Autism spectrum disorder (ASD) is prevalent in tuberous sclerosis complex (TSC), occurring in approximately 50% of patients, and is hypothesized to be caused by disruption of neural circuits early in life. Tubers, or benign hamartomas distributed stochastically throughout the brain, are the most conspicuous of TSC neuropathology, but have not been consistently associated with ASD. Widespread neuropathology of the white matter, including deficits in myelination, neuronal migration, and axon formation, exist and may underlie ASD in TSC.

In our research, we have used structural MRI, diffusion MRI and histopathology to improve our understanding of the alterations in the neural circuits that are present in patients with Tuberous Sclerosis Complex. We are studying their association with symptoms and adverse neurological outcomes.

It is not clear at what age microstructural pathology is present in key neural circuits. We sought to identify the neural circuits associated with ASD in TSC by identifying white matter microstructural deficits in a prospectively recruited, longitudinally studied cohort of TSC infants. We identified a pattern of underconnectivity across multiple white matter fiber bundles that develops over the first 2 years of life in subjects with TSC and ASD. More details are described in our paper TSC and ASD paper and TSC and ASD paper.