The Autism Biomarkers Consortium for Clinical Trials: Initial Evaluation of a Battery of Candidate EEG Biomarkers

Abstract

Objective: Numerous candidate EEG biomarkers have been put forward for use in clinical research on autism spectrum disorder (ASD), but biomarker development has been hindered by limited attention to the psychometric properties of derived variables, inconsistent results across small studies, and variable methodology. The authors evaluated the basic psychometric properties of a battery of EEG assays for their potential suitability as biomarkers in clinical trials.

Methods: This was a large, multisite, naturalistic study in 6- to 11-year-old children who either had an ASD diagnosis (N=280) or were typically developing (N=119). The authors evaluated an EEG battery composed of well-studied assays of resting-state activity, face perception (faces task), biological motion perception, and visual evoked potentials (VEPs). Biomarker psychometrics were evaluated in terms of acquisition rates, construct performance, and 6-week stability. Preliminary evaluation of use was explored through group discrimination and phenotypic correlations.

Results: Three assays (resting state, faces task, and VEP) show promise in terms of acquisition rates and construct performance. Six-week stability values in the ASD group were moderate (intraclass correlations ≥0.66) for the faces task latency of the P1 and N170, the VEP amplitude of N1 and P1, and resting alpha power. Group discrimination and phenotype correlations were primarily observed for the faces task P1 and N170.

Conclusions: In the context of a large-scale, rigorous evaluation of candidate EEG biomarkers for use in ASD clinical trials, neural response to faces emerged as a promising biomarker for continued evaluation. Resting-state activity and VEP yielded mixed results. The study's biological motion perception assay failed to display construct performance. The results provide information about EEG biomarker performance that is relevant for the next stage of biomarker development efforts focused on context of use.

Keywords: Autism Spectrum Disorder; Biological Markers; Neurodevelopmental Disorders; Neuroscience.

FIGURE 1.. EEG resting state, faces task, visual evoked potential, and biological motion recognition task for the ASD and the typically developing groups^a

^a Graphs in the first row are for EEG resting state, in the second row for the faces task, in the third row for visual evoked potentials, and in the fourth row for the biological motion recognition task. Panel A shows group-averaged power by frequency spectrum and slope at time 1; panel B is a histogram of slope values at time 1; panel C shows the 6-week stability of the slope from time 1 to time 2 (T1 to T2); panel D shows the upright faces (solid line) and upright houses (dotted line) group-averaged event-related potential (ERP) waveform at T1; panel E is a histogram of N170 latency to the upright faces at T1; panel F shows the 6-week stability of N170 latency upright faces values from T1 to T2; panel G shows the checkerboard VEP group-averaged ERP waveform at T1; panel H is a histogram of the P100 amplitude to checkerboards at T1; panel I shows the 6-week stability of the P100 amplitude to checkerboards from T1 to T2; panel J shows the biological (solid line) and scrambled motion (dotted line) group-averaged ERP waveform at T1; panel K is a histogram of the P300 amplitude biological motion specificity (BMS) effect at T1; and panel L shows the 6-week stability of the P300 amplitude BMS response from T1 to T2. Shading in panels A, D, G, and J indicates standard error of the mean. ASD=autism spectrum disorder group; BMS=biological motion specificity effect; TD=typically developing group.