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Summary of Advances Cover 2016
Summary of Advance
In Autism Spectrum Disorder Research
Question 4: Which Treatments and Interventions Will Help?

Longitudinal effects of adaptive interventions with a speech-generating device in minimally verbal children with ASD
Almirall D, DiStefano C, Chang YC, Shire S, Kaiser A, Lu X, Nahum-Shani I, Landa R, Mathy P, Kasari C. J Clin Child Adolesc Psychol. 2016 Jul-Aug;45(4):442-56. [PMID: 26954267]

Studies estimate that 25-30% of children with ASD who engage in communication interventions will not achieve spoken communication. Failure to develop spoken language by school-age increases the likelihood of poor longterm outcomes in social functioning. Timing of effective communication intervention is also critical, as there is a developmental window for children to develop communication skills.

Because there is high variability between minimally verbal children with ASD, the progress that each child makes in response to treatment will be different. Treatment that can be adjusted based on the progress of the child is critical for maximizing the effectiveness of the intervention. Therefore, it is important to determine long-term outcomes across different combinations of communication interventions.

In this randomized study of 61 minimally verbal 5- to 8-year-old children with ASD, researchers compared the effectiveness of three adaptive communication interventions over time. All children received joint attention, symbolic play, engagement, and regulation (JASP—a naturalistic developmental behavioral intervention that has been shown to improve social communication outcomes) with enhanced milieu training (EMT—a spoken-language intervention).

A major concern in this field is whether speech generating devices (SGDs) help or hinder progress in communication in this population. Therefore, one component of this study tested JASP+EMT with and without the use of SGDs. To better understand how to accommodate differences in treatment response, another component of this study tested an intensified intervention for children who show a slower response to the treatment.

Each intervention was 24 weeks long and occurred in two stages, as follows:

Intervention 1 (No SGD, No SGD):

Stage 1 – JASP+EMT

Stage 2 – (Responders) Continued JASP + EMT; (Slow Responders) Intensified JASP+EMT

Intervention 2 (No SGD, SGD):

Stage 1 – JASP+EMT

Stage 2 – (Responders) Continued JASP+EMT+SGD; (Slow Responders) Intensified JASP+EMT+SGD

Intervention 3 (SGD, SGD):

Stage 1 – JASP+EMT+SGD

Stage 2 – (Responders) Continued JASP+EMT+SGD; (Slow Responders) Intensified JASP+EMT+SGD

The researchers measured communication skills by verbal outcomes (the total number of spontaneous communicative utterances and the number of different word roots) and nonverbal outcomes (using eye contact or gestures to alert another child to pay attention to an object or request something). For each intervention, all children participated in Stage 1 for the first 12 weeks. If a participant was responsive (improved by 25% or more from baseline scores on verbal and nonverbal communication tests) in the first 12 weeks, they continued with the intervention through Stage 2. If a participant was slow to respond to the Stage 1 intervention, they progressed to an “intensified” treatment (one additional treatment session per week) for Stage 2.

The third intervention, which included SGD in both stages, proved to be the most effective intervention across all outcome measures, showing significant improvement in spontaneous spoken and non-spoken communication. The enhanced effect of adding SGD to the intervention was seen in both the early-responding and the slower-responding groups of children. In addition to improved communication outcomes, the children demonstrated an increased desire to engage in communication during intervention sessions.

These data indicate that SGDs in combination with a development-based behavioral intervention can significantly improve social communication skills in minimally verbal children with ASD. Over time, this improved outcome may positively impact further gains in social functioning.

Preschool deployment of evidence-based social communication intervention: JASPER in the classroom
Chang YC, Shire SY, Shih W, Gelfand C, Kasari C. J Autism Dev Disord. 2016 Jun;46(6):2211-23. [PMID: 26936161]

Early intervention for social and communication skills is important for children with ASD. Most preschool-age children with ASD are taught in public preschools, where they can receive educational and small group support. Although public preschool teachers are provided with strategies to support children with ASD, they often lack specific training for social communication skills, and may have inadequate skills for this developmentally critical intervention.

Social communication skills include joint attention and engagement (the ability to draw another person’s attention to and engage them in an object of shared interest), language skills, and play skills. There has been some evidence that social communication can improve with one-on-one programs, in which the teacher engages directly with only one student. However, one-on-one programs may not be feasible in a public classroom setting, where teachers are typically able to support children with ASD in small groups only.

