Intervention-Induced Plasticity of Flexibility and Learning Mechanisms in ASD

Study Overview
=================
Brief Summary
-----------------
This project explores the association between learning and cognitive flexibility by testing whether a cognitive behavioral intervention designed to improve flexibility in ASD changes learning and associated neural activation using model-based functional magnetic resonance imaging (m-fMRI). The study proposes that variability in learning mechanisms is associated with behavioral flexibility and explains differences in adaptive and treatment outcomes. The study employs a longitudinal case-controlled design in 60 14-18 year old youth with ASD at 3 time-points 8 months apart, each including m-fMRI during learning and behavioral measurement of executive and adaptive function. Aim 1 tests the hypothesis that individual variation in learning biases and their neural correlates predicts behavioral flexibility and is stable over time. Aim 2 tests plasticity of learning mechanisms induced by a cognitive-behavioral intervention for flexibility. Aim 3 tests hypothesis about intervention-induced plasticity of neural functional connectivity.

Official Title
-----------------
Intervention-Induced Plasticity of Flexibility and Learning Mechanisms in ASD

Conditions
-----------------
Executive Dysfunction, Autism Spectrum Disorder, Adolescent Behavior

Intervention / Treatment
-----------------
* Behavioral: Executive function group therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 14-18 years of age inclusive Full scale IQ > 80 on a standardized IQ test, either confirmed through educational testing within the last two years or confirmed by the Wechsler Abbreviated Scale of Intelligence (WASI-2) administered by research personnel. If current IQ testing (FSIQ) is not interpretable based on discrepancies between verbal and perceptual skills, we will use the best available verbal IQ estimate. Broad ASD diagnosis according to Diagnostic Statistical Manual, fifth edition (DSM-5) criteria established by parent report of prior clinical diagnosis and confirmed by meeting cutoff criteria on the Social Communication Questionnaire (i.e., raw score > 11) or the Autism Diagnostic Observation Schedule-2 (ADOS-2), Module 4 (total score ≥7). Intact or corrected hearing and vision. Parents/guardians speak and read English with sufficient fluency for completion of consent forms and informant questionnaires; youth participants will use/understand English as a primary or secondary language with sufficient fluency to engage effectively in executive function group therapy conducted in English, and for valid administration of neuropsychological and behavioral measures. Exclusion Criteria: Presence of a known medical condition in the participant that would interfere with his/her ability to participate in the study. To preserve the integrity of the neuroimaging data, participants will be excluded if they have a history of neurological disorder, such as an established epilepsy diagnosis, significant brain trauma, hydrocephalus, central nervous system infection, or stroke. Contraindications for MRI such as metal implants, dental braces, pregnancy (determined by parent or self-report).

Ages Eligible for Study
-----------------
Minimum Age: 14 Years
Maximum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Executive function group therapy<br> | Behavioral: Executive function group therapy<br>* This executive function group therapy curriculum for adolescents uses cognitive behavioral therapy techniques, and focuses on key functions needed for adult success, such as: self-advocacy, flexibility, time management, motivation, goal setting, developing plans, monitoring progress. Guided practice begins with concrete interventionist support and moves to interventionist cueing, self-cueing, and finally automatic use of the skills without support.<br>* Other names: Proprietary name: Unstuck & On Target (UOT:HS);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Executive Function Challenge Task (EFCT) Scores | The EFCT is an objective and ecologically valid task developed by our research team to assess flexibility and planning skills in a social context conducted by a trained research staff member masked to treatment condition. The EFCT uses a standardized, semi-structured protocol which does not provide explicit rules for completing the tasks to mimic the implicit, unspoken, unstructured expectations in everyday life. The EFCT consists of challenges across several activities and responses are scored on a 3-point scale for each task. The scale (0-good, 1-intermediate, 2-poor performance) has task-specific behavioral markers to guide scoring. | 8-12 months before intervention, at start of intervention, 8-12 months after intervention begins | 
| Change in Neural Response During Prototype Learning Task Outcomes | The Prototype Task measures learning of abstract representations in the visual domain. The task requires classification into two categories of visual exemplars characterized by a number of features (e.g., cartoon fish with features such as a particular eye shape, fins, body shape etc.) for training with feedback. Following training, generalization of learned information is tested on exemplars that are similar to training items but have never been presented before. Participants perform the generalization phase in an MRI scanner for measurement of brain activation. Learning of abstract visual representation (e.g., prototype learning) on this task is indicated by engagement of medial prefrontal cortex (mPFC) | 8-12 months before intervention, at start of intervention, 8-12 months after intervention begins | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Adaptive Behavior Assessment System, Third Edition (ABAS-3) scores | Adaptive behavior will be measured via parent-report on the Adaptive Behavior Assessment System, Third Edition (ABAS-3). The ABAS-3 is a well-validated parent report measure that assesses practical, everyday skills needed to effectively and independently take care of oneself and interact with others across the lifespan. | 8-12 months before intervention, at start of intervention, 8-12 months after intervention begins | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Autism Spectrum Disorder, Executive Function, Intervention, MRI Scanning, Neuroimaging, Learning Mechanisms