Autism spectrum disorder (ASD) is an exceedingly heterogeneous disorder with limited empirically validated behavioral and biological interventions. The goal of this pilot investigation is to apply a biologically-based approach to identify predictors of treatment response in children with ASD who are receiving Pivotal Response Treatment (PRT), an evidence-based behavioral intervention. Specifically, we propose to identify neuroimaging biomarkers of treatment response to a PRT program (PRT-P) targeting language deficits in young children with ASD who will be randomized to either PRT-P or to a delayed treatment group (DTG). At the end of the controlled phase, families randomized to the DTG will be invited to participate in a PRT in an open-label trial. PRT-P will consist of 4 months of parent-training sessions to teach parents how to apply PRT in the natural environment. Standardized and video-taped assessments will be conducted at baseline, week 8, and post- treatment and will be rated by an investigator blinded to treatment group. Neuroimaging data will be obtained at baseline and at the end of the trial and will include anatomical MRI, diffusion tensor imaging (DTI), resting state functional magnetic resonance imaging (rs-fMRI), and 1H magnetic resonance spectroscopy. Based on the established evidence and our previous trials, we expect that parents participating in PRT-P will demonstrate evidence of targeted skills at post-treatment and that their children will show significant benefits in language abilities, relative to those in the DTG. We also hypothesize, based on our preliminary data, that baseline neuroimaging measures from the frontal and temporal language areas will predict treatment response to PRT-P. This investigation will be an important step towards identifying potential biosignatures of treatment response, which are critical for young children with ASD, and permit the examination of whether improvements in language abilities are associated with neurobiological changes in the brain. Findings from this pilot study will also be instrumental in designing larger trials that will help in the dissemination of parent-delivered early interventions to children with ASD and will lay the foundation for a research program focused on the discovery of neuroimaging biomarkers of treatment response.
The goal of this pilot investigation is to use non-invasive neuroimaging measures to identify predictors of treatment response in children with ASD who are receiving Pivotal Response Treatment, an evidence-based behavioral intervention, to target language deficits. Anatomical MRI, diffusion tensor imaging, 1H magnetic resonance spectroscopy, and resting state functional MRI data will be obtained at baseline and at the end of the trial. Improvement in language abilities with treatment will be examined in relationship to baseline neuroimaging measures and to changes in neuroimaging measures following treatment.
