Exploring asymmetries from genes, to brains, to minds: a multimodal neuroimaging approach to the putative role of the NODAL signalling pathway in neurocognitive disorders via atypical cerebral lateralisation

Abstract

This thesis investigates the relationship between functional and structural hemispheric asymmetries, by analysing brain anatomy, neurophysiology, neurocognitive and behavioural quantitative laterality measures, in a dyslexia family-based study. The main hypothesis developed and tested in the thesis is that atypical functional and structural hemispheric asymmetries might be the extended endophenotype of a disruption of the NODAL signalling pathway, at the level of the PCSK6 gene, becoming clinically visible during brain development as neurocognitive disorders. In this context, the putative association of PCSK6 rs11855415 genetic variant with developmental dyslexia is used as genotype-phenotype association model, according to which the PCSK6 rs11855415-related structural and functional hemispheric asymmetries are studied as its extended endophenotype, and investigated via a multimodal integrated neuroimaging approach. Within this multidimensional study, different levels of data were acquired from each participant, including: DNA sampling for genotyping, magnetic resonance imaging scans of the brain, magnetoencephalography assessment of receptive language, neurocognitive and handedness testing. By deriving and integrating quantitative measures of grey matter asymmetries, hemispheric language lateralisation and handedness dominance in children with developmental dyslexia and their siblings or twins, this thesis builds a prototypical model of the postulated extended endophenotype of functional and structural hemispheric asymmetries related to PCSK6 rs11855415 genetic variant.

Date of Award	2020
Original language	English
Supervisor	Joel Talcott (Supervisor) & Caroline Witton (Supervisor)