Imaging of White Matter and Myelination in Normal and Autistic NeuroDevelopment

Broadly, brain tissue may be classified into either white or grey matter. White matter is comprised of fibers which carry information to and from specific grey matter areas where that information is processed. Surrounding these fibers is myelin, a fat layer which increases the speed information is transfered and is critical for correct and efficient brain function. Myelination, or the formation of the myelin layer, is a crucial element of brain development and the loss of myelin can significantly impair function. Another disorder in which differences in myelin may occur is autism, a brain disorder in which patients have trouble communicating, lack imagination, and show restricted or repetitive behaviour. However, when and where differences in myelination exist in the autistic brain remain open questions. This project aims to answer these key questions by investigating myelination during brain development using a non-invasive brain imaging technique. This research is important for two reasons: First, it will enable us to determine which brain regions or systems underly autistic symptoms, and secondly, by understanding the evolution of these differences during brain maturation we can make more informed choices about the timing of therapeutic interventions.

Background: Autism is a pervasive developmental disorder characterized by impairments in social, communicative and behavioural functioning. Although post-mortem and structural imaging studies have identified volume differences in specific brain regions between autistic patients and healthy controls, the neural basis of these differences remains poorly understood. One proposed candidate is aberrant white matter maturation, specifically myelination, in the autistic brain. Myelination is a key element of brain development and is essential for normal function and cognition. Despite this critical role, the time-course of myelination in autism is not well known, and the affect of atypical maturation remains a key question.



Aims: This work proposes to assess, quantitatively, myelin content and myelination throughout healthy and autistic neurodevelopment. Using a recently developed non-invasive quantitative myelin imaging technique (multi-component driven equilibrium single pulse observation of T1 and T2 - mcDESPOT) we will perform the first longitudinal investigation of normal and autistic neurodevelopment from early childhood to adolescence, exploring the hypothesis that aberrant (ie. rate and/or extent of) myelination is a neurobiological trait of the disorder.



Methods/Design: To test our hypothesis, a combined cross-sectional / longitudinal study design will be used with 192 autistic patients and healthy controls recruited from three narrowly defined age-groups: toddlers (2-4 years of age), children (6-9 years) and adolescents (12-16 years). Each participant will be scanned at least once per year (depending on age) for 3 years using mcDESPOT method as well as a conventional volumetric structural acquisition. Within each, and across all, age-group cohorts, we will investigate and compare myelination and brain volume trajectories to determine if enlarged brain regions are associated with myelination differences. Further, we will examine correlations between affected brain areas with psychological testing measures to determine which changes most accurately predict autistic symptoms.



Scientific & Medical Relevance: Despite the widespread assertion that autism is a developmental disorder, to date no longitudinal study of neurodevelopment in this condition has been performed. Results of this study will help elucidate both regional differences in autism, as well as the time-course over which such differences manifest. Such information may allow earlier and/or more specific diagnosis, and provide a means of monitoring and evaluating therapeutic interventions.