Alpha Waves as a Neuromarker of Autism Spectrum Disorder: The Challenge of Reproducibility and Heterogeneity.

There is no consensus in the literature concerning the presence of abnormal alpha wave profiles in patients with autism spectrum disorder (ASD). This may be due to phenotypic heterogeneity among patients as well as the limited sample sizes utilized. Here we present our results of alpha wave profile analysis based on a sample larger than most of those in the field, performed using a robust processing pipeline. We compared the alpha waves profiles at rest in children with ASD to those of age-, sex-, and IQ-matched control individuals. We used linear regression and non-parametric normative models using age as covariate forparsing the clinical heterogeneity. We explored the correlation between EEG profiles and the patient's brain volumes, obtained from structural MRI. We automatized the detection of the alpha peak and visually quality controled our MRI measurements. We assessed the robustness of our results by running the EEG preprocessing with two different versions of Matlab as well as Python. A simple linear regression between peak power or frequency of the alpha waves and the status or age of the participants did not allow to identify any statistically significant relationship. The non-parametric normative model (which took account the non-linear effect of age on the alpha profiles) suggested that participants with ASD displayed more variability than control participants for both frequency and amplitude of the alpha peak ( < 0.05). Independent of the status of the individual, we also observed weak associations (uncorrected < 0.05) between the alpha frequency, and the volumes of several cortical and subcortical structures (in particular the striatum), but which did not survive correction for multiple testing and changed between analysis pelines. Our study did not find evidence for abnormal alpha wave profiles in ASD. We propose, however, an analysis pipeline to perform standardized and automatized EEG analyses on large cohorts. These should help the community to address the challenge of clinical heterogeneity of ASD and to tackle the problems of reproducibility.