Brain anatomy in autism; a multi-centre study

Lead Research Organisation: King's College London
Department Name: Unlisted

Abstract

In a recent review of research in ASD, the MRC called for more involvement of people with ASD and their ?carers?. Representatives of these groups helped in the design of this study, and our dissemination strategies. They will also be part of the committee that monitors our progress.

The National Autistic Society gave ethical approval to the preliminary work that forms the basis of our proposal. All our research centres have representatives of people with ASD and carers on our project steering boards, and they formulated two key questions that this study will address. First, ?is my brain different from other peoples??. Second, ?if so is that related to some of the things I do??.

Our study Steering Committee (SSC) will include a lay person from the National Autistic Society representing people with ASD.

Also we will produce educational materials, in collaboration with the National Autistic Society, which wil be aimed at health care teams (e.g. in primary care) and the lay public. Specific educational outputs will include written teaching packs and CD roms. These will also be available on our website ? with links to relevant sites. Also, we will design, in collaboration with National Autistic Society, a user-friendly web-based interface that will provide updates on our work, and disseminate findings from other studies. This will be written in lay language. Our findings will also be disseminated nationally by means of workshops and seminars aimed at the lay public, people with ASD, carers, and health professionals.

Technical Summary

The brain basis of autistic spectrum disorder (ASD; including autism and Asperger syndrome) is unknown. The MRC recently called for more research on the neurobiology of ASD, multidisciplinary collaboration, and data sharing between centres. Currently however there is no collaborative UK neuroimaging research program on ASD.

Therefore we propose a two stage development to establish a multidisciplinary neuroimaging research network. During Stage 1 we will launch the network, and carry out technical preparatory work to enable a subsequent multi-centre study (Stage 2) on the neurobiology of ASD. Stage 2 will only be initiated if Stage 1 is successful. In Stage 2, we wish to examine differences in the anatomy and connectivity of brain systems which may underlie ASD using volumetric magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI).

Some people with ASD are reported to have an increase in total brain volume. Also, abnormalities have also been reported in specific brain regions ? particularly in frontal, limbic, basal ganglia, and cerebellar areas (1-8). However, many prior studies have not been replicated, probably because of the clinical heterogeneity and small samples studied. In addition, it is unlikely that abnormalities in a single brain region explain the whole phenotype of ASD. An alternative approach is to investigate the connectivity of brain systems which may underlie abnormal behaviours. Nevertheless very few studies have employed a ?systems? approach, related brain anatomy to symptoms, examined anatomical connectivity, or investigated large homogenous samples.

We propose to study brain anatomy in 100 adults with high functioning ASD (IQ 70) and 100 matched controls using volumetric MRI and DT-MRI. We will test the primary hypothesis that people with ASD have abnormalities in the anatomy and connectivity of ?social brain? systems (frontal and limbic regions), and the basal ganglia and cerebellum. We will also test the subsidiary hypotheses that, within people with ASD, abnormalities in the anatomy and connectivity of specific neural systems are differentially linked to symptoms (e.g. deficits in social behaviour relate to medial frontal and limbic abnormalities; whereas deficits in flexible behaviour are linked to dorsolateral prefrontal cortex, basal ganglia, and cerebellum).

This proposal will establish a multidisciplinary research network, and provide a platform for defining risk factors and mechanisms. If successful we plan future work to examine how the neural abnormalities arise and change across the lifespan; and the effects of genetic, neurochemical, and environmental factors on this process.

Publications

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Asherson P (2010) Is ADHD a valid diagnosis in adults? Yes. in BMJ (Clinical research ed.)

