Neural Activity of 16p11.2 CNV Human and Mouse

Although rare in the population, individuals affected by deletions or duplications of DNA material at 16p11.2 chromosomal region (within the region ’11.2’ in the short arm of chromosome 16) are at higher risk of myriad clinical features and neurodevelopmental disorders including intellectual disability, developmental delays, and autism spectrum disorder. Whether inherited or appearing for the first time in the family, this 16p11.2 copy number variation (CNV) seems to impact on brain structure and function that may, in turn, drive the profile and severity of 16p11.2 associated phenotypes. As studies of 16p11.2 CNV brain function are scarce, the aim of this thesis is to investigate EEG activity in (human) 16p11.2 CNV carriers and parallel in-vivo electrophysiological activity in 16p11.2 deletion mouse model. Data-sharing platforms and collaborative efforts made it possible to access datasets of this rare population and analyse it for the purpose of this thesis. The thesis is comprised of three studies: 1) an investigation of visual-evoked neural variability, as measured by variability of intra-participant ERP and spectral power, and signal-to-noise ratio, in 16p11.2 CNV carriers; 2) a study of spontaneous neural activity, as measured by multi-scale entropy and conventional spectral power, in 16p11.2 deletion carriers; and 3) a study of spontaneous neural activity in 16p11.2 deletion mouse model. Neural variability was mostly higher in 16p11.2 deletion carriers relative to typical controls and 16p11.2 duplication carriers. Compared to typical controls, higher entropy was found in 16p11.2 deletion carriers and this was associated with certain psychiatric and behavioural traits, e.g., anxiety problems. The 16p11.2 deletion mice showed no group differences in neural activity compared to wild-type control mice. In conclusion, despite the lack of converging evidence from the mouse model, the collective 16p11.2 CNV human findings indicated that neural activity in 16p11.2 deletion carriers, especially, was altered and related to psychiatric traits found in 16p11.2 deletion carriers.