Brain Pathways in LIS1-Associated Lissencephaly Revealed by Diffusion MRI Tractography

Abstract

Lissencephaly (LIS) is a rare neurodevelopmental disorder with severe symptoms caused by abnormal neuronal migration during cortical development. It is caused by both genetic and non-genetic factors. Despite frequent studies about the cortex, comprehensive elucidation of structural abnormalities and their effects on the white matter is limited. The main objective of this study is to analyze abnormal neuronal migration pathways and white matter fiber organization in LIS1-associated LIS using diffusion MRI (dMRI) tractography. For this purpose, slabs of brain specimens with LIS (n = 3) and age and sex-matched controls (n = 4) were scanned with 3T dMRI. Our high-resolution ex vivo dMRI successfully identified common abnormalities across the samples. The results revealed an abnormal increase in radially oriented subcortical fibers likely associated with radial migration pathways and u-fibers and a decrease in association fibers in all LIS specimens.