Executive Function Intervention for High School Students With ASD

Behavioral and Neural Outcomes of a New Executive Function Treatment for Transition-age Youth With ASD

The purpose of this project is to test the effectiveness of a novel school-based intervention targeting executive function skills, including flexibility and planning, in college-track, transition-age youth with ASD. Evaluating treatment change through behavior and brain activity provides important information on how the treatment works and who will best benefit from it.

With half of the $3.2 million lifetime per capita cost of autism spectrum disorder (ASD) attributable to care and productivity loss during adult life, the Interagency Autism Coordinating Committee has identified a pressing need to improve adult outcomes. Even in individuals without intellectual disability who make up 2/3 of children with ASD, as few as 9% reach full functional independence as adults. Failure in college is related to weaknesses in executive function (EF), specifically with flexibility and planning. As such, the transition from high school is a period of amplified risk characterized by poor educational and vocational attainment that persists in adulthood. EF problems are pivotal targets for intervention because they are common, linked to independence, and responsive to treatment in younger children. There are three barriers to treatment outcome research in transition-aged youth with ASD: (1) a lack of proven EF treatments for this age, (2) pervasive failure to generalize skills learned in the clinic to real-world settings, and (3) inadequate objective measures of outcome. This proposal tests the effectiveness of Flexible Futures a new phenotype specific, cognitive behavioral EF intervention to increase flexibility and planning skills for college-track high school students with ASD. It is novel and innovative because its use of translational methods comprehensively evaluates treatment change at the behavioral, cognitive, and neural level. Cognitive flexibility and planning are impaired in ASD, linked to core ASD symptoms, and embedded in anomalies of brain structure and function. Individuals with ASD fail to activate local cortical regions such as dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) on set-shifting (flexibility) tasks and show global abnormalities in the default mode, salience, and attentional networks associated with EF problems in attending to important information and implementing goal-directed behavior. In typical development, greater segregation between and greater connectivity within these networks is associated with better cognitive and behavioral regulation. Dr. Pugliese aims to determine whether treatment change can be objectively measured in the brain using functional MRI (fMRI). This cutting edge methodology is critical to identifying processes of treatment change at the neural level, consistent with the NIMH Research Domain Criteria framework, and may yield findings that impact the large variety of psychiatric and developmental disorders linked to EF deficits. Specifically, this study aligns with NIMH K23 guidance soliciting proposals for the development of pilot studies of novel treatments eliciting mechanisms of change. AIM 1: Refine the Flexible Futures treatment manual and test acceptability, feasibility, and effectiveness in a school setting. Dr. Pugliese will refine the Flexible Futures manual based on expert opinion and feedback from our in-clinic pilot via an iterative process and run a school-based trial comparing Flexible Futures to social skills treatment. It is hypothesized that intervention acceptability, feasibility, and fidelity will reach an 80% benchmark (H1.1) and students who receive Flexible Futures will show improved EF flexibility and planning abilities in laboratory, school, and home settings post-treatment and at 5-month follow up compared to students who receive treatment as usual (H1.2). AIM 2: Identify neural correlates of treatment change using fMRI. Task-evoked and resting-state activation of prefrontal cortex networks will be assessed pre-/post-intervention. It is hypothesized that post-treatment, students receiving Flexible Futures will display increased (normalized) DLPFC and ACC activation during a well-established set-shifting task compared to those receiving social skills training (H2.1), and that activation will be positively correlated with behavioral/cognitive measures of EF (H2.2). It is also hypothesized that post-treatment, students receiving Flexible Futures will display increased connectivity within, and decreased connectivity across default mode, salience, and attentional networks compared to the control group (H2.3). AIM 3: Identify biomarkers of later EF outcomes at the behavioral, cognitive, and neural level. Baseline data will be combined across participants to provide a comprehensive EF profile in transition-age youth and identify predictors of later EF and global outcomes. It is hypothesized that baseline measures of EF (behavioral/ cognitive); DLPFC/ACC activation; and greater connectivity within and greater segregation between salience, attentional and default mode networks (neural) will all predict EF outcome and adaptive function. (H3.1). Significance: Establishing the first effective school-based EF treatment for high-schoolers will provide critical and generalizable transition-related support, and a model for treatment in other prevalent disorders with known EF deficits (e.g. ADHD, anxiety). This training award will launch me toward Dr. Pugliese's ultimate career goals of 1) developing and implementing innovative interventions personalized for specific cognitive profiles, 2) developing school-based treatments to overcome disparities in access to healthcare; and 3) utilizing treatment studies as vehicles to identify biomarkers and provide insight into neural correlates of treatment change.

Autism Spectrum Disorder, Executive Functioning, Intervention, Flexible, Unstuck, Transition, Behavior, High school, Problem Solving, Self-Control, Coping

Assessor and observers will be blind to the treatment. Classroom observations will be conducted by "partially blind classroom observers." Though the observer will not be told which schools are assigned to which treatment condition, we found that in our last trial occasionally an observer saw treatment materials that suggested which treatment the school had been assigned to. We will make every effort to minimize this, but it may occasionally happen. The pre-post direct child assessments will also be conducted by treatment-blind assessors, as much as possible.

