Cortical Morphometry in Autism Spectrum Disorder
Lead Research Organisation:
King's College London
Department Name: Unlisted
Abstract
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.
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.
Technical Summary
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.
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.
Organisations
- King's College London, United Kingdom (Fellow, Lead Research Organisation)
- National Institutes of Health, United States (Collaboration)
- National Cancer Institute (NCI) (Collaboration)
- Hunter Medical Research Institute (Collaboration)
- Hospital for Sick Children, Toronto (Collaboration)
- Thomas Jefferson University (Collaboration)
- University of California Los Angeles, United States (Collaboration)
People |
ORCID iD |
Armin Raznahan (Principal Investigator / Fellow) |
Publications

Hedrick A
(2012)
Autism risk gene MET variation and cortical thickness in typically developing children and adolescents.
in Autism research : official journal of the International Society for Autism Research

Raznahan A
(2010)
Cortical anatomy in autism spectrum disorder: an in vivo MRI study on the effect of age.
in Cerebral cortex (New York, N.Y. : 1991)

Raznahan A
(2012)
Allelic variation within the putative autism spectrum disorder risk gene homeobox A1 and cerebellar maturation in typically developing children and adolescents.
in Autism research : official journal of the International Society for Autism Research

Raznahan A
(2011)
Common functional polymorphisms of DISC1 and cortical maturation in typically developing children and adolescents.
in Molecular psychiatry


Raznahan A
(2011)
How does your cortex grow?
in The Journal of neuroscience : the official journal of the Society for Neuroscience

Raznahan A
(2010)
Longitudinally mapping the influence of sex and androgen signaling on the dynamics of human cortical maturation in adolescence.
in Proceedings of the National Academy of Sciences of the United States of America

