Brain anatomy in autism; a multi-centre study

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 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.