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.
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.
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

Andrews DS
(2017)
In Vivo Evidence of Reduced Integrity of the Gray-White Matter Boundary in Autism Spectrum Disorder.
in Cerebral cortex (New York, N.Y. : 1991)

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

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

Azuma R
(2015)
An fMRI study of facial emotion processing in children and adolescents with 22q11.2 deletion syndrome.
in Journal of neurodevelopmental disorders

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

Balardin JB
(2015)
Decreased centrality of cortical volume covariance networks in autism spectrum disorders.
in Journal of psychiatric research

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

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

Bletsch A
(2020)
Atypical measures of diffusion at the gray-white matter boundary in autism spectrum disorder in adulthood
in Human Brain Mapping

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
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 | 03/2018 |
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 | 05/2010 |
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 | Public |
Country | United Kingdom |
Start | 08/2008 |
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 | 03/2012 |
End | 04/2017 |
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 | 04/2008 |
End | 05/2013 |
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 | 04/2008 |
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 | Belgium |
Sector | Public |
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 |