for audiovisual speech predicted reduced engagement while using an RM system, and greater audiovisual integration predicted increased engagement while using an RM system. CONCLUSIONS: The results of this study suggest that RM system use reduces verbal, stimulus-specific protesting, which likely reflects difficulty engaging when listening in noise. The present study extends our previous study to provide additional empirical support for RM system use in autistic and nonautistic youth.

Remote Microphone Systems Can Improve Listening-in-Noise Accuracy and Listening Effort for Youth With Autism.

OBJECTIVES: This study examined whether remote microphone (RM) systems improved listening-in-noise performance in youth with autism. We explored effects of RM system use on both listening-in-noise accuracy and listening effort in a well-characterized sample of participants with autism. We hypothesized that listening-in-noise accuracy would be enhanced and listening effort reduced, on average, when participants used the RM system. Furthermore, we predicted that effects of RM system use on listening-in-noise accuracy and listening effort would vary according to participant characteristics. Specifically, we hypothesized that participants who were chronologically older, had greater nonverbal cognitive and language ability, displayed fewer features of autism, and presented with more typical sensory and multisensory profiles might exhibit greater benefits of RM system use than participants who were younger, had less nonverbal cognitive or language ability, displayed more features of autism, and presented with greater sensory and multisensory disruptions. DESIGN: We implemented a within-subjects design to investigate our hypotheses, wherein 32 youth with autism completed listening-in-noise testing with and without an RM system. Listening-in-noise accuracy and listening effort were evaluated simultaneously using a dual-task paradigm for stimuli varying in complexity (i.e., syllable-, word-, sentence-, and passage-level). In addition, several putative moderators of RM system effects (i.e., sensory and multisensory function, language, nonverbal cognition, and broader features of autism) on outcomes of interest were evaluated. RESULTS: Overall, RM system use resulted in higher listening-in-noise accuracy in youth with autism compared with no RM system use. The observed benefits were all large in magnitude, although the benefits on average were greater for more complex stimuli (e.g., key words embedded in sentences) and relatively smaller for less complex stimuli (e.g., syllables). Notably, none of the putative moderators significantly influenced the effects of the RM system on listening-in-noise accuracy, indicating that RM system benefits did not vary according to any of the participant characteristics assessed. On average, RM system use did not have an effect on listening effort across all youth with autism compared with no RM system use but instead yielded effects that varied according to participant profile. Specifically, moderated effects indicated that RM system use was associated with increased listening effort for youth who had (a) average to below-average nonverbal cognitive ability, (b) below-average language ability, and (c) reduced audiovisual integration. RM system use was also associated with decreased listening effort for youth with very high nonverbal cognitive ability. CONCLUSIONS: This study extends prior work by showing that RM systems have the potential to boost listening-in-noise accuracy for youth with autism. However, this boost in accuracy was coupled with increased listening effort, as indexed by longer reaction times while using an RM system, for some youth with autism, perhaps suggesting greater engagement in the listening-in-noise tasks when using the RM system for youth who had lower cognitive abilities, were less linguistically able, and/or have difficulty integrating seen and heard speech. These findings have important implications for clinical practice, suggesting RM system use in classrooms could potentially improve listening-in-noise performance for some youth with autism.

Cortical Morphology in Autism: Findings from a Cortical Shape-Adaptive Approach to Local Gyrification Indexing.

It has been challenging to elucidate the differences in brain structure that underlie behavioral features of autism. Prior studies have begun to identify patterns of changes in autism across multiple structural indices, including cortical thickness, local gyrification, and sulcal depth. However, common approaches to local gyrification indexing used in prior studies have been limited by low spatial resolution relative to functional brain topography. In this study, we analyze the aforementioned structural indices, utilizing a new method of local gyrification indexing that quantifies this index adaptively in relation to specific sulci/gyri, improving interpretation with respect to functional organization. Our sample included n = 115 autistic and n = 254 neurotypical participants aged 5-54, and we investigated structural patterns by group, age, and autism-related behaviors. Differing structural patterns by group emerged in many regions, with age moderating group differences particularly in frontal and limbic regions. There were also several regions, particularly in sensory areas, in which one or more of the structural indices of interest either positively or negatively covaried with autism-related behaviors. Given the advantages of this approach, future studies may benefit from its application in hypothesis-driven examinations of specific brain regions and/or longitudinal studies to assess brain development in autism.

