Atypical neural variability in carriers of 16p11.2 copy number variants

Autism Res. 2019 Sep;12(9):1322-1333. doi: 10.1002/aur.2166. Epub 2019 Jul 1.


Copy number variations (CNVs) at the 16p11.2 chromosomal region are associated with myriad clinical features including intellectual disability and autism spectrum disorder. The aim of this study is to determine whether 16p11.2 deletion (DEL) and duplication (DUP) carriers demonstrate a distinct and reciprocal pattern of electroencephalography (EEG) activity as represented by neural variability measures. EEG data were previously collected as part of the Simons Variation in Individuals Project. Variability measures, as estimated by single-trial ERP and spectral power analyses in the alpha and beta frequency bands, in addition to signal-to-noise ratios (SNRs), were analyzed in DEL (n = 20), DUP (n = 8), and typical (n = 11) groups. We also analyzed mean visual evoked potentials and spectral power (alpha and beta power) to facilitate comparisons with other studies of associated disorders and CNVs. From measures of single-trial variability, we found higher intraparticipant variability in P1 amplitude and timecourse amplitude in DEL compared to controls. Compared to DUP, DEL showed higher variability in absolute alpha and absolute beta power but lower variability in P1 latency. SNRs did not differ between the groups. From measures of amplitude, latency, and spectral power, DUP showed lower relative alpha power compared to controls. Although it is yet unclear whether 16p11.2 CNV dosage impacts neural activity in an opposing manner, findings suggest that 16p11.2 DEL impacts the level of variability of neural responses. Higher neural variability may play a role in a range of cognitive processes in 16p11.2 CNV carriers. Autism Res 2019, 12: 1322-1333. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: The study analyzed the consistency of patterns of brain waves and rhythms in those affected with a loss or gain of DNA material in the 16p11.2 region. Compared with typical individuals, 16p11.2 deletion carriers showed greater inconsistency in the way the brain responds to the same visual event. This high inconsistency in brain activity may play a role in some core symptoms in 16p11.2 copy number variation carriers.

Keywords: alpha rhythm; cognitive neuroscience; copy number variation/copy number variants; electroencephalography; event-related potentials; gene-dosage effect; genetic/genomic syndromes.

MeSH terms

  • Adolescent
  • Adult
  • Autism Spectrum Disorder / genetics*
  • Autism Spectrum Disorder / physiopathology*
  • Brain / physiopathology*
  • Child
  • Child, Preschool
  • Chromosome Deletion*
  • Chromosome Duplication / genetics*
  • Chromosome Duplication / physiology
  • Chromosomes, Human, Pair 16 / genetics*
  • DNA Copy Number Variations / genetics*
  • DNA Copy Number Variations / physiology
  • Electroencephalography / methods
  • Evoked Potentials, Visual
  • Female
  • Humans
  • Infant
  • Male
  • Young Adult