Autism spectrum disorder (ASD) is a neurodevelopmental condition characterised by social communication deficits and restricted and repetitive interests. It mostly affects males, and has a range of severities and presentations. The causes of ASD are, as yet, unknown, though research indicates that a combination of genetic and environmental factors contribute to aberrant brain structure and function. The structure of the brain can be non-invasively assessed in vivo using magnetic resonance imaging (MRI). The MRI method diffusion tensor imaging (DTI) can be used to reconstruct the brain’s white matter tracts and quantify their microstructural health. The aim of this thesis is to investigate white matter microstructure in ASD, and comprises of four studies: an investigation of the association between white matter microstructure and the spectrum of ASD traits; a study of amygdala connections and their association with ASD symptomatology; a graph theory approach to investigate the structural networks of the brain; a study of sex-based differences in brain structure in ASD, and unaffected siblings of probands. White matter microstructure was associated with ASD traits across a spectrum that incorporated healthy controls through to those with clinically-diagnosed autism. Associations between the microstructure of amygdala–cortical connections and ASD symptoms were dependent upon the brain region and ASD trait of interest. The ASD structural network was similar to that of controls, which indicates that the macromolecular arrangement of the ASD brain is relatively conserved. There were some sex-based differences in white matter microstructure in ASD, though fewer than anticipated. In conclusion, DTI techniques provide evidence that brain microstructure is compromised in ASD, and that the severity of the structural deficits is correlated with symptom severity in a specific fashion. Brain topology is relatively conserved, indicating that ASD arises from deficits in the quality of brain connections, rather than their overall arrangement
