Age-Related Changes in Auditory Event-Related Potentials Differ Between Typically Developing Toddlers and Those with Autism Spectrum Disorder.

Background:  Unusual sensory-related behaviors, particularly in response to sound and touch, are associated with the phenotype of autism spectrum disorder (ASD) and such behaviors are now part of DSM-V criteria. However, little is known about the developmental trajectory of brain responses elicited by sensory stimuli in young children with ASD or how they differ from those in typically developing children.

Objectives: In this study, part of a larger, on-going project to identify autism subphenotypes (The Autism Phenome Project), we sought to identify the relation between chronological age and electrophysiological markers of auditory sensory processing in young typically developing children and those with ASD. Our approach was to examine the electrocortical response amplitude to stimuli of increasing loudness.

Methods:  61-channel event-related potentials (ERPs) were elicited by randomly presented 50, 60, 70, and 80 dB 50-ms complex tones via headphones from 31 typically developing (TD) and 52 children diagnosed with ASD. Diagnostic criteria were based on ADOS, ADI-R, DSM-IV and clinical observation. All children (26 - 63 mos.) had clinically normal hearing. A total of ~1200 stimuli with inter-stimulus intervals of 1-2 s were presented as children passively listened to the stimuli and watched a quiet video of their choice. Gross artifact-free average referenced concatenated epochs from -200 to +600 ms were submitted to Second Order Blind source Identification (SOBI) and signal sources identified as noise (e.g. emg, blinks) were removed. The remaining sources were combined, projected back into electrode space, and averaged by intensity per individual. The global field power (GFP) waveforms were analyzed time-point by time-point separately by intensity using Group (TD vs. ASD) as a between subjects factor and Age as a covariate. Significant time periods of Group by Age interactions were identified using a threshold of at least 15 contiguous time-points with p<=0.05. For each individual at each stimulus intensity level, we computed the average GFP across post-stimulus time windows defined by durations of significant interactions. Pearson correlations of these GFP values and age were performed.

Results: Significant Group by Age interaction time windows were found for 50 dB (70-100 ms), 60 dB (70-95 ms), and 70 dB (285-330ms) stimulus intensities. For all three of these conditions we observed significant correlations of increasing GFP amplitude with age for the TD children (50 dB TD r = 0.49, p<.001; 60 dB TD r = 0.47, p<.001; 70 dB TD r = 0.36, p=.04). No significant correlations with age were found in the ASD group.

Conclusions: These data extend the corpus of results demonstrating differences in auditory responses between TD children and those with ASD to investigation of ages 2-5 years—a period of development which includes marked changes in neuroanatomical maturation, cognitive development and typical acquisition of interpersonal skills. The data suggest that there are brain maturational-dependent processes present in TD children that may be delayed or disturbed in ASD. These results are in line with white matter tract differences that have been shown to differ in maturation between TD and ASD children of the same age range.