Applying a User-Centered Design Framework to Develop a Remote Research Assessment Protocol for a Randomized Clinical Trial for Toddlers with Early Autism Characteristics.

COVID-19 required many research teams to shift from in-person to remote assessments, which posed both procedural and theoretical challenges. While research has explored the utility of remote assessments for autism diagnosis from the perspective of families and clinicians, less is known about their application in clinical trials. This paper describes the development of a remote research assessment protocol for a randomized clinical trial focusing on the implementation of reciprocal imitation teaching (RIT) with toddlers in Part C early intervention. This project spans two phases. For Phase 1, our team developed and documented a series of steps utilizing user-centered design (UCD) strategies (e.g., recruiting potential users, creating a prototype, engaging in iterative development) for the purpose of redesigning an assessment protocol for a remote environment. For Phase 2, we examined preliminary outcomes of the redesign process. Primary end users (assessors) rated post-redesign usability and acceptability, while acceptability was examined using attrition data from secondary end users (family participants). Preliminary fidelity of implementation was also examined. The iterative redesign process allowed the research team to refine aspects of the assessment that ultimately led to promising preliminary ratings of usability, acceptability, and feasibility, as well as high fidelity. Preliminary data suggest that the redesigned assessment appears to be an acceptable, feasible, and usable tool for autism clinical trial research and that assessors can use it with fidelity. Further research is needed to examine the reliability and validity of the assessment, as well as implementation characteristics on a larger scale.

Reciprocal Associations Between Language Ability and Social Functioning Development in Pre-verbal Autistic Children.

Longitudinal research on language abilities and social functioning in young children suggests that gains in one domain affect gains in the other. However, few studies have examined inter-relations of language and social functioning jointly among young children diagnosed with autism spectrum disorder (ASD). Pre-verbal toddlers with ASD are a group of particular clinical relevance, given that greater language abilities at school entry have been associated with positive long-term adjustment in many areas, including adaptive and social functioning. Reduced attention to and engagement in social interactions among autistic toddlers who are not yet speaking may interfere with language development concurrently and over time. The present study examined reciprocal associations between language ability and social functioning over a 2-year period across three time points in a sample of 90 pre-verbal autistic toddlers using cross-lagged panel analyses conducted in MPlus. Cross-lagged panel analyses revealed significant within-timepoint synchronous correlations, within-domain autoregressive paths over time, and as hypothesized, reciprocal significance in all cross-lagged paths. For very young pre-verbal children with ASD, language ability and social functioning appear to exert concurrent and cascading developmental influences on one another. Targeting both language and social functioning simultaneously may enhance intervention efficacy for very young pre-verbal children with ASD.

Normalization of brain morphology after surgery in sagittal craniosynostosis.

OBJECT Nonsyndromic craniosynostosis (NSC) is associated with significant learning disability later in life. Surgical reconstruction is typically performed before 1 year of age to correct the cranial vault morphology and to allow for normalized brain growth with the goal of improving cognitive function. Yet, no studies have assessed to what extent normalized brain growth is actually achieved. Recent advances in MRI have allowed for automated methods of objectively assessing subtle and pronounced brain morphological differences. The authors used one such technique, deformation-based morphometry (DBM) Jacobian mapping, to determine how previously treated adolescents with sagittal NSC (sNSC) significantly differ in brain anatomy compared with healthy matched controls up to 11.5 years after surgery. METHODS Eight adolescent patients with sNSC, previously treated via whole-vault cranioplasty at a mean age of 7 months, and 8 age- and IQ-matched control subjects without craniosynostosis (mean age for both groups = 12.3 years), underwent functional 3-T MRI. Statistically significant group tissue-volume differences were assessed using DBM, a whole-brain technique that estimates morphological differences between 2 groups at each voxel (p < 0.01). Group-wise Jacobian volume maps were generated using a spacing of 1.5 mm and a resolution of 1.05 × 1.05 × 1.05 mm(3). RESULTS There were no significant areas of volume reduction or expansion in any brain areas in adolescents with sNSC compared with controls at a significance level of p < 0.01. At the more liberal threshold of p < 0.05, two areas of brain expansion extending anteroposteriorly in the right temporooccipital and left frontoparietal regions appeared in patients with sNSC compared with controls. CONCLUSIONS Compared with previous reports on untreated infants with sNSC, adolescents with sNSC in this cohort had few areas of brain dysmorphology many years after surgery. This result suggests that comprehensive cranioplasty performed at an early age offers substantial brain normalization by adolescence, but also that some effects of vault constriction may still persist after treatment. Specifically, few areas of expansion in frontoparietal and temporooccipital regions may persist. Overall, data from this small cohort support the primary goal of surgery in allowing for more normalized brain growth. Larger samples, and correlating degree of normalization with cognitive performance in NSC, are warranted.

