The behavioural phenotype of neurofibromatosis type 1: a cognitive and neuroimaging perspective

Abstract

This thesis provides insight into the behavioural phenotype of NF1 by assimilating data on the cognitive, structural, and functional brain correlates of behavioural dysfunction in NF1, specifically attention deficit hyperactivity disorder (ADHD) and social dysfunction. Collectively, thesis results constitute a relevant finding to understanding the social profile of adults with NF1, providing the first quantitative evidence of dysfunction in pro-social behaviours and higher-level social cognition. Magnetic resonance imaging (MRI) data suggest a neuroanatomical basis for this deficit; grey matter volumetric reduction in the right superior temporal gyrus. The studies in this thesis also provide data on the cognitive and neural correlates of ADHD symptomatology in children with NF1. Our results suggest that deficits in response inhibition, working memory and attention are not unique to those with NF1 and comorbid ADHD, but are central and core characteristics of the NF1 cognitive phenotype. Functional MRI findings lend support to the view that dysfunction of the pre-supplementary motor area may be an important contributor to deficient response inhibition in NF1. Assimilating our findings on the structural and functional correlates of behavioural dysfunction with data from preclinical and basic science literature will further knowledge in these areas and guide future clinical trials.