Genetic Influence on the Sulcal Pits: On the Origin of the First Cortical Folds

Abstract

The influence of genes on cortical structures has been assessed through various phenotypes. The sulcal pits, which are the putative first cortical folds, have for long been assumed to be under tight genetic control, but this was never quantified. We estimated the pit depth heritability in various brain regions using the high quality and large sample size of the Human Connectome Project pedigree cohort. Analysis of additive genetic variance indicated that their heritability ranges between 0.2 and 0.5 and displays a regional genetic control with an overall symmetric pattern between hemispheres. However, a noticeable asymmetry of heritability estimates is observed in the superior temporal sulcus and could thus be related to language lateralization. The heritability range estimated in this study reinforces the idea that cortical shape is determined primarily by nongenetic factors, which is consistent with the important increase of cortical folding from birth to adult life and thus predominantly constrained by environmental factors. Nevertheless, the genetic cues, implicated with various local levels of heritability in the formation of sulcal pits, play a fundamental role in the normal gyral pattern development. Quantifying their influence and identifying the underlying genetic variants would provide insight into neurodevelopmental disorders.

The reliability and heritability of cortical folds and their genetic correlations across hemispheres

“…We partially confirmed the results obtained in 63 . In particular, we found several medial frontal regions strongly heritable for sulcal surface area and width; our results confirm previous studies on the central sulcus 39 , the temporal lobe 59 and the corpus callosum area 64 and are also in line with studies showing high estimated heritability in prefrontal and temporal lobes for cortical thickness and surface area [65][66][67][68][69][70][71] , especially for sulcal mean depth and sulcal width.…”

Shared genetic aetiology between cognitive performance and brain activations in language and math tasks

“…For the sake of comparison, we propose to compare our study with previously published studies. Previous heritability studies that used approximately 800 subjects from the HCP, roughly as much as in our sample, obtained standard errors between 0.06 and 0.08 for phenotypes with heritability between 0.20 and 0.45 57,58 . Using the GCTA Power Calculator 55 with the default value for the variance of the single nucleotide polymorphism (SNP) derived genetic relationship matrix of 10 -5 , this range of standard errors and heritability estimates requires a sample size of 6000-7000 unrelated individuals.…”

Enhancer locus in ch14q23.1 modulates brain asymmetric temporal regions involved in language processing

“…We performed a watershed algorithm on this group pit density, which yielded a group parcellation of the sulcal pits. We projected these group areas onto the individual meshes and identified areas denoted STS b, c, d (19). Then, we extracted the geodesic path of the vertices that follow the sulcal fundus on the white mesh between the deepest pits STS b and border STS c/d, which approximately correspond to the STAP Talaraich coordinates defined by Leroy et al (13).…”

“…We have previously examined the heritability (i.e., the genetic proportion in phenotypic variance across individuals) of STS characteristics. Because sulcal pits correspond to the deeper parts of sulci where the initial or primary folds would occur, they show less intersubject variability (19,20). In the left STAP area, the two sulcal pit regions (STS b and c in (19)) are highly heritable in contrast to the right STS yielding the largest asymmetric estimate of heritability for all brain sulci.…”

“…Because sulcal pits correspond to the deeper parts of sulci where the initial or primary folds would occur, they show less intersubject variability (19,20). In the left STAP area, the two sulcal pit regions (STS b and c in (19)) are highly heritable in contrast to the right STS yielding the largest asymmetric estimate of heritability for all brain sulci. In addition, the PPs that interrupt some sulci are more frequent and heritable in the left STS (h 2 = 0.53) than in the right (h 2 = 0.27) (17).…”