This study tested the effectiveness of a modified training program for the small group social communication program called JASPER (Joint Attention Symbolic Play Engagement and Regulation). Sixty-six 3- to 5-year-old children with ASD were divided into 12 classrooms. Classrooms were randomized across two groups of children: 1) a group that received an immediate treatment (IT) of JASPER upon entry to the classroom, and 2) a control group that was waitlisted (WL), placed in the usual preschool curriculum, and received JASPER 4 months later. Outcome measures were taken on teachers and students at three time points (at entry into the program, after 2 months of use, and at a 1-month follow-up). Student assessments measured standard social communication, interaction, and play. Teacher assessment included measures to ensure that they were correctly implementing the interventions.

The researchers had three goals: 1) to determine whether children in the IT group showed greater improvement in social communication and engagement skills than children in the WL group; 2) to determine whether children in the IT group would show greater improvement in cognitive and language tests than children in the WL group; and 3) to determine if the modified small group program could be effectively implemented in a classroom setting.

As compared to children in the WL group, children in the IT group showed improvement in initiating social communication and making requests to engage with teachers and children, as measured by the number of times children used phrases such as “Let’s play” or “I want block.” Children in the IT group also showed improvement in use of spontaneous words or phrases, engaged in more complicated forms of play, and increased their use of two- to three-word utterances, as compared to the WL group. Teacher outcomes indicated that trained teachers maintained reliable and effective delivery of JASPER over time.

The results of this study indicate that social engagement interventions such as JASPER can be successfully adapted for small groups within a public school setting. Teachers who are provided with the proper training can effectively implement JASPER so that children with ASD in public preschools can receive much-needed social communication intervention.

Intervention effects on spoken-language outcomes for children with autism: a systematic review and meta-analysis
Hampton LH, Kaiser AP. J Intellect Disabil Res. 2016 May;60(5):444-63. [PMID: 27120988]

Spoken-language delays are common in children with ASD, but studies that investigate the effect of early intervention on ASD symptoms often do not address the effect of intervention on language deficits. However, some research has indicated that early interventions that target play and joint attention skills can improve language outcomes.

The two main types of spoken-language interventions are "targeted" and "comprehensive." Targeted interventions focus on teaching pre-linguistic and communication skills, while comprehensive interventions teach a broad set of skills that are related to the development of spoken-language skills. Both targeted and comprehensive interventions may include parent training, and studies suggest that parent intervention may be just as effective in spoken-language development as clinician-based intervention.

This comprehensive review of 26 original research studies of children with ASD who participated in early intervention was conducted to determine if 1) early interventions improve spoken language in young children with ASD, as compared to usual treatments, 2) the amount of intervention affects spoken-language outcome, 3) adding parent training helps improve spoken-language outcome, and 4) spoken-language outcome is affected by other variables such as the age of the participant or the type of intervention (targeted versus comprehensive).

The studies included in this review met the following criteria: all subjects were English-speaking children that were 8 years old or younger, all studies included behavioral interventions but did not include pharmacological interventions, the outcomes of the studies were determined using standardized spoken-language measures, and the studies included a comparison group that did not receive intervention. The review included data from a total of 1,738 participants with ASD. The average age of the participants was 3.33 years old, and 81% of children were male. Most participants had cognitive scores that indicated comorbid intellectual disabilities. Interventions included direct teaching components and naturalistic teaching components.

Overall, children with ASD improved in spoken-language skills after intervention for ASD symptoms. Of the interventions included, 38% of the studies used parent-guided treatment, 15% of the studies used clinician-guided treatment, and 47% of the studies used treatment that involved both parents and clinicians. Interventions that included both clinicians and parents were more effective than interventions that included only clinician or only parent.

Analyzed together, these studies indicate an improvement equivalent to a 4-point increase on a standard language measure immediately following intervention, and an additional 6-point increase for children that received intervention from both the parent and the clinician, compared to children that received a community intervention.

It is important to note that improvement across these studies is demonstrated for single-word language use but has not been demonstrated for more complex language. In addition, the studies included in this analysis did not include a long-term follow-up, so it is not known whether these effects can be sustained. Improvements in spoken language did not seem to increase with dose of therapy, nor were they dependent on the type of therapy (targeted versus comprehensive).

The main limitation of this comprehensive review is there was not a lot of variability in the degree of intellectual disabilities among the children included in the studies. Therefore, no conclusion can be made about the effect of intervention on spoken-language skills across a range of intellectual disabilities. As a result of the analysis across studies, the researchers propose that 1) both parents and clinicians should be involved in interventions for the greatest benefit, 2) long-term intervention may be needed to maintain the benefit in spoken-language skills, and 3) targeted and comprehensive interventions are equally effective and both can be used to improve spoken language in children with ASD.

