EEG Neural Variability Distinguishes 16p11.2 Deletion and Duplication Carriers

Background:

Copy number variations (CNV) at the 16p11.2 chromosomal locus (~600 kb breakpoints 4–5 (BP4-BP5)) are associated with myriad clinical features including intellectual disability, autism spectrum disorder (ASD), epilepsy, and language and motor delays. Importantly, trends of reciprocal phenotypic differences between deletions (DEL) and duplications (DUP) have been consistently observed across multiple traits (e.g., brain volume and structures (Chang et al., 2016; Maillard et al., 2014), BMI (Jacquemont et al., 2011), EEG signals (LeBlanc and Nelson, 2016; Jenkins et al., 2016), etc.), which have been interpreted as indicating gene-dosage effects. However, as 16p11.2 CNVs are rare, there has been only four studies (LeBlanc and Nelson, 2016; Jenkins et al., 2016; Berman et al., 2016; Hudac et al., 2015) that phenotyped the EEG activity of carriers and no study examined reciprocal neural variability patterns.

Objectives:

The aim of this study is to determine whether 16p11.2 DEL and DUP carriers demonstrate a distinct and reciprocal pattern of EEG activity as represented by neural variability and signal-to-noise (SNR) measures.

Methods:

EEG data of the 16p11.2 CNV and typical groups were previously collected as part of the Simons Variation in Individuals Project (Simons VIP Consortium, 2012). Neural variability measures, as estimated by single trial ERP and spectral power analyses in the alpha and beta frequency bands, in addition to SNRs, were analysed in the CNV (n=28) and typical groups (n=11).

Results:

Intra-participant variability in ERP amplitude and absolute alpha power was significantly higher in DEL compared to controls (and compared to DUP for the latter measure). Relative alpha variability was significantly lower in DUP relative to both DEL and controls. SNRs did not differ between the groups. Patterns of EEG activity did not support indications of gene-dosage effects.

Conclusions:

The findings indicate that 16p11.2 CNV groups have a distinctly atypical pattern of EEG activity, as indexed by neural variability measures, that is gene-dosage independent. The overall neural variability patterns were conceptualised as relating to cognitive processing and neural plasticity.