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.
