Mu Suppression to Biological Motion Predicts Pivotal Response Treatment Response in Young Children with Autism Spectrum Disorder

Background:   Advances in cognitive neuroscience offer promise for personalized treatment to improve outcomes in individuals with ASD. As a treatment with established clinical efficacy, Pivotal Response Treatment (PRT) is a naturalistic behavioral intervention that uses Applied Behavior Analysis (ABA) principles to target social communication deficits in individuals with Autism Spectrum Disorder (ASD) (Koegel et al., 1987). Work from our group (Ventola et al., 2014) has found significant benefit in pragmatic language, social engagement, and adaptive functioning skills for children with ASD and corresponding brain-based normalization (Ventola et al., 2015). Employing electroencephalography (EEG), this study aims to detect pre-existing functioning in the brain circuitry supporting biological motion that predicts which children benefit most from a 16-week course of PRT. Such predictive power could lead to the establishment of a stratification biomarker to help precisely match patients to treatments. 

Objectives:   We present preliminary findings from an ongoing clinical trial to be completed in the spring of 2016. We investigated the degree to which EEG neurobiomarkers predict treatment response in a sample (N = 7) of children (4-7 years; 3 girls, 4 boys) with ASD (Mean IQ=87.13 SD=20.53) who participated in a 16-week trial of PRT.

Methods:   Treatment included 6 hours per week of individual work with the child plus parent training. Our Primary clinical outcome was the SRS-2 Total Raw Score (parent report). Participants sat for a high-density EEG session (128-channel Hydrocel Geodesic sensor net), before treatment. During EEG recording, participants were presented with well-validated stimuli depicting point light displays of coherent biological or scrambled biological motion. We evaluated the extent of suppression in the EEG alpha frequency band range (8-12 Hz, mu suppression) in response to viewing biological or scrambled biological motion at baseline and how this measurements predicted the change in the SRS score from baseline to the treatment endpoint. We spectrally analyzed EEG measured over the left and right central regions (corresponding to C3 and C4). Following standard procedures for data normalization (natural log) and computation of mu suppression. We  computed difference between biological motion and rest and the difference between scrambled biological motion and rest considered as a ratio (Bernier, Dawson, Webb, & Murias, 2007).

Results:   A 16-week course of PRT resulted in a significant improvement in levels of social impairment as measured via the SRS-2, t(6) =3.520, p=.013. Moreover, considering mu suppression to biological motion at EEG site C3, repeated measures indicated a significant time (pre vs. post SRS) by mu suppression interaction, F(1, 5)=9.29, p=.028. Scatter plots for the association between C3/C4 and SRS change are presented in Figure 1.

Conclusions:   Our preliminary findings suggest functioning in the neural circuitry that supports social perception predicts who will show the most clinical benefit from a 16-week course of PRT.  Effects were similar for both lateralized cortical regions, though stronger on the left. These results lead the way to help develop stratficiation and target engagement biomarkers for ASD clinical trials.