Children with autism spectrum disorder and social skills groups at school: a randomized trial comparing intervention approach and peer composition
Kasari C, Dean M, Kretzmann M, Shih W, Orlich F, Whitney R, Landa R, Lord C, King B. J Child Psychol Psychiatry. 2016 Feb;57(2):171-9. [PMID: 26391889]

Children with ASD often struggle to form relationships with their peers, which can impede their ability to form and interact within social networks. Typically developing children form relationships based on propinquity (the tendency to develop friendships with those in close proximity) and homophily (the connection made from shared characteristics such as gender, cultural background, and common interests). Children with ASD, though close in proximity to their classmates, are often isolated as being the only child with ASD. Therefore, even with propinquity acting in their favor, the lack of homophily can present challenges for the development of peer relationships. To address this social development challenge, children with ASD are often enrolled in clinic-based social skills intervention groups, which help children navigate skills such as starting and maintaining a conversation and choosing appropriate friends. However, the clinic-based group setting is not often generalizable to the real world, and the social skills they develop in the clinic may not translate to the school setting, where those skills would have the most impact. Therefore, social skills interventions performed in a school setting may be the most effective way to help children with ASD develop peer relationships.

The goal of this randomized study was to compare two social skills interventions adapted for a school setting, and to compare group composition (children with ASD only versus children with ASD and typically developing children combined). Children ranging from kindergarten to fifth grade participated in either a SKILLS or an ENGAGE intervention program over an 8-week period. The SKILLS intervention was made up of only children with ASD. The SKILLS intervention (a lesson-based approach most likely to be used in a clinical setting) was led by an adult instructor at the school. Children with ASD received a set of interactive lessons on social skills, such as how to handle teasing, nonverbal language, conversation, and friendship tips. The children also received weekly homework assignments. The ENGAGE intervention was randomized to include both children with ASD and typically developing children from the same classroom, and was designed to help children with ASD model friendship-promoting behaviors. In this child-led intervention, the children worked together to set up a daily schedule and engaged in activities that included conversational exercise, structured games, free play, storytelling, and music. Both interventions were evaluated using The Friendship Survey, a questionnaire that students completed before the intervention, at the end of treatment, and 6-8 weeks after the intervention, to assess the children’s friendships and social networks. The researchers also recorded playground observations using the Playground Observation of Peer Engagement tool and “friendship nominations” (the number of times a child with ASD nominated friends and the number of times a classmate nominated a child with ASD as a friend) to determine the extent of their social networks.

The researchers found that on average, both groups showed increased amounts of time spent engaging with other children on the playground. Surprisingly, the SKILLS group more significantly increased time spent with other children and decreased time spent in isolation than the ENGAGE group. The researchers also found that the two interventions benefitted children differently based on their level of behavioral problems and their closeness with their teacher. The SKILLS intervention more greatly benefited children with high behavioral problems and low teacher-child closeness, while the ENGAGE intervention benefitted children with high teacher-child closeness. There was no significant change in friendship nominations as a result of these interventions, suggesting no change in social networks. However, this could be due to the fact that both interventions brought together children from different classrooms, but friendship nominations were only allowed to be made between children of the same classroom.

These results suggest that an adult instructor-based intervention may be most effective in a school setting. This is likely because the SKILLS intervention provided more concrete and direct instruction than the indirect activities in the ENGAGE intervention. Also, by bringing children from different classrooms together and by including only children with ASD in the intervention groups, the SKILLS intervention better met both the propinquity and homophily criteria for relationship development. However, a child with ASD who has fewer behavioral issues and higher closeness to the teacher may benefit from an ENGAGE approach to building social skills.

Parent-mediated social communication therapy for young children with autism (PACT): long-term follow-up of a randomised controlled trial
Pickles A, Le Couteur A, Leadbitter K, Salomone E, Cole-Fletcher R, Tobin H, Gammer I, Lowry J, Vamvakas G, Byford S, Aldred C, Slonims V, McConachie H, Howlin P, Parr JR, Charman T, Green J. Lancet. 2016 Nov 19;388(10059):2501-2509. [PMID: 27793431]

Early intervention is important for reduction of symptoms in children with ASD. Previous studies of early interventions have been limited to short-term follow-up periods, and it is not known if the effect of early intervention is maintained throughout childhood. It is therefore important to study the long-term effectiveness of a parent-mediated social intervention for children with ASD.

