White matter, the part of the brain consisting largely of nerve bundles connecting cortical areas, develops with a specific trajectory over the lifespan. New work from the Department of Psychiatry has now revealed that this trajectory may be altered in people on the autism spectrum. The paper, published in “Translational Psychiatry”, also studied the siblings of individuals with autism, which may display similar alterations. The researchers from the Brain Mapping Unit, the Autism Research Centre and the BCNI therefore propose that an altered trajectory of white matter development may be an endophenotype of autism.
The technique used in this study is termed Diffusion Tensor Imaging (DTI). It allows researchers to measure the direction and speed of diffusion of water molecules in different parts of the brain. This technique is particularly useful when studying the brain’s white matter tracts, since water molecules prefer to spread along bundles of nerves, rather than perpendicularly across those nerves.
In addition to the direction of the nerve bundles, DTI also allows researchers to measure other aspects of white matter. For example, the overall speed of diffusion, both alongside a nerve and perpendicular across it, is termed Mean Diffusivity. It was this measure which the group was interested in, since Mean Diffusivity usually decreases during adolescence in large parts of the brain.
In total, 121 adolescents took part in this research, including 43 individuals diagnosed with an autism spectrum condition (ASC), 38 siblings of individuals with ASC who had no diagnosis themselves, and 40 typically developing individuals with no family history of ASC. The adolescents were between 12 and 20 years of age, with an average age of around 15. While each individual was only scanned once, the groups spanned an age range large enough to let the researchers test age-related developments across the group.
In the 40 healthy subjects, the research group found what was expected from previous studies of how white matter develops in adolescents: Mean Diffusivity decreased in many parts of the brain over the course of development.
However, in the subjects with ASC, the group identified an area of the brain that did not develop as expected. A large area in the right hemisphere, centred on a structure known as the superior longitudinal fasciculus (SLF), showed no decreases in Mean Diffusivity throughout adolescence. The SLF connects the frontal lobe with the parietal, occipital and temporal lobes. The authors state: “Motor behaviour, visual-spatial coherence and language production, domains affected in ASC, all depend on smooth information flow in the SLF.”
The researchers propose that this difference in the way white matter develops in the SLF could point towards a mechanism by which these symptoms of ASC are produced by atypical white matter development.
Including the siblings of adolescents with ASC allowed the researchers to test if this effect is what is known as an endophenotype. Siblings share 50% of their genetic material with someone who has a diagnosis of ASC, markers of autistic neurobiology can be expected to be present to lesser degrees in them.
However, while the reduction in Mean Diffusivity in the sibling group was smaller than what was observed in the typically developing group, the effect was not statistically significant. A component of Mean Diffusivity, however, did develop significantly different in the sibling group. This points towards a possible existence of an endophenotype in white matter structure development, but remains a question to be tested by future research.