GENETIC AND MORPHOLOGICAL FACTORS IN CORTICAL FOLDING: STUDIES ON THE ROLANDIC FISSURE

Martinet S¹, Pizzagalli F¹ and Vercelli A¹ | ¹Department of Neuroscience “Rita Levi Montalcini”, Neuroscience Institute Cavalieri Ottolenghi, University of Turin, Italy

Human cortical folding plays a crucial role in neurodevelopment and cognition. In this study, we analyzed several features of the cerebral sulci that describe their morphