Refining our Understanding of Anxiety in Autistic Youth: Examining the Role of Behavioral Inflexibility.

Prior research has demonstrated that cognitive inflexibility is associated with anxiety in autistic individuals. Everyday patterns of behavioral inflexibility (e.g. observable inflexible behavior in the context of the need to change or adapt and that is manifested in real-world everyday settings) is common in autism and can be distinguished from performance on discrete cognitive tasks that tap flexible attention, learning, or decision-making. The purpose of this study was to extend this prior work on inflexibility in autism but with measures specifically developed with input from stakeholders (caregivers and clinicians) for autistic youth designed to measure everyday behavioral inflexibility (BI). We characterized anxiety in a large sample of autistic (N = 145) and non-autistic youth (N = 91), ages 3 to 17 years, using the Parent Rated Anxiety Scale for Autism Spectrum Disorder (PRAS-ASD). Further, we sought to understand how BI, measured via the Behavioral Inflexibility Scale (BIS), predicted anxiety compared to other variables known to increase anxiety in youth (chronological age, IQ, autism diagnosis, assigned sex at birth). Autistic youth had higher parent-related anxiety and BI compared to non-autistic youth. BI was the strongest predictor of anxiety scores, irrespective of diagnosis. Overall, our findings highlight the importance of BI to the understanding of anxiety in autistic youth.

Evaluating the Feasibility of The NIH Toolbox Cognition Battery for Autistic Children and Adolescents.

This study evaluates the feasibility of the NIH Toolbox Cognition Battery (NIH-TCB) for use in autism spectrum disorder (ASD). 116 autistic children and adolescents and 80 typically developing (TD) controls, ages 3-17 years, completed four NIH-TCB tasks related to inhibitory control, cognitive flexibility, processing speed, and episodic memory. While the majority of autistic and TD children completed all four tasks, autistic children experienced greater difficulties with task completion. Across autistic and TD children, performance on NIH-TCB tasks was highly dependent on IQ, but significant performance differences related to ASD diagnosis were found for two of four tasks. These findings highlight the potential strengths and limitations of the NIH-TCB for use with autistic children.

Resting-state hippocampal networks related to language processing reveal unique patterns in temporal lobe epilepsy.

OBJECTIVE: Patients with temporal lobe epilepsy (TLE) commonly experience a broad range of language impairments. These deficits are thought to arise from repeated seizure activity that damages language regions. However, connectivity between the seizure onset region in the hippocampus and regions related to language processing has rarely been studied, and could also have a strong impact on language function. The purpose of this study was to use resting-state functional connectivity (FC) measures to assess hippocampal network patterns and their relation to language abilities in patients with right TLE (RLTE), left TLE (LTLE), and healthy controls. METHODS: Presurgical resting-state 3T functional MRI data were acquired from 40 patients with mesial TLE (27 RTLE, 13 LTLE) and 54 controls. The regions of interest were the anterior and posterior bilateral hippocampi and eleven regions grouped by frontal or temporo-parietal locations, including large areas of language-related cortex. FC values were computed with the right/left anterior and posterior hippocampi as the seeds and frontal and temporo-parietal regions as targets. Resting-state lateralization indices were also calculated (LI-Rest), and all FC measures were correlated to neuropsychological language scores and measures related to manifestation of epilepsy including age of onset, duration of disease, monthly seizure frequency, and hippocampal volume. RESULTS: We found significant group differences between the anterior hippocampi and temporo-parietal regions closest to the seizure focus, in which RTLE and LTLE showed stronger connectivity to their contralateral hippocampus, while controls showed similar connectivity to both hippocampi. In addition, LI-Rest demonstrated significantly more right lateralization in LTLE compared to RTLE for temporo-parietal regions only. In LTLE, we found significant associations between stronger hippocampal network resting-state FC and later age of onset and decreased left anterior hippocampal volume. SIGNIFICANCE: The results of our study indicate that the presence of TLE impacts hippocampal-temporo-parietal networks relevant to language processing.

Children With Autism Produce a Unique Pattern of EEG Microstates During an Eyes Closed Resting-State Condition.

Although fMRI studies have produced considerable evidence for differences in the spatial connectivity of resting-state brain networks in persons with autism spectrum disorder (ASD) relative to typically developing (TD) peers, little is known about the temporal dynamics of these brain networks in ASD. The aim of this study was to examine the EEG microstate architecture in children with ASD as compared to TD at rest in two separate conditions - eyes-closed (EC) and eyes-open (EO). EEG microstate analysis was performed on resting-state data of 13 ASD and 13 TD children matched on age, gender, and IQ. We found that children with ASD and TD peers produced topographically similar canonical microstates at rest. Group differences in the duration and frequency of these microstates were found primarily in the EC resting-state condition. In line with previous fMRI findings that have reported differences in spatial connectivity within the salience network (previously correlated with the activity of microstate C) in ASD, we found that the duration of activation of microstate C was increased, and the frequency of microstate C was decreased in ASD as compared to TD in EC resting-state. Functionally, these results may be reflective of alterations in interoceptive processes in ASD. These results suggest a unique pattern of EEG microstate architecture in ASD relative to TD during resting-states and also that EEG microstate parameters in ASD are susceptible to differences in resting-state conditions.

Auditory event-related potentials index faster processing of natural speech but not synthetic speech over nonspeech analogs in children.

Given the crucial role of speech sounds in human language, it may be beneficial for speech to be supported by more efficient auditory and attentional neural processing mechanisms compared to nonspeech sounds. However, previous event-related potential (ERP) studies have found either no differences or slower auditory processing of speech than nonspeech, as well as inconsistent attentional processing. We hypothesized that this may be due to the use of synthetic stimuli in past experiments. The present study measured ERP responses during passive listening to both synthetic and natural speech and complexity-matched nonspeech analog sounds in 22 8-11-year-old children. We found that although children were more likely to show immature auditory ERP responses to the more complex natural stimuli, ERP latencies were significantly faster to natural speech compared to cow vocalizations, but were significantly slower to synthetic speech compared to tones. The attentional results indicated a P3a orienting response only to the cow sound, and we discuss potential methodological reasons for this. We conclude that our results support more efficient auditory processing of natural speech sounds in children, though more research with a wider array of stimuli will be necessary to confirm these results. Our results also highlight the importance of using natural stimuli in research investigating the neurobiology of language.

Development of the Behavioral Inflexibility Scale for Children with Autism Spectrum Disorder and Other Developmental Disabilities.

Behavior inflexibility (BI) refers to rigid patterns of behavior that contrast with the need to be adaptable to changing environmental demands. We developed a parent-reported outcome measure of BI for children with autism spectrum disorder (ASD) and other developmental disabilities with a multi-step iterative process. A pool of 62 candidate items was generated through expert panel feedback, review of existing scales and focus groups. A consensus process was used to generate the final 38 items. Parents of 943 children (age range, 3-18 years; average, 11.4 years; 79% boys) with ASD completed an online survey. One hundred thirty-three parents rated their child twice within 3 weeks (average = 16.5 days). A series of factor analyses suggested that the 38 items measured a single construct. Scores had a weak correlation with level of functioning (-0.12) and did not differ based on sex. Scores had a negligible correlation with age (-0.07), although measurement invariance was not supported. The mean total score for the Behavioral Inflexibility Scale (BIS) was normally distributed. Internal consistency was α = 0.97 and temporal stability was r = 0.92. Correlations with parent ratings on the subscales of the Repetitive Behavior Scale-Revised varied from 0.48 to 0.89. The correlation with parent ratings on the Social Communication Questionnaire total score was 0.52. Our data show that BI in children with ASD ranges significantly from mild to severe and that the 38-item BIS is valid and reliable. Autism Res 2020, 13: 489-499. © 2020 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc. LAY SUMMARY: We developed a parent-completed rating scale of behavior inflexibility (BI) for children with developmental disabilities using a multistep process. The Behavioral Inflexibility Scale (BIS) contains 38 questions rated on a 6-point scale. Parents of 943 children with autism spectrum disorder (ASD) completed an online survey. We examined associations between the BIS and other scales and demographic variables. The BIS is valid and reliable. BI in children with ASD ranges from mild to severe.