Flexible Futures uses cognitive behavioral therapy (CBT) techniques to target flexibility and planning by teaching core skills through personal goals chosen by students during treatment. Flexible Futures focuses on key functions needed for college success, such as: intrinsic motivation, how to implement skills socially, how thoughts and feelings affect planning and flexibility, self-advocacy skills necessary to promote independence, application of flexibility and organization scripts and strategies in the service of a long-term goal, and management of time and priorities. Guided practice begins with concrete interventionist support, and moves to interventionist cueing, self-cueing, and finally automatic use of the skills without support. Generalization is maximized with school staff as interventionists, parent training, home and classroom extension activities, and role-playing use of strategies in novel situations. Motivation is developed using student choice and natural motivators.

Flexible Futures is a novel and innovative cognitive-behavioral treatment that directly addresses executive function and self-regulation deficits in ASD. Flexible futures targets flexibility and planning through self-regulatory scripts that are consistently modeled and reinforced. Scripts compensate for the inner speech and organization/integration deficits in ASD, and are practiced repeatedly to achieve automaticity. Content focuses on key functions needed for college success, such as: intrinsic motivation, how to implement skills socially, self-advocacy skills application of flexibility and organization scripts and strategies in the service of a long-term goal, and management of time and priorities.

Flexible Futures will be compared to a social skills treatment as usual that capitalizes on current standard of care provided by local school districts.

Change in Behavior Rating Inventory of Executive Function (BRIEF)- Self-Report Form (Gioia, Isquith, Guy & Kenworthy, 2000).

This self-report measure has 55 items with seven clinical scales and three validity scales. It is normed for adolescents between 11 and 18 years of age. Items were developed to capture everyday behaviors associated with EF and tap seven domains: Inhibit, Self-Monitor, shift, Emotional Control, Task Completion, Working Memory, and Plan/Organize. The BRIEF is standardized with normative data expressed as T scores (mean=50; SD=10). Internal consistency is high, with index coefficients in the mid .90s to high .90s, while test-retest stability coefficients for the clinical scales ranged from .67-.79 within the standardization subsample. The individual scales and summary indexes were correlated in various clinical samples with other measures of attentional and behavioral functioning (Behavior Assessment Scales for Children, Child Behavior Checklist, ADHD-RS-IV, Conners 3), providing evidence of convergent and divergent validity. Safety Issue: No

The Challenge Task is an unpublished, un-normed measure designed by the study staff to measure flexibility and planning in a social context with standardized tasks (Anthony & Kenworthy, 2012). It is a 20-minute play interview that challenges children to be flexible and planful in the context of three activities with an examiner. Specific challenges are posed, and the child's flexibility and planning are scored on a 3-point scale for each task. The scale has task-specific behavioral markers to guide. The CT yields average Flexibility and Planning scores (higher scores indicate greater impairment). Reliability observations will be completed with a second coder for 25% of the videotapes. Examiners in a previous trial achieved interrater agreement >90%, and we will maintain that same standard for the current project. Safety Issue: No

Change in Wechsler Abbreviated Scale of Intelligence- Second Edition (WASI-II, Wechsler, 2011), block design subtest

The WASI-II is an estimate of intelligence, comprised of four subtests, which takes 30-45 minutes to administer. It is a well-standardized task with normative data for ages 6-90. Subtests include the Block Design subtest, the Similarities subtest, the Matrix Reasoning subtest, and the Vocabulary subtest. Performance on each subtest is represented as a T score (mean=50; SD=10), with higher scores indicating better performance. Overall IQ is calculated from a composite of all four subtests and is represented as a standard score (mean=100; SD=15). The entire WASI-2 will be completed at the Baseline Evaluation to identify full-scale IQ and verbal age (based on the vocabulary subtest). Subsequently, the Block Design subtest only will be completed at the Post-Treatment and Long-term Follow-up Evaluations. Safety Issue: No

Change in Delis-Kaplan Executive Functioning System (DKEFS; Delis, Kaplan, and Kramer, 2001), Sorting subtest

The DKEFS is a standardized measure of executive functioning skills and in normed for ages eight through adulthood. The Sorting Subtest particularly measures flexibility. The DKEFS will be completed both at the Baseline and, the Post-Intervention Evaluation as measure of outcome. It takes approximately 10 minutes to administer, and although specific data were not available, the measure has been well documented across several neuropsychological studies to have evidence of reliability and validity. Safety Issue: No

TOL-DX measures multiple EFs such as planning, inhibition, and working memory. It requires the subject to work step-by-step to copy a pattern of beads on pegs using the least number of moves possible. The total-moves score will be measured as an omnibus measure of EF. Results are reported as standard scores (M = 100; SD = 15). Safety Issue: No

(ABAS-II; Harrison and Oakland 2003) is a measure of adaptive behavior with national standardization samples representative of the English speaking US population. The informant report adult form of the ABAS-2(Harrison and Oakland 2003) used in the present study was standardized on an age stratified sample and provided information in the areas of Conceptual (including Communication, Functional Academics, Self-Direction), Social (including not only Social but also Leisure), and Practical (including Community Use, Home Living, Health and Safety, Self-Care) Skills, all of which are presented as norm-referenced standard scores (M = 100; SD = 15) and were used as correlates of interest in the present study. Safety Issue: No

The SRS-2 is a 65-item informant report of autistic traits rated on a 4-point Likert Scale (0-3 points). Higher scores indicate more autistic traits; T-scores ≥ 65 (i.e., 1.5 SDs ≥ the population mean of 50) suggest clinically significant autistic traits. The SRS-2 scoring is aligned with DSM-5 criteria for diagnosis of an ASD. The update includes the creation of two higher order indices that correspond to the two symptom domains of ASD: Social Communication and Interaction (SCI) and Restricted Interests and Repetitive Behavior (RRB). Informants provided a single SRS-2 rating for each child in this study. The SRS-2 will be completed at Baseline and Post-Intervention testing. Safety Issue: No

Change in Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2)- Parent Form (Gioia, Isquith, Guy & Kenworthy, 2015).

This parent-report measure contains 63 items with nine clinical scales and three validity scales. It is normed for children ages 5-18. Items were developed to capture everyday behaviors associated with EF and tap nine domains including: Inhibit, Self-Monitor, Shift, Emotional Control, Initiate, Working Memory, Plan/Organize, Task-Monitor, and Organization of Materials. It is a standardized questionnaire with normative data and standardized scores expressed as T scores (mean=50; SD=10). Internal consistency is high, with index coefficients above .90, while test-retest stability coefficients for the clinical scales ranged from .67-.92 within the parent standardization subsample. The individual scales and summary indexes of the BRIEF-2 were correlated in various clinical samples with other measures of attentional and behavioral functioning (BASC, CBCL, ADHD-RS-IV, Conners 3), which collectively provided evidence of convergent and divergent validity. Safety Issue: No

To meet the needs of the current study by addressing the issue of flexibility more specifically, we will modify the BRIEF to include 14 additional unpublished, unnormed "Flexibility" and "Interference" items. These items will assess how much flexibility impacts the child's and family's life. The items will use a 0-3 scale (0-No Interference, 1-Mildly interfering , 2-Moderately Interfering, 3- Severely Interfering) and will ask about behavior observed during the past two weeks (example: "How much do difficulties with flexibility interfere with or disrupt everyday activities (self-care, school, etc.?)") Safety Issue: No

The SKAMP is a teacher rating scale that takes 5 minutes to complete and assesses impairment from classroom behaviors associated with executive function in adolescents. Although our study uses a modified form of the SKAMP for which reliability and validity data are unavailable, previous community-based trials of the SKAMP showed evidence of high internal consistency, with reliabilities of .98 for overall SKAMP scores, .96 for Deportment (Behavior), and .95 for Attention. The SKAMP was found to be strongly correlated to both parent and teacher versions of the Swanson, Nolan, and Pelham-IV (SNAP-IV; r = .93 and .79 for Inattention and Hyperactivity/Impulsivity). Teachers rate the severity of 10 common behaviors on a 4-point scale, including 6 items related to attention and 4 items related to problematic behavior. Safety Issue: No

To further assess functional improvement, at least two 15-minute classroom observations will be conducted by an intervention-blind research assistant (who has achieved reliability on coding criteria) for every study participant. They will occur randomly during the academic school day, but not during Flexible Futures small group sessions or Social Skills training. The following behaviors will be coded for children in this study: Reciprocity, Following Rules, Transitions, Gets Stuck, Negativity/Overwhelm, and Classroom Participation. During the classroom observations, the following behaviors will be coded for the teacher's behavior: Flexibility, Planning/Organizing, Provides Clear Instructions/ Expectations, Actively Uses Visual Support, References Classroom Rules, Maintains Positive Praise: Command/Correction ratio and Uses Reward System. Safety Issue: No

A task-based fMRI procedure will be used to detect pre-to-post treatment change. Participants will classify pairs of stimuli (objects and pictures) on the basis of how well they "go together" and respond with an appropriate button press. The specific task may change based on pilot results but will be similar to what is proposed. Safety Issue: No

Inclusion Criteria: College-track high school students Ages 14-22 Verbal IQ estimate of ≥ 90 on the Wechsler Abbreviated Intelligence Scale-2 Clinical diagnosis of ASD OR school classification of autism confirmed by clinical impressions and the Social Responsiveness Scale-Revised total score ≥ 65. If the research staff feels that clinical impressions indicate a diagnosis, but parent report is below threshold, the Autism Diagnostic Observation Schedule-2 will be completed. Exclusion Criteria: Bipolar disorder, schizophrenia, or major depression that is currently preventing from participation in classroom activities MRI exclusion: contraindication (metal implant or medical device) for MRI

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