Evidence-b(i)ased practice: Selective and inadequate reporting in early childhood autism intervention research.

LAY ABSTRACT: When researchers fail to report their findings or only report some of their findings, it can make it difficult for clinicians to provide effective intervention recommendations. However, no one has examined whether this is a problem in studies of early childhood autism interventions. We studied how researchers that study early childhood autism interventions report their findings. We found that most researchers did not register their studies when they were supposed to (before the start of the study), and that many researchers did not provide all of the needed information in the registration. We also found that researchers frequently did not publish their findings when their studies were complete. When we looked at published reports, we found that many of the studies did not report enough information, and that many studies were reported differently from their registrations, suggesting that researchers were selectively reporting positive outcomes and ignoring or misrepresenting less positive outcomes. Because we found so much evidence that researchers are failing to report their findings quickly and correctly, we suggested some practical changes to make it better.

Determining Associations Between Intervention Amount and Outcomes for Young Autistic Children: A Meta-Analysis.

Importance: Health professionals routinely recommend intensive interventions (ie, 20-40 hours per week) for autistic children. However, primary research backing this recommendation is sparse and plagued by methodological flaws. Objective: To examine whether different metrics of intervention amount are associated with intervention effects on any developmental domain for young autistic children. Data Sources: A large corpus of studies taken from a recent meta-analysis (with a search date of November 2021) of early interventions for autistic children. Study Selection: Studies were eligible if they reported a quasi-experimental or randomized clinical trial testing the effects of a nonpharmacological intervention on any outcome in participant samples comprising more than 50% autistic children 8 years or younger. Data Extraction and Synthesis: Data were independently extracted by multiple coders. Meta-regression models were constructed to determine whether each index of intervention amount was associated with effect sizes for each intervention type, while controlling for outcome domain, outcome proximity, age of participants, study design, and risk of detection bias. Data were analyzed from June 2023 to February 2024. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Main Outcomes and Measures: The primary predictor of interest was intervention amount, quantified using 3 different metrics (daily intensity, duration, and cumulative intensity). The primary outcomes of interest were gains in any developmental domain, quantified by Hedges g effect sizes. Results: A total of 144 studies including 9038 children (mean [SD] age, 49.3 [17.2] months; mean [SD] percent males, 82.6% [12.7%]) were included in this analysis. None of the meta-regression models evidenced a significant, positive association between any index of intervention amount and intervention effect size when considered within intervention type. Conclusions and Relevance: Findings of this meta-analysis do not support the assertion that intervention effects increase with increasing amounts of intervention. Health professionals recommending interventions should be advised that there is little robust evidence supporting the provision of intensive intervention.

Diversity of Research Participant Gender, Race, and Ethnicity in Communication Sciences and Disorders: A Systematic Review and Quantitative Synthesis of American Speech-Language-Hearing Association Publications in 2020.

Purpose: One manifestation of systemic inequities in communication sciences and disorders (CSD) is the chronic underreporting and underrepresentation of sex, gender, race, and ethnicity in research. The present study characterized recent demographic reporting practices and representation of participants across CSD research. Methods: We systematically reviewed and extracted key reporting and participant data from empirical studies conducted in the United States (US) with human participants published in the year 2020 in journals by the American Speech-Language-Hearing Association (ASHA; k = 407 articles comprising a total n = 80,058 research participants, search completed November 2021). Sex, gender, race, and ethnicity were operationalized per National Institutes of Health guidelines (National Institutes of Health, 2015a, 2015b). Results: Sex or gender was reported in 85.5% of included studies; race was reported in 33.7%; and ethnicity was reported in 13.8%. Sex and gender were clearly differentiated in 3.4% of relevant studies. Where reported, median proportions for race and ethnicity were significantly different from the US population, with underrepresentation noted for all non-White racial groups and Hispanic participants. Moreover, 64.7% of studies that reported sex or gender and 67.2% of studies that reported race or ethnicity did not consider these respective variables in analyses or discussion. Conclusion: At present, research published in ASHA journals frequently fails to report key demographic data summarizing the characteristics of participants. Moreover, apparent gaps in representation of minoritized racial and ethnic groups threaten the external validity of CSD research and broader health care equity endeavors in the US. Although our study is limited to a single year and publisher, our results point to several steps for readers that may bring greater accountability, consistency, and diversity to the discipline.

Audiovisual multisensory integration in individuals with reading and language impairments: A systematic review and meta-analysis.

Differences in sensory function have been documented for a number of neurodevelopmental conditions, including reading and language impairments. Prior studies have measured audiovisual multisensory integration (i.e., the ability to combine inputs from the auditory and visual modalities) in these populations. The present study sought to systematically review and quantitatively synthesize the extant literature on audiovisual multisensory integration in individuals with reading and language impairments. A comprehensive search strategy yielded 56 reports, of which 38 were used to extract 109 group difference and 68 correlational effect sizes. There was an overall difference between individuals with reading and language impairments and comparisons on audiovisual integration. There was a nonsignificant trend towards moderation according to sample type (i.e., reading versus language) and publication/small study bias for this model. Overall, there was a small but non-significant correlation between metrics of audiovisual integration and reading or language ability; this model was not moderated by sample or study characteristics, nor was there evidence of publication/small study bias. Limitations and future directions for primary and meta-analytic research are discussed.

A Comparison of Listening Skills of Autistic and Non-Autistic Youth While Using and Not Using Remote Microphone Systems.

OBJECTIVES: The purposes of this study were to compare (a) listening-in-noise (accuracy and effort) and (b) remote microphone (RM) system benefits between autistic and non-autistic youth. DESIGN: Groups of autistic and non-autistic youth that were matched on chronological age and biological sex completed listening-in-noise testing when wearing and not wearing an RM system. Listening-in-noise accuracy and listening effort were evaluated simultaneously using a dual-task paradigm for stimuli varying in type (syllables, words, sentences, and passages). Several putative moderators of RM system effects on outcomes of interest were also evaluated. RESULTS: Autistic youth outperformed non-autistic youth in some conditions on listening-in-noise accuracy; listening effort between the two groups was not significantly different. RM system use resulted in listening-in-noise accuracy improvements that were nonsignificantly different across groups. Benefits of listening-in-noise accuracy were all large in magnitude. RM system use did not have an effect on listening effort for either group. None of the putative moderators yielded effects of the RM system on listening-in-noise accuracy or effort for non-autistic youth that were significant and interpretable, indicating that RM system benefits did not vary according to any of the participant characteristics assessed. CONCLUSIONS: Contrary to expectations, autistic youth did not demonstrate listening-in-noise deficits compared to non-autistic youth. Both autistic and non-autistic youth appear to experience RM system benefits marked by large gains in listening-in-noise performance. Thus, the use of this technology in educational and other noisy settings where speech perception needs enhancement might be beneficial for both groups of children.

Neural Correlates of Audiovisual Speech Processing in Autistic and Non-Autistic Youth.

Autistic youth demonstrate differences in processing multisensory information, particularly in temporal processing of multisensory speech. Extensive research has identified several key brain regions for multisensory speech processing in non-autistic adults, including the superior temporal sulcus (STS) and insula, but it is unclear to what extent these regions are involved in temporal processing of multisensory speech in autistic youth. As a first step in exploring the neural substrates of multisensory temporal processing in this clinical population, we employed functional magnetic resonance imaging (fMRI) with a simultaneity-judgment audiovisual speech task. Eighteen autistic youth and a comparison group of 20 non-autistic youth matched on chronological age, biological sex, and gender participated. Results extend prior findings from studies of non-autistic adults, with non-autistic youth demonstrating responses in several similar regions as previously implicated in adult temporal processing of multisensory speech. Autistic youth demonstrated responses in fewer of the multisensory regions identified in adult studies; responses were limited to visual and motor cortices. Group responses in the middle temporal gyrus significantly interacted with age; younger autistic individuals showed reduced MTG responses whereas older individuals showed comparable MTG responses relative to non-autistic controls. Across groups, responses in the precuneus covaried with task accuracy, and anterior temporal and insula responses covaried with nonverbal IQ. These preliminary findings suggest possible differences in neural mechanisms of audiovisual processing in autistic youth while highlighting the need to consider participant characteristics in future, larger-scale studies exploring the neural basis of multisensory function in autism.

Associations Between Caregiver Stress and Language Outcomes in Infants With Autistic and Non-Autistic Siblings: An Exploratory Study.

