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Neural Predictors and Neural Pathway of Response to Pivotal Response Treatment in Young Children with Autism
Objectives: To develop pretreatment neurobiological markers that can predict the response to an evidence-based behavioral treatment—Pivotal Response Treatment (PRT)—in young children with autism, and to examine the neural mechanism underlying treatment effects.
Methods: In a sample (N=20; 7 girls, 13 boys) of young (M age=5.90 years, SD=1.07), cognitively-able (M FSIQ=103.45, SD=17.03) children with ASD, who participated in a 16-week trial of PRT, we measured the change in autism symptom severity by modeling the delta change scores (that is, post minus pre) of the parent-report Social Responsiveness Scale (SRS) total raw scores, while our study participants viewed neuroimaging stimuli depicting point light displays of coherent biological (BIO) or scrambled (SCRAM) motion in a 3T scanner within 1 week before and after PRT. fMRI analyses were conducted with mixed-effects modeling and the results were thresholded at Z>2.33 (voxel) and p<.05 (cluster), while gender was controlled for as a covariate of no interest.
Results: First, with respect to neural predictors, we found that greater reduction in autism symptom severity from pretreatment to post-treatment was linearly associated with greater pretreatment levels of activity in response to biological vs. scrambled motion in the neural circuits that support social information processing (superior temporal sulcus, fusiform gyrus, amygdala, inferior parietal cortex, and superior parietal lobule) and social motivation/reward (orbitofrontal cortex, insula, putamen, pallidum, and ventral striatum) (Figure 1A). The predictive value of our findings for individual children with ASD was supported by a multivariate pattern analysis with cross validation. Second, with respect to neural pathways, we found that greater reduction in autism symptom severity was linearly associated with increase in activity in response to biological vs. scrambled motion in the action observation network (inferior parietal lobule, parietal operculum cortex, supplementary and pre-supplementary cortices located on the medial surface) (Figure 1B).
Conclusions: Predicting who will respond to a particular treatment for ASD and advancing the knowledge of neural pathways of treatment outcomes, the current findings provide key neural bases of behavioral response to treatment in young children with ASD. The implications of the findings are far reaching and should greatly accelerate progress toward more precise and effective treatments for core deficits in ASD.
See more of: Interventions - Non-pharmacologic - Preschool