Structural and Diffusion MRI Analyses With Histological Observations in Patients With Lissencephaly.

Lana Vasung,Arthur Rezayev,Natalie Stewart,Arthi Palani,Tadashi Shiohama,Andre Van Der Kouwe,Hyuk Jin Yun,Emi Takahashi,Jacob Levman,Francois Chouinard-Decorte,Jae W Song

doi:10.3389/fcell.2019.00124

Abstract

The development of cortical convolutions, gyri and sulci, is a complex process that takes place during prenatal development. Lissencephaly, a rare genetic condition characterized by the lack of cortical convolutions, offers a model to look into biological processes that lead to the development of convolutions. Retrospective, qualitative, and quantitative analyses of structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) were performed in patients with lissencephaly (N = 10) and age-/sex-matched controls (N = 10). In order to identify microstructural correlates of structural MRI and DTI findings, postmortem brains of patients with lissencephaly (N = 4) and age-matched controls (N = 4) were also examined with histology. Patients with lissencephaly had significantly smaller gyrification index and volumes of hemispheric white and gray matter, compared to the age-/sex-matched control group. However, there was no significant difference between groups in the subcortical gray matter volumes. Although the majority of patients with lissencephaly had a preserved normal-like appearance of major fissures and primary sulci, the spatial distribution of agyric cortical regions was different in patients with lissencephaly-1 (LIS1) and doublecortin (DCX) mutations. Lastly, in patients with lissencephaly, the spatiotemporal distribution of projection pathways was preserved while short- to medium-range cortico-cortical pathways were absent or fewer in number. Our results indicate that in the patients with lissencephaly cortical system is affected more than the subcortical one.

Highlights

Is a rare genetic condition characterized by a lack of cortical convolutions
Patient age at scan, and magnetic resonance imaging (MRI) findings additional to lissencephaly were described in Supplementary Table S2
Given that patients with lissencephaly showed atypical spatiotemporal patterns of brain connectivity these findings suggest that sequential spatiotemporal development of connectivity and proper maturation of cerebral cortex most likely play a role in the process of gyrification

Summary

Introduction

Is a rare genetic condition characterized by a lack of cortical convolutions. Brain MRI and Histological Analyses of Lissencephaly lissencephaly is characterized by the “four-layered cortex” while in DCX lissencephaly the cerebral cortex displays sixlayers (Viot et al, 2004) This is important because the appearance of cortical convolutions has been linked to the intensity of neurogenic processes such as the development of radial glial scaffolding (Fernández et al, 2016) used for radial migration of neurons (Rakic, 1972), differences in the rate of increasing thickness of supragranular (I–III) vs infragranular layers (V–VI) (Armstrong et al, 1991), sequential cortical ingrowth of fibers (Kostovic and Rakic, 1990), increases in brain volume (Zilles et al, 2013), and accelerated growth of white compared to gray matter, reflecting the development of connectivity (Herculano-Houzel et al, 2010). Identifying genotype–phenotype relations in lissencephaly can provide insights into the biological processes that drive the development of cortical convolutions (Dobyns, 1987)

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Discussion

Conclusion