PURPOSE: Caregivers of autistic children present with high stress levels, which have been associated with poorer child outcomes in several domains, including language development. However, prior to this study, it was unknown whether elevated caregiver stress was associated with language development in infant siblings of autistic children (Sibs-autism), who are at increased likelihood of receiving a future diagnosis of autism and/or language impairment compared to infant siblings of non-autistic children. This study explored the degree to which, as well as the mechanisms by which, caregiver stress was linked with later language outcomes of Sibs-autism and infant siblings of non-autistic children (Sibs-NA). METHOD: Participants were 50 infants (28 Sibs-autism; 22 Sibs-NA) aged 12-18 months at the first time point in this study (Time 1). Infants were seen again 9 months later, at 21-27 months of age (Time 2). Caregiver stress was measured via a validated self-report measure at Time 1. Caregiver language input, the putative mechanism by which caregiver stress may influence later language outcomes, was collected via two daylong recordings from digital recording (Language ENvironment Analysis) devices worn by the child at this same time point. Child language outcomes were measured via standardized and caregiver report measures at Time 2. RESULTS: Several models testing hypothesized indirect effects of caregiver stress on later child language outcomes through caregiver language input were statistically significant. Specifically, significant indirect effects suggest that (a) caregivers with increased stress tend to speak less to their infants, and (b) this reduced language input tends to covary with reduced child language outcomes later in life for Sibs-autism and Sibs-NA. CONCLUSIONS: This study provides new insights into links between caregiver stress, caregiver language input, and language outcomes in Sibs-autism and Sibs-NA. Further work is necessary to understand how to best support caregivers and optimize the language learning environments for infants. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.21714368.

The Stability and Validity of Automated Indices of Vocal Development in Infants With Autistic and Non-Autistic Siblings.

PURPOSE: This study evaluates the extent to which automated indices of vocal development are stable and valid for predicting language in infants at increased familial likelihood for autism and/or language impairment and relatively lower likelihood infants. METHOD: A group of infants with autistic siblings (Sibs-autism; 20 infants) and a comparison group of infants with non-autistic siblings (Sibs-NA; 20 infants) wore Language ENvironment Analysis (LENA) recording devices for 16 hr on 2 days within a 1-week period. Extant software was used to derive several putative indices of vocal development from these recordings. Stability of these variables was examined across and within groups. Expressive and receptive language aggregates were calculated for each participant. Multiple regression analyses were used to (a) evaluate zero-order correlations for variables derived from LENA recordings with concurrent and future language and (b) test whether those associations were moderated by group status. RESULTS: Both stability and validity differed by variable and group status. All variables reached acceptable stability in the Sibs-autism group within two to three observations, whereas stability of most variables was attenuated in the Sibs-NA group. No variables were associated with concurrent language in the theoretically motivated direction across groups, but two variables were strongly associated with concurrent expressive language in only the Sibs-NA group. Additionally, two variables were associated with later expressive language, though these correlations were again stronger in the Sibs-NA versus Sibs-autism group. CONCLUSIONS: Although selected automated indices of vocal development were stable in Sibs-autism and/or valid for predicting expressive language within Sibs-NA, no scores showed strong, theoretically motivated associations with language within the Sibs-autism group. Automated indices of vocal development may, thus, have limited validity or clinical utility for predicting language development in infants at elevated familial likelihood for autism. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24415735.

Autism intervention meta-analysis of early childhood studies (Project AIM): updated systematic review and secondary analysis.

OBJECTIVE: To summarize the breadth and quality of evidence supporting commonly recommended early childhood autism interventions and their estimated effects on developmental outcomes. DESIGN: Updated systematic review and meta-analysis (autism intervention meta-analysis; Project AIM). DATA SOURCES: A search was conducted in November 2021 (updating a search done in November 2017) of the following databases and registers: Academic Search Complete, CINAHL Plus with full text, Education Source, Educational Administration Abstracts, ERIC, Medline, ProQuest Dissertations and Theses, PsycINFO, Psychology and Behavioral Sciences Collection, and SocINDEX with full text, Trials, and ClinicalTrials.gov. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Any controlled group study testing the effects of any non-pharmacological intervention on any outcome in young autistic children younger than 8 years. REVIEW METHODS: Newly identified studies were integrated into the previous dataset and were coded for participant, intervention, and outcome characteristics. Interventions were categorized by type of approach (such as behavioral, developmental, naturalistic developmental behavioral intervention, and technology based), and outcomes were categorized by domain (such as social communication, adaptive behavior, play, and language). Risks of bias were evaluated following guidance from Cochrane. Effects were estimated for all intervention and outcome types with sufficient contributing data, stratified by risk of bias, using robust variance estimation to account for intercorrelation of effects within studies and subgroups. RESULTS: The search yielded 289 reports of 252 studies, representing 13 304 participants and effects for 3291 outcomes. When contributing effects were restricted to those from randomized controlled trials, significant summary effects were estimated for behavioral interventions on social emotional or challenging behavior outcomes (Hedges' g=0.58, 95% confidence interval 0.11 to 1.06; P=0.02), developmental interventions on social communication (0.28, 0.12 to 0.44; P=0.003); naturalistic developmental behavioral interventions on adaptive behavior (0.23, 0.02 to 0.43; P=0.03), language (0.16, 0.01 to 0.31; P=0.04), play (0.19, 0.02 to 0.36; P=0.03), social communication (0.35, 0.23 to 0.47; P<0.001), and measures of diagnostic characteristics of autism (0.38, 0.17 to 0.59; P=0.002); and technology based interventions on social communication (0.33, 0.02 to 0.64; P=0.04) and social emotional or challenging behavior outcomes (0.57, 0.04 to 1.09; P=0.04). When effects were further restricted to exclude caregiver or teacher report outcomes, significant effects were estimated only for developmental interventions on social communication (0.31, 0.13 to 0.49; P=0.003) and naturalistic developmental behavioral interventions on social communication (0.36, 0.23 to 0.49; P<0.001) and measures of diagnostic characteristics of autism (0.44, 0.20 to 0.68; P=0.002). When effects were then restricted to exclude those at high risk of detection bias, only one significant summary effect was estimated-naturalistic developmental behavioral interventions on measures of diagnostic characteristics of autism (0.30, 0.03 to 0.57; P=0.03). Adverse events were poorly monitored, but possibly common. CONCLUSION: The available evidence on interventions to support young autistic children has approximately doubled in four years. Some evidence from randomized controlled trials shows that behavioral interventions improve caregiver perception of challenging behavior and child social emotional functioning, and that technology based interventions support proximal improvements in specific social communication and social emotional skills. Evidence also shows that developmental interventions improve social communication in interactions with caregivers, and naturalistic developmental behavioral interventions improve core challenges associated with autism, particularly difficulties with social communication. However, potential benefits of these interventions cannot be weighed against the potential for adverse effects owing to inadequate monitoring and reporting.

The Processing of Audiovisual Speech Is Linked with Vocabulary in Autistic and Nonautistic Children: An ERP Study.

Explaining individual differences in vocabulary in autism is critical, as understanding and using words to communicate are key predictors of long-term outcomes for autistic individuals. Differences in audiovisual speech processing may explain variability in vocabulary in autism. The efficiency of audiovisual speech processing can be indexed via amplitude suppression, wherein the amplitude of the event-related potential (ERP) is reduced at the P2 component in response to audiovisual speech compared to auditory-only speech. This study used electroencephalography (EEG) to measure P2 amplitudes in response to auditory-only and audiovisual speech and norm-referenced, standardized assessments to measure vocabulary in 25 autistic and 25 nonautistic children to determine whether amplitude suppression (a) differs or (b) explains variability in vocabulary in autistic and nonautistic children. A series of regression analyses evaluated associations between amplitude suppression and vocabulary scores. Both groups demonstrated P2 amplitude suppression, on average, in response to audiovisual speech relative to auditory-only speech. Between-group differences in mean amplitude suppression were nonsignificant. Individual differences in amplitude suppression were positively associated with expressive vocabulary through receptive vocabulary, as evidenced by a significant indirect effect observed across groups. The results suggest that efficiency of audiovisual speech processing may explain variance in vocabulary in autism.

A Randomized Controlled Trial for Audiovisual Multisensory Perception in Autistic Youth.

Differences in audiovisual integration are commonly observed in autism. Temporal binding windows (TBWs) of audiovisual speech can be trained (i.e., narrowed) in non-autistic adults; this study evaluated a computer-based perceptual training in autistic youth and assessed whether treatment outcomes varied according to individual characteristics. Thirty autistic youth aged 8-21 were randomly assigned to a brief perceptual training (n = 15) or a control condition (n = 15). At post-test, the perceptual training group did not differ, on average, on TBWs for trained and untrained stimuli and perception of the McGurk illusion compared to the control group. The training benefited youth with higher language and nonverbal IQ scores; the training caused widened TBWs in youth with co-occurring cognitive and language impairments.

Nanoparticle stereochemistry-dependent endocytic processing improves in vivo mRNA delivery.

Stereochemistry can alter small-molecule pharmacokinetics, safety and efficacy. However, it is unclear whether the stereochemistry of a single compound within a multicomponent colloid such as a lipid nanoparticle (LNP) can influence its activity in vivo. Here we report that LNPs containing stereopure 20α-hydroxycholesterol (20α) delivered mRNA to liver cells up to 3-fold more potently than LNPs containing a mixture of both 20α- and 20ß-hydroxycholesterols (20mix). This effect was not driven by LNP physiochemical traits. Instead, in vivo single-cell RNA sequencing and imaging revealed that 20mix LNPs were sorted into phagocytic pathways more than 20α LNPs, resulting in key differences between LNP biodistribution and subsequent LNP functional delivery. These data are consistent with the fact that nanoparticle biodistribution is necessary, but not sufficient, for mRNA delivery, and that stereochemistry-dependent interactions between LNPs and target cells can improve mRNA delivery.

Examining the Latent Structure and Correlates of Sensory Reactivity in Autism: A Multi-site Integrative Data Analysis by the Autism Sensory Research Consortium.

Background Differences in responding to sensory stimuli, including sensory hyperreactivity (HYPER), hyporeactivity (HYPO), and sensory seeking (SEEK) have been observed in autistic individuals across sensory modalities, but few studies have examined the structure of these "supra-modal" traits in the autistic population. Methods Leveraging a combined sample of 3,868 autistic youth drawn from 12 distinct data sources (ages 3-18 years and representing the full range of cognitive ability), the current study used modern psychometric and meta-analytic techniques to interrogate the latent structure and correlates of caregiver-reported HYPER, HYPO, and SEEK within and across sensory modalities. Bifactor statistical indices were used to both evaluate the strength of a "general response pattern" factor for each supra-modal construct and determine the added value of "modality-specific response pattern" scores (e.g., Visual HYPER). Bayesian random-effects integrative data analysis models were used to examine the clinical and demographic correlates of all interpretable HYPER, HYPO and SEEK (sub)constructs. Results All modality-specific HYPER subconstructs could be reliably and validly measured, whereas certain modality-specific HYPO and SEEK subconstructs were psychometrically inadequate when measured using existing items. Bifactor analyses unambiguously supported the validity of a supra-modal HYPER construct (ω H = .800), whereas a coherent supra-modal HYPO construct was not supported (ω H = .611), and supra-modal SEEK models suggested a more limited version of the construct that excluded some sensory modalities (ω H = .799; 4/7 modalities). Within each sensory construct, modality-specific subscales demonstrated substantial added value beyond the supra-modal score. Meta-analytic correlations varied by construct, although sensory features tended to correlate most strongly with other domains of core autism features and co-occurring psychiatric symptoms. Certain subconstructs within the HYPO and SEEK domains were also associated with lower adaptive behavior scores. Limitations: Conclusions may not be generalizable beyond the specific pool of items used in the current study, which was limited to parent-report of observable behaviors and excluded multisensory items that reflect many "real-world" sensory experiences. Conclusion Psychometric issues may limit the degree to which some measures of supra-modal HYPO/SEEK can be interpreted. Depending on the research question at hand, modality-specific response pattern scores may represent a valid alternative method of characterizing sensory reactivity in autism.

Examining the latent structure and correlates of sensory reactivity in autism: a multi-site integrative data analysis by the autism sensory research consortium.

BACKGROUND: Differences in responding to sensory stimuli, including sensory hyperreactivity (HYPER), hyporeactivity (HYPO), and sensory seeking (SEEK) have been observed in autistic individuals across sensory modalities, but few studies have examined the structure of these "supra-modal" traits in the autistic population. METHODS: Leveraging a combined sample of 3868 autistic youth drawn from 12 distinct data sources (ages 3-18 years and representing the full range of cognitive ability), the current study used modern psychometric and meta-analytic techniques to interrogate the latent structure and correlates of caregiver-reported HYPER, HYPO, and SEEK within and across sensory modalities. Bifactor statistical indices were used to both evaluate the strength of a "general response pattern" factor for each supra-modal construct and determine the added value of "modality-specific response pattern" scores (e.g., Visual HYPER). Bayesian random-effects integrative data analysis models were used to examine the clinical and demographic correlates of all interpretable HYPER, HYPO, and SEEK (sub)constructs. RESULTS: All modality-specific HYPER subconstructs could be reliably and validly measured, whereas certain modality-specific HYPO and SEEK subconstructs were psychometrically inadequate when measured using existing items. Bifactor analyses supported the validity of a supra-modal HYPER construct (ωH = .800) but not a supra-modal HYPO construct (ωH = .653), and supra-modal SEEK models suggested a more limited version of the construct that excluded some sensory modalities (ωH = .800; 4/7 modalities). Modality-specific subscales demonstrated significant added value for all response patterns. Meta-analytic correlations varied by construct, although sensory features tended to correlate most with other domains of core autism features and co-occurring psychiatric symptoms (with general HYPER and speech HYPO demonstrating the largest numbers of practically significant correlations). LIMITATIONS: Conclusions may not be generalizable beyond the specific pool of items used in the current study, which was limited to caregiver report of observable behaviors and excluded multisensory items that reflect many "real-world" sensory experiences. CONCLUSION: Of the three sensory response patterns, only HYPER demonstrated sufficient evidence for valid interpretation at the supra-modal level, whereas supra-modal HYPO/SEEK constructs demonstrated substantial psychometric limitations. For clinicians and researchers seeking to characterize sensory reactivity in autism, modality-specific response pattern scores may represent viable alternatives that overcome many of these limitations.

The Impact of Singing on Visual and Multisensory Speech Perception in Children on the Autism Spectrum.

Autistic children show reduced multisensory integration of audiovisual speech stimuli in response to the McGurk illusion. Previously, it has been shown that adults can integrate sung McGurk tokens. These sung speech tokens offer more salient visual and auditory cues, in comparison to the spoken tokens, which may increase the identification and integration of visual speech cues in autistic children. Forty participants (20 autism, 20 non-autistic peers) aged 7-14 completed the study. Participants were presented with speech tokens in four modalities: auditory-only, visual-only, congruent audiovisual, and incongruent audiovisual (i.e., McGurk; auditory 'ba' and visual 'ga'). Tokens were also presented in two formats: spoken and sung. Participants indicated what they perceived via a four-button response box (i.e., 'ba', 'ga', 'da', or 'tha'). Accuracies and perception of the McGurk illusion were calculated for each modality and format. Analysis of visual-only identification indicated a significant main effect of format, whereby participants were more accurate in sung versus spoken trials, but no significant main effect of group or interaction effect. Analysis of the McGurk trials indicated no significant main effect of format or group and no significant interaction effect. Sung speech tokens improved identification of visual speech cues, but did not boost the integration of visual cues with heard speech across groups. Additional work is needed to determine what properties of spoken speech contributed to the observed improvement in visual accuracy and to evaluate whether more prolonged exposure to sung speech may yield effects on multisensory integration.

Inflexible Updating of the Self-Other Divide During a Social Context in Autism: Psychophysical, Electrophysiological, and Neural Network Modeling Evidence.

BACKGROUND: Autism spectrum disorder (ASD) affects many aspects of life, from social interactions to (multi)sensory processing. Similarly, the condition expresses at a variety of levels of description, from genetics to neural circuits and interpersonal behavior. We attempt to bridge between domains and levels of description by detailing the behavioral, electrophysiological, and putative neural network basis of peripersonal space (PPS) updating in ASD during a social context, given that the encoding of this space relies on appropriate multisensory integration, is malleable by social context, and is thought to delineate the boundary between the self and others. METHODS: Fifty (20 male/30 female) young adults, either diagnosed with ASD or age- and sex-matched individuals, took part in a visuotactile reaction time task indexing PPS, while high-density electroencephalography was continuously recorded. Neural network modeling was performed in silico. RESULTS: Multisensory psychophysics demonstrates that while PPS in neurotypical individuals shrinks in the presence of others-as to "give space"-this does not occur in ASD. Likewise, electroencephalography recordings suggest that multisensory integration is altered by social context in neurotypical individuals but not in individuals with ASD. Finally, a biologically plausible neural network model shows, as a proof of principle, that PPS updating may be inflexible in ASD owing to the altered excitatory/inhibitory balance that characterizes neural circuits in animal models of ASD. CONCLUSIONS: Findings are conceptually in line with recent statistical inference accounts, suggesting diminished flexibility in ASD, and further these observations by suggesting within an example relevant for social cognition that such inflexibility may be due to excitatory/inhibitory imbalances.