Raznahan A
(2010)
Cortical anatomy in human X monosomy.
in NeuroImage
Description | American College of Neuropsychopharmacology Travel Award/ACNP |
Amount | £1,000 (GBP) |
Organisation | American College of Neuropsychopharmacology |
Sector | Private |
Country | United States |
Start | 12/2010 |
End | 12/2010 |
Description | Fellowship Award for Research Excellence |
Amount | £1,500 (GBP) |
Organisation | National Institutes of Health (NIH) |
Sector | Public |
Country | United States |
Start | 10/2011 |
End | 10/2011 |
Description | Gaskell Gold Medal |
Amount | £1,000 (GBP) |
Organisation | Royal College of Psychiatrists |
Sector | Learned Society |
Country | United Kingdom |
Start | 07/2008 |
End | 07/2008 |
Description | Human Brain Mapping Travel Award/organization for human brain mapping |
Amount | £500 (GBP) |
Organisation | Organization for Human Brain Mapping (OHBM) |
Sector | Learned Society |
Country | Global |
Start | 05/2010 |
End | 05/2010 |
Description | MRS Young Investigator Research Award |
Amount | £1,500 (GBP) |
Organisation | Medical Research Society |
Sector | Learned Society |
Country | United Kingdom |
Start | 03/2011 |
End | 03/2011 |
Title | Mapping synchronous change within the cortical sheet |
Description | Extension of correlational methods to longitudinal anatomical change |
Type Of Material | Data analysis technique |
Year Produced | 2011 |
Provided To Others? | Yes |
Impact | paper using this method currently in press |
Title | Sex Chromosome Aneuploidy Gene Expression |
Description | Beadarray data on people with Sex Chromosome Aneuploidies (10 each of XO, XXX, XXY, XYY, XXYY), and controls (10 XX, 10 XY) |
Type Of Material | Database/Collection of Data/Biological Samples |
Provided To Others? | No |
Impact | Analysis underway |
Description | Developmental Imaging Genetics |
Organisation | National Institutes of Health (NIH) |
Department | National Institute of Mental Health (NIMH) |
Country | United States |
Sector | Public |
PI Contribution | Analytic concepts and execution |
Collaborator Contribution | Statistical, genetics and neuroimaging advice |
Impact | Publications (all with Giedd as co-author) |
Start Year | 2008 |
Description | Gene expression in lymphoblastoid cell-lines from groups with varying sex chromosome aneuploidies |
Organisation | National Cancer Institute (NCI) |
Country | United States |
Sector | Public |
PI Contribution | Study design, co-ordination of collaborations, preparation of materials for transcriptomics, data analysis |
Collaborator Contribution | FISH confirmation of SCA stability through LCL derivationCell lines from XO children |
Impact | Stability of SCA through LCLC derivation established. Genome wide beadarray-based gene expression measured gathered on all 80 participants Preliminary results from comparative gene expression analysis secured. Detailed analysis currently underway. |
Start Year | 2010 |
Description | Gene expression in lymphoblastoid cell-lines from groups with varying sex chromosome aneuploidies |
Organisation | Thomas Jefferson University |
Department | Department of Pediatrics |
Country | United States |
Sector | Academic/University |
PI Contribution | Study design, co-ordination of collaborations, preparation of materials for transcriptomics, data analysis |
Collaborator Contribution | FISH confirmation of SCA stability through LCL derivationCell lines from XO children |
Impact | Stability of SCA through LCLC derivation established. Genome wide beadarray-based gene expression measured gathered on all 80 participants Preliminary results from comparative gene expression analysis secured. Detailed analysis currently underway. |
Start Year | 2010 |
Description | Neuroimaging Study of Childhood Turner Syndrome |
Organisation | Thomas Jefferson University |
Department | Department of Pediatrics |
Country | United States |
Sector | Academic/University |
PI Contribution | Application of Surface Based Morphometric methods for cortical analysis |
Collaborator Contribution | Provision of scans which would otherwise not be available |
Impact | Work still underway |
Start Year | 2009 |
Description | Neuroimaging Study of Velocardiofacial Syndrome |
Organisation | Hunter Medical Research Institute |
Country | Australia |
Sector | Academic/University |
PI Contribution | Methods for surface-based morphometry of the cortical sheet |
Impact | Work still underway |
Start Year | 2009 |
Description | Neuroimaging and Histological Study of Mouse Models for Sexually Dimorphic Genetic and Hormonal Determinants of Brain Development |
Organisation | Hospital for Sick Children, Toronto |
Department | Toronto Center for Phenogenomics (TCP) |
Country | Canada |
Sector | Academic/University |
PI Contribution | Analysis of parallel models in humans Identifying providers of different mouse models |
Collaborator Contribution | Expertise in mouse imagingProvision of Mice |
Impact | Study of XO mice underway (involving further collaboration with Montreal Neuroimaging Institute (histology), Canada and Baylor College of Medicine, Texas, USA (Mouse breeding). Study of mouse model for varying androgen receptor function underway (involving further collaboration with Ann Arbour (provision of mice) Study of XXY mouse model underway |
Start Year | 2009 |
Description | Neuroimaging and Histological Study of Mouse Models for Sexually Dimorphic Genetic and Hormonal Determinants of Brain Development |
Organisation | University of California, Los Angeles (UCLA) |
Department | School of Medicine UCLA |
Country | United States |
Sector | Academic/University |
PI Contribution | Analysis of parallel models in humans Identifying providers of different mouse models |
Collaborator Contribution | Expertise in mouse imagingProvision of Mice |
Impact | Study of XO mice underway (involving further collaboration with Montreal Neuroimaging Institute (histology), Canada and Baylor College of Medicine, Texas, USA (Mouse breeding). Study of mouse model for varying androgen receptor function underway (involving further collaboration with Ann Arbour (provision of mice) Study of XXY mouse model underway |
Start Year | 2009 |
Description | Neuroimaging of Adolescents with Primary Ovarian Insufficiency |
Organisation | National Institutes of Health (NIH) |
Department | National Institute of Child Health (NICH) |
Country | United States |
Sector | Hospitals |
PI Contribution | Neuroimaging expertise |
Collaborator Contribution | Access to rare population |
Impact | Protocol passed through IRB and now in final stages of approval |
Start Year | 2011 |
Description | Shape analysis of sub-cortical structured from MRI |
Organisation | Hospital for Sick Children, Toronto |
Department | MICe Toronto |
Country | Canada |
Sector | Hospitals |
PI Contribution | provision of imaging data, execution of analysis, writing up of results |
Collaborator Contribution | provision of methods for data analysis |
Impact | First methods paper under review Analysis for first developmental paper about to begin |
Start Year | 2011 |
Description | Structural Neuroimaging Study of Young Children with Autism |
Organisation | National Institutes of Health (NIH) |
Department | National Institute of Mental Health (NIMH) |
Country | United States |
Sector | Public |
PI Contribution | analysis of data, interpretation of findings, writing-up |
Collaborator Contribution | Intellectual, provision of data |
Impact | paper under review, analysis underway for subsequent papers |
Start Year | 2010 |
Description | Article in Wall Street Journal |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Primary Audience | Public/other audiences |
Results and Impact | Article published about our work in the WSJ. We worked closely with the journalist. Debate around relevance of our findings for policy in Single Sex Education featured in the journal Science |
Year(s) Of Engagement Activity | 2011 |