Aim of project - The aim of the project is to gain more insight in the involvement of white matter tracts in the pathophysiology of autism.

Theoretical background - Autism is a neurodevelopmental disorder characterised by significant impairment in social, communicative, and behavioural functioning. The syndrome is clinically heterogeneous, with a wide range of symptoms and involves a varying severity of impairments. The exact aetiology of autism still remains to be determined.

Results from neuroimaging and post mortem studies suggest that functional and structural abnormalities in several brain regions are associated with autism. One of the most replicated neuroanatomical findings is an increase in head size and brain volume in autistic patients.

Besides exploring brain volume changes (global and regional), focus is now also on connectivity within the brain. Neuropsychological profiles and data from functional MRI studies have led to the hypothesis that autism may be related to a loss of functional connectivity between brain regions. Findings suggest that autism may involve preserved and possibly enhanced function of individual cortical centres, while simultaneously involving poor integration of information at higher levels of processing that require more co-ordination among cortical centres. This calls for examining the structural connections in the brain, formed by white matter.

Up until now it was only possible to investigate white matter volume, providing little information on actual connectivity between structures or regions. However, diffusion tensor imaging (DTI) permits direct assessment of white matter fiber bundles in the brain, by allowing for the quantification of the diffusion of water molecules in multiple directions. DTI thus provides an approach for quantifying the anatomical connectivity in the brain.

Approach to research aims

– This project focuses on the hypothesis that white matter tracts in the brain are affected in autism. In order to test this hypothesis, subjects with autism and healthy controls will be asked to participate in a structural MRI session, including a DTI scan. All subjects will be clinically characterised and diagnosed using standard research interviews and IQ will be assessed. To investigate differences in development of white matter tracts, subjects will be asked to participate twice with a scan interval time of approximately 1½ - 2 years. 

References

Courchesne E.  Brain development in autism: early overgrowth followed by premature arrest of growth. Ment Retard Dev Disabil Res Rev. 2004;10(2):106-11.

Herbert MR, Ziegler DA, Deutsch CK, O'Brien LM, Lange N, Bakardjiev A, Hodgson J, Adrien KT, Steele S, Makris N, Kennedy D, Harris GJ, Caviness VS Jr. Dissociations of cerebral cortex, subcortical and cerebral white matter volumes in autistic boys. Brain. 2003 May;126(Pt 5):1182-92.

Just MA, Cherkassky VL, Keller TA, Minshew NJ. Cortical activation and synchronization during sentence comprehension in high-functioning autism: evidence of underconnectivity. Brain. 2004 Aug;127(Pt 8):1811-21