The Prenatal Morphomechanic Impact of Agenesis of the Corpus Callosum on Human Brain Structure and Asymmetry

Abstract

Genetic, molecular, and physical forces together impact brain morphogenesis. The early impact of deficient midline crossing in agenesis of the Corpus Callosum (ACC) on prenatal human brain development and architecture is widely unknown. Here we analyze the changes of brain structure in 46 fetuses with ACC in vivo to identify their deviations from normal development. Cases of complete ACC show an increase in the thickness of the cerebral wall in the frontomedial regions and a reduction in the temporal, insular, medial occipital and lateral parietal regions, already present at midgestation. ACC is associated with a more symmetric configuration of the temporal lobes and increased frequency of atypical asymmetry patterns, indicating an early morphomechanic effect of callosal growth on human brain development affecting the thickness of the pallium along a ventro–dorsal gradient. Altered prenatal brain architecture in ACC emphasizes the importance of conformational forces introduced by emerging interhemispheric connectivity on the establishment of polygenically determined brain asymmetries.

Analysis of the Anatomical Variability of Fetal Brains with Corpus Callosum Agenesis

“…Hence, our method does not require tedious manual segmentations nor automatic ones, which are less reliable on brains with malformations (Fidon et al, 2021a). This is in contrast to previous studies on brains with CCA (Bénézit et al, 2015;Warren et al, 2010;Knezović et al, 2019;Tarui et al, 2018;Nakata et al, 2009;Schwartz et al, 2021), which often had fewer data and focused on specific brain areas or structures. It is also important to note that unlike most papers, our analysis is not restricted to the study of tissue volume changes.…”

“…The most common alterations include colpocephaly (Leombroni et al, 2018;Bénézit et al, 2015), which was clearly visible in the second deformation mode. Ventricles dilation and volume reduction of the occipital cortical and subcortical brain matter were uneven across hemispheres, which may reflect a tendency for abnormal brain asymmetry Schwartz et al, 2021). The observed volume reduction of the occipital region coincides with findings of decreased thickness of the cerebral wall in the lateral occipital region (Schwartz et al, 2021).…”

“…Quantitative studies of fetal brains with CCA are listed in Table 1. To the best of our knowledge, quantitative analyses of volumetric fetal MRI have been attempted in only three studies (Knezović et al, 2019;Tarui et al, 2018;Schwartz et al, 2021), with a focus on specific brain structures. (Knezović et al, 2019) measured the hippocampal volume by means of manual delineation on 3D reconstructed MRIs from 39 healthy fetuses and 46 fetuses with CCA.…”

“…Following reconstruction of the surface of the inner cortical plate, sulcal developing basins were identified and matched to healthy sulcal templates, revealing abnormalities in sulcal positions. (Schwartz et al, 2021) also explored the cortical morphology of 46 fetuses with CAA and 22 healthy fetuses. Measures of surface area, gyrification, thickness of the cerebral wall and cortical asymmetry were computed in several cerebral areas to assess differences between groups, showing reduced cerebral wall thickness and structural asymmetry in several brain regions in fetuses with CCA.…”

“…Taking advantage of these recent developments, the quantitative assessment of normal and pathological brain development has attracted growing interest (Benkarim et al, 2017). However, to this day, only few studies have investigated quantitatively anatomical alterations in fetuses with CCA (Knezović et al, 2019;Tarui et al, 2018;Schwartz et al, 2021), and their focus was on specific brain structures rather than global trends. Another limitation is the difficulty to compare fetal brains of different gestational ages, since they undergo rapid and drastic changes across pregnancy (Gholipour et al, 2017).…”