Executive Function Intervention for High School Students With ASD
Condition: Autism Spectrum Disorder
MeSH terms: Autism Spectrum Disorder
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Flexible Futures; Current standard of care
Intervention type(s): Behavioral; Other
Intervention description(s): 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.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Autism Spectrum Disorder; Executive Functioning; Intervention; Flexible; Unstuck; Transition; Behavior; High school; Problem Solving; Self-Control; Coping