PACT (Preschool Autism Communication Trial) is a 1-year social communication intervention for preschool-age children with ASD. PACT consists of 12, 2-hour therapy sessions over 6 months, followed by 6 months of monthly support sessions. In addition, the program includes 20-30-minute parent-led daily activity sessions. In this randomized controlled study, researchers compared outcomes of children with ASD who participated in the PACT program against children with ASD who received treatment as usual.

The children were assessed for the severity of ASD symptoms, parent-child communication, and language skills at three time periods: before the intervention, at the end of the intervention, and at a 6-year follow-up. At the end of the intervention, children who participated in PACT showed significantly greater improvement in ASD symptom severity than the children who received treatment as usual. In addition, children who participated in PACT also showed a greater tendency to initiate parent-child communication, which led to improved communication in general. Notably, this improvement in ASD symptom severity and parent-child communication was sustained over the long-term through the 6-year follow-up. There was no difference in language skills between the two groups.

This is the first study to show long-term effects of a naturalistic developmental intervention for social communication. The researchers proposed that the long-term effect of PACT was due in part to the promotion of parent-child social communication at home, a setting where much of social learning occurs.

Brain responses to biological motion predict treatment outcome in young children with autism
Yang D, Pelphrey KA, Sukhodolsky DG, Crowley MJ, Dayan E, Dvornek NC, Venkataraman A, Duncan J, Staib L, Ventola P. Transl Psychiatry. 2016 Nov 15;6(11):e948. [PMID: 27845779]

Early intervention is critical for improvement of ASD symptoms. However, the constellation of ASD symptoms is complex and diverse across individuals, therefore an intervention that is effective for one person may not be effective for another. Time invested in the wrong treatment may be time wasted, especially during developmentally critical periods. A theoretical solution would be to identify unique markers of biological activity that could predict whether a child would likely respond to a given treatment. This would allow clinicians to identify effective treatments more accurately and efficiently.

Neuroimaging techniques, which allow for visualization of brain activity, have identified brain circuits involved in the social processes that are often altered in ASD. For example, previous studies have identified neural circuits involved in social reward and motivation, social attention and action observation, and social perception. In this study, researchers used a neuroimaging technique called functional magnetic resonance imaging (fMRI), a technique that measures blood oxygen level-dependent (BOLD) response to behavior. The BOLD response is measured on the premise that blood oxygen levels are higher in active parts of the brain. The researchers measured the BOLD response to identify brain areas that are active while observing a filmed presentation of social situations to predict how children with ASD would respond to behavioral intervention. The average age of the children with ASD was 6 years old.

The behavioral intervention used in this study was a 16-week pivotal response treatment (PRT)—a naturalistic, behavior-based approach designed to increase social motivation. The treatment consisted of 7 hours of treatment per week, 5 of which involved direct work with the child and 2 of which consisted of parent training. Tasks involved play-based activities between parent and child to reinforce social behaviors such as social initiation and responsiveness to social cues.

The researchers used a battery of clinical assessments and an fMRI task to determine a baseline before the intervention and any change after the treatment. The battery of clinical assessments included the parent-reported Social Responsiveness Scale (SRS), the Clinical Evaluation of Language Fundamentals (CELF), and the clinician-administered Vineland-II, which is a scale that assesses adaptive behavior. During the fMRI scan, the children observed a series of filmed motion displays. These displays consisted of a “point-light stimulus,” which is a recording of an adult male actor with lights attached to his major joints, filmed in the dark performing common movements. This motion display paradigm has been well-established in research to engage the brain regions involved in social motivation.

The results of this study show that PRT reduced the severity of ASD symptoms, as measured by the parent-reported SRS. Importantly, the researchers identified key brain areas that showed activity correlated with improvement in ASD symptoms in response to PRT. The researchers also conducted an analysis to identify patterns across different brain areas that could predict response to the PRT. The patterns of brain activity they found were precise enough to predict response to PRT for the children with ASD.

The key brain areas involved in social information processing were the right posterior superior temporal sulcus (involved in perception of eye gaze, emotion, and biological motion), the fusiform gyrus (face perception), and the right superior parietal lobule (distribution of spatial attention). The brain areas involved in social motivation were the orbital frontal cortex (emotion and memory), putamen (social learning), and ventral striatum (part of the brain’s reward system).

These results are important because they suggest that clinicians could potentially pre-screen children with ASD to predict whether a treatment such as PRT would be effective in reducing ASD symptoms before treatment occurs. This would allow for more efficient intervention during the critical time window in early childhood to reduce symptoms related to ASD. Moreover, the results provide a roadmap forward to help researchers develop novel ways to help children respond to evidence-based behavioral interventions who otherwise would not respond.

Question 4

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