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Asherson P (2012) Under diagnosis of adult ADHD: cultural influences and societal burden. in Journal of attention disorders

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Balardin JB (2015) Relationship Between Surface-Based Brain Morphometric Measures and Intelligence in Autism Spectrum Disorders: Influence of History of Language Delay. in Autism research : official journal of the International Society for Autism Research

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Beacher F (2009) Alzheimer's disease and Down's syndrome: an in vivo MRI study. in Psychological medicine

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Blasi A (2015) Atypical processing of voice sounds in infants at risk for autism spectrum disorder. in Cortex; a journal devoted to the study of the nervous system and behavior

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Bloemen OJ (2010) White matter integrity in Asperger syndrome: a preliminary diffusion tensor magnetic resonance imaging study in adults. in Autism research : official journal of the International Society for Autism Research

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Bolea B (2012) ADHD matures: time for practitioners to do the same? in Journal of psychopharmacology (Oxford, England)

 
Description citaion for using MRI to help diagnose autism
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in systematic reviews
Impact first evidence in the world that sMRI may be a useful tool help help diagnose autism (please note that this is when used in addtion to, and not instead of, clinical interview).
 
Description Autism Speaks funding (Genetics in Autism Spectrum Disorder)
Amount £80,000 (GBP)
Organisation Autistica 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2009 
End 03/2011
 
Description Innovative Medicines Initiative
Amount € 117,000,000 (EUR)
Organisation European Union 
Sector Public
Country European Union (EU)
Start 04/2018 
End 04/2023
 
Description Project Grant - How do white matter tracts develop in the brain between age 6 months and 3 years and how does this relate to early motor, language and social development? Imaging Myelin in Typical Development
Amount £29,600 (GBP)
Organisation Academy of Medical Sciences (AMS) 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2010 
End 06/2012
 
Description Project Grant - Imaging of White Matter and Myelination in normal and autistic neurodevelopment
Amount £1,245,215 (GBP)
Funding ID G0800298 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 09/2008 
End 08/2013
 
Description Wellcome Trust Project Grant (Glutamate and GABA in adults with autism; an in vivo study using magnetic resonance spectroscopy)
Amount £354,175 (GBP)
Funding ID 091300 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2011 
End 12/2013
 
Description european commision
Amount £29,000,000 (GBP)
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 04/2012 
End 04/2017
 
Description training fellowship to Dr S Deoni/The Wellcome Trust
Amount £340,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 05/2008 
End 05/2013
 
Description training fellowship to Dr S Deoni/The Wellcome Trust
Amount £1,100,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 05/2008 
End 05/2013
 
Title Neuroanatomy Database for ASD 
Description This database contains structural brain scans and Diffusion Tensor Imaging scans of 100 healthy controls and 100 individuals with Autism Spectrum Condition (ASD). In addition, we have diagnostic measures as well as behavioural measures related to ASD. 
Type Of Material Database/Collection of Data/Biological Samples 
Provided To Others? No  
Impact This database will help us to examine brain anatomy and connectivity in ASD. 
 
Title Quantitative Imaging 
Description This technique allowed us to combine Magnetic Resonance Imaging scans across multiple centers. 
Type Of Material Data analysis technique 
Year Produced 2006 
Provided To Others? Yes  
Impact This technique will have a strong impact on the way MRI images are acquired and will allow the collection of very large samples at multiple neuroimaging sites. 
 
Title Support Vector Machine on Neuroatatomical MRI scans 
Description This technique allows us to establish the diagnostic (i.e. predictive) value of neuroanatomical MRI scans for ASD. 
Type Of Material Data analysis technique 
Provided To Others? No  
Impact The technique offers a large translational value, which may be used to guide the conventional diagnosis of ASD. 
 
Description EU AIMS 
Organisation European Commission
Department Innovative Medicines Initiative (IMI)
Country European Union (EU) 
Sector Multiple 
PI Contribution This is an EU IMI initiative in autism. We lead this multicentre research network
Collaborator Contribution providinga platform for innovative medicine discovery
Impact This initiative has just started
Start Year 2011
 
Description EU AIMS 
Organisation F. Hoffmann-La Roche AG
Country Global 
Sector Private 
PI Contribution This is an EU IMI initiative in autism. We lead this multicentre research network
Collaborator Contribution providinga platform for innovative medicine discovery
Impact This initiative has just started
Start Year 2011
 
Description workshops/media 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Primary Audience Public/other audiences
Results and Impact We have hosted dissemination activities for over 500 lay people, and 500 health professionals during this grant. Also our work on 'imaging diagnostics' generated worldwide media attention from TV, radio, and the written media.

We led the TV news items, and were front page news in many newspapers.
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010