Neural Mechanisms and Biomarkers of Response to Pivotal Response Treatment

Background: Pivotal Response Treatment is an empirically supported behavioral treatment for ASD that improves social communication skills. Research validating PRT has relied on overt behavioral measures as outcome data, which demonstrate improvements in targeted skills but provide minimal insight into underlying mechanisms of change. Functional magnetic resonance imaging (fMRI) provides us with the opportunity to identify the neural mechanisms underlying the behavioral improvements resulting from PRT.

Our research team has used fMRI to characterize the fundamental components of the neural circuitry supporting social perception in the typically and atypically developing human brain. The social stimuli we utilized, comprised of point light displays of biological motion, have been effectively used to identify brain (Kaiser et al., 2010) and behavioral (Klin et al., 2009) signatures of disruptions in social motivation.

Objectives: This is the first study to demonstrate the clinical efficacy of a short-duration, PRT program versus a waitlist control condition. The outcome measures include standardized assessments, so we are able to demonstrate improvement in specific behaviors and collateral improvements in adaptive functioning and broad-based social communication skills (e.g., social cognition). Additionally, we are able to identify neural-systems-level mechanisms by which PRT improves social communication using a well-tested biological motion neuroimaging paradigm.

Methods: Twelve children, aged 4-6 years, with ASD received 8 hours per week of PRT for 4 months. Six of these children were also first included in a waitlist control condition. Clinical outcome was assessed using the SRS, ADOS, Vineland-II, and clinical observation. Participants completed an fMRI before and after treatment. The children in the waitlist control condition completed an additional fMRI four months prior to treatment. The paradigm was a passive viewing task (328 secs) of point light displays, consisting of 6 biological motion and 6 scrambled motion blocks, presented in an alternating-block design.

Results: The participating children exhibited significant behavioral improvement per clinician assessment and parent report (e.g., on the Vineland-II, improvements in receptive communication, daily living, play, and coping skills were significant at p < .05; SRS Total raw score decreased (improved) by an average of 22.3 with a standard error of 7.8). In addition, the children showed increased activation to social stimuli in brain regions underpinning social function, specifically the left ventrolateral prefrontal cortex (vlPFC), left dorsolateral prefrontal cortex (dlPFC), ventromedial prefrontal cortex (vmPFC), right posterior superior temporal sulcus (STS), and right fusiform gyrus (FFG) (beta difference > .5, k= 40).

Conclusions: The current research introduces an innovative approach for studying response to an empirically supported behavioral treatment by integrating behavioral and neural systems level results. PRT results in significant gains in social communication and adaptive skills even within the context of a short-duration program, which can dramatically increase access to care. Furthermore, neural systems supporting social perception are malleable in children with ASD. The children demonstrated increased activation in key brain regions involved in social processing after conclusion of the treatment program. Further understanding of neural systems level mechanisms will inform predictions of response to treatment and refine interventions toward the goal of personalized care.