Toward optimal outcome following pivotal response treatment: a case series.

There is a growing literature on children with autism spectrum disorder (ASD) who respond favorably to behavioral treatment, which is often termed "optimal outcome." Rates and definitions of optimal outcome vary widely. The current case series describes an empirically validated behavioral treatment approach called Pivotal Response Treatment (PRT). We present two preschool-aged children who received an intensive course of PRT and seem to be on a trajectory toward potential optimal outcome. Understanding response to treatment and predictors of response is crucial, not necessarily to predict who may succeed, but to individualize medicine and match children with customized treatment programs that will be best tailored to their unique and varied needs.

Pivotal Response Treatment: Case Reports.

The current paper provides an overview of an evidence-based treatment, Pivotal Response Treatment (PRT), for autism spectrum disorder (ASD). The paper describes PRT principles and then illustrates the approach using two case reports. The children are preschool-aged children with high-functioning ASD. They were participating in a four-month clinical trial of PRT. At the start of treatment, they presented with significant social communication impairments, including a minimal understanding of reciprocity, limited play skills, and repetitive behaviors and speech. The paper outlines how behavioral treatment goals were identified and then how activities were designed, using principles of PRT, to target skill acquisition. Following the treatment course, both children made substantial and meaningful gains in social communication skill development.

Heterogeneity of neural mechanisms of response to pivotal response treatment.

We investigated the mechanisms by which Pivotal Response Treatment (PRT) improves social communication in a case series of 10 preschool-aged children with Autism Spectrum Disorder (ASD). Functional magnetic resonance imaging (fMRI) identified brain responses during a biological motion perception task conducted prior to and following 16 weeks of PRT treatment. Overall, the neural systems supporting social perception in these 10 children were malleable through implementation of PRT; following treatment, neural responses were more similar to those of typically developing children (TD). However, at baseline, half of the children exhibited hypoactivation, relative to a group of TD children, in the right posterior superior temporal sulcus (pSTS), and half exhibited hyperactivation in this region. Strikingly, the groups exhibited differential neural responses to treatment: The five children who exhibited hypoactivation at baseline evidenced increased activation in components of the reward system including the ventral striatum and putamen. The five children who exhibited hyperactivation at baseline evidenced decreased activation in subcortical regions critical for regulating the flow of stimulation and conveying signals of salience to the cortex-the thalamus, amygdala, and hippocampus. Our results support further investigation into the differential effects of particular treatment strategies relative to specific neural targets. Identification of treatment strategies that address the patterns of neural vulnerability unique to each patient is consistent with the priority of creating individually tailored interventions customized to the behavioral and neural characteristics of a given person.

Improvements in social and adaptive functioning following short-duration PRT program: a clinical replication.

Pivotal Response Treatment (PRT) is an empirically validated behavioral treatment for individuals with autism spectrum disorders (ASD). The purpose of the current study was to assess the efficacy of PRT for ten cognitively-able preschool-aged children with ASD in the context of a short-duration (4-month) treatment model. Most research on PRT used individual behavioral goals as outcome measures, but the current study utilized standardized assessments of broader-based social communication and adaptive skills. The children made substantial gains; however, magnitude and consistency of response across measures were variable. The results provide additional support for the efficacy of PRT as well as evidence for improvements in higher-order social communication and adaptive skill development within the context of a short-duration PRT model.

Brain mechanisms of plasticity in response to treatments for core deficits in autism.

Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by social communication impairments and repetitive behaviors. Although the prevalence of ASD is estimated at 1 in 88, understanding of the neural mechanisms underlying the disorder is still emerging. Regions including the amygdala, superior temporal sulcus, orbitofrontal cortex, fusiform gyrus, medial prefrontal cortex, and insula have been implicated in social processing. Neuroimaging studies have demonstrated both anatomical and functional differences in these areas of the brain in individuals with ASD when compared to controls; however, research on the neural basis for response to treatment in ASD is limited. Results of the three studies that have examined the neural mechanisms underlying treatment response are promising; following treatment, the brains of individuals with ASD seem to "normalize," responding more similarly to those of typically developing individuals. The research in this area is in its early stages, and thus a focused effort examining the neural basis of treatment response in ASD is crucial.