Cortical Morphometry in Autism Spectrum Disorder

People diagnosed with Autism Spectrum Disorder (ASD) can have lifelong difficulties with language, social interaction and repetitive behaviours. Studies have shown differences in brain anatomy between people with ASD and typically developing people. Improved understanding of how abnormal brain anatomy develops in ASD, and why it differs amongst people with ASD could advance how we diagnose and treat these increasingly recognised conditions.

One of the most important parts of the brain to show differences in ASD is the cerebral cortex, a highly folded structure which covers the brain and processes information during complex human behaviours. However we know very little about cortical anatomy in ASD.

Our preliminary work suggests that the cortex grows differently in ASD and shows most abnormalities in areas important for social behaviour and language. We now want to better understand cortical anatomy in ASD and how it relates to age, symptoms and genetic make-up.

We will applying a set of new techniques for measuring the cortex from brain scans in a large group of 200 men aged between 18 and 55 - half with ASD and half who are developing normally. It is hoped that this would then lead to future studies in children.

Autism Spectrum Disorder (ASD) is an increasingly recognised lifespan-persistent neurodevelopmental disorder. It is characterised by disturbances of communication, social reciprocity and a range of repetitive behaviours. There is extensive evidence of abnormal brain structure and function in ASD. The cerebral cortex appears to be particularly affected. However, to date the study of cortical anatomy in ASD has largely been limited to the analysis of grey matter volume (GMV) in small and heterogenous samples.
The aim of this study is to better understand the relationship between cortical anatomy and diagnosis, age and clinical profile in ASD. Specific hypotheses to be tested within ASD have been generated in part by my own pilot work and address (i) selectivity of abnormalities in cortical anatomy to regions important in social cognition and executive functioning, (ii) differences in fronto-temporal cortical maturation (iii) variation of cortical anatomy according to symptom severity. I also hope to begin extending my pilot work on gene-brain relationships, and examining connectivity using structural co-variance.
To do this I wish to be trained (in the USA and UK) in the use of novel methods for the analysis of structural magnetic resonance images (sMRI) to measure cortical GMV, thickness (CT), surface area (SA) and gyrification. These techniques will be applied within what would be the largest sample to be so studied to date - a well-characterised group of 100 adult males with ASD and 100 controls aged 18-55 (MRC UK Autism Multicentre Imaging Study). We also hope to extend these techniques to a sample of children with ASD through the National Institute for Health Research.
The results of such work will improve our understanding of which cortical systems show structural abnormalities in ASD and how these develop over time. CT and SA are closely interrelated, but have differing biological determinants. Revealing how these aspects of cortical anatomy interact and relate to abnormalities of GMV in ASD will help to identify underlying neuropathological mechanisms ASD. Such approaches also have translational potential. By starting to inter-relate behaviour, brain anatomy and genotype the heterogeneity of ASD could be parsed and thus improve our understanding of the biological basis of ASD. Finally this project has a capacity building role as it will establish new research methodologies within the UK and build close links with a US centre which has the largest body of developmental sMRI data in the world.