Parent and professional perspectives on behavioral inflexibility in autism spectrum disorders: A qualitative study.

Restricted and repetitive behaviors are a core feature of autism spectrum disorder; however, research on the functional impact of these behaviors on the quality of life for individuals with autism spectrum disorder and their families remains scarce. We conducted focus groups with parents of children with autism spectrum disorder and clinicians in order to better characterize the functional impact of behavioral inflexibility, which represents one potential dimensional construct that could account for the breadth of behaviors comprising the restricted and repetitive behavior domain. Transcripts of the focus groups were analyzed using qualitative analysis coding methods to determine parent and clinician beliefs on a range of issues related to behavioral inflexibility including overall impact, types of child behaviors, and strategies for managing behavioral inflexibility. Thematic analysis revealed that parents and clinicians view behavioral inflexibility as an important behavior that impacts multiple areas of functioning, relates to other restricted and repetitive behaviors as well as social communication behaviors, and warrants targeted treatment. Notably, many parents and clinicians emphasized some positive consequences of behavioral inflexibility as well. These findings add crucial insights into the functional impact of behavioral inflexibility and restricted and repetitive behaviors as a whole and suggest that behavioral inflexibility represents an important avenue for future research.

Subgrouping Autism Based on Symptom Severity Leads to Differences in the Degree of Convergence Between Core Feature Domains.

Existing models of autism spectrum disorder (ASD) disagree as to whether the core features should be conceptualized as convergent (related) or divergent (unrelated), and the few previous studies addressing this question have found conflicting results. We examined standardized parent ratings of symptoms from three domains (social, communication, repetitive behaviors) in large samples of typically developing children, children with ASD, and ASD subgroups. Our results suggest that the most evidence for divergence lies in typically developing children and lower severity ASD cases, while more evidence for convergence is found in a subset of cases with more severe impairment on any core feature. These results highlight the importance of subgrouping ASD given the degree of phenotypic heterogeneity present across the autism spectrum.

Social Orienting and Attention Is Influenced by the Presence of Competing Nonsocial Information in Adolescents with Autism.

Background: Our experiences with the world play a critical role in neural and behavioral development. Children with autism spectrum disorder (ASD) spend a disproportionate amount of time seeking out, attending to, and engaging with aspects of their environment that are largely nonsocial in nature. In this study we adapted an established method for eliciting and quantifying aspects of visual choice behavior related to preference to test the hypothesis that preference for nonsocial sources of stimulation diminishes orientation and attention to social sources of stimulation in children with ASD. Method: Preferential viewing tasks can serve as objective measures of preference, with a greater proportion of viewing time to one item indicative of increased preference. The current task used gaze-tracking technology to examine patterns of visual orientation and attention to stimulus pairs that varied in social (faces) and nonsocial content (high autism interest or low autism interest). Participants included both adolescents diagnosed with ASD and typically developing; groups were matched on IQ and gender. Results: Repeated measures ANOVA revealed that individuals with ASD had a significantly greater latency to first fixate on social images when this image was paired with a high autism interest image, compared to a low autism interest image pairing. Participants with ASD showed greater total look time to objects, while typically developing participants preferred to look at faces. Groups also differed in number and average duration of fixations to social and object images. In the ASD group only, a measure of nonsocial interest was associated with reduced preference for social images when paired with high autism interest images. Conclusions: In ASD, the presence of nonsocial sources of stimulation can significantly increase the latency of look time to social sources of information. These results suggest that atypicalities in social motivation in ASD may be context-dependent, with a greater degree of plasticity than is assumed by existing social motivation accounts of ASD.