Cortical gyrification and its relationships with molecular measures and cognition in children with the FMR1 premutation

Abstract

Neurobiological basis for cognitive development and psychiatric conditions remains unexplored in children with the FMR1 premutation (PM). Knock-in mouse models of PM revealed defects in embryonic cortical development that may affect cortical folding. Cortical-folding complexity quantified using local gyrification index (LGI) was examined in 61 children (age 8–12 years, 19/14 male/female PM carriers, 15/13 male/female controls). Whole-brain vertex-wise analysis of LGI was performed for group comparisons and correlations with IQ. Individuals with aberrant gyrification in 68 cortical areas were identified using Z-scores of LGI (hyper: Z ≥ 2.58, hypo: Z ≤ − 2.58). Significant group-by-sex-by-age interaction in LGI was detected in right inferior temporal and fusiform cortices, which correlated negatively with CGG repeat length in the PM carriers. Sixteen PM boys (hyper/hypo: 7/9) and 10 PM girls (hyper/hypo: 2/5, 3 both) displayed aberrant LGI in 1–17 regions/person while 2 control boys (hyper/hypo: 0/2) and 2 control girls (hyper/hypo: 1/1) met the same criteria in only 1 region/person. LGI in the precuneus and cingulate cortices correlated positively with IQ scores in PM and control boys while negatively in PM girls and no significant correlation in control girls. These findings reveal aberrant gyrification, which may underlie cognitive performance in children with the PM.

The Epigenome in Neurodevelopmental Disorders

“…As bRGCs are highly prominent in humans and mammals with a high rate of gyrification, such as ferrets, while being rather few in number in lissencephalic species such as the mouse ( Penisson et al, 2019 ; Subramanian et al, 2020 ), bRGCs have been associated with the generation of cerebral gyrification and are of critical importance for cortical folding. In addition to that, gyrification is hypothesized to be determined by neuro- and gliogenesis, progenitor cell density, cellular migration, and the formation of cortical connections with respect to individual regions of gyri and sulci ( Penisson et al, 2019 ; Wang et al, 2020 ). In line with the aforementioned terminology, the RGCs and IPCs present in the human and murine ventricular zone (VZ) are named apical IPCs (aIPCs) and apical radial glial cells (aRGCs) ( García-Moreno et al, 2012 ; Sun and Hevner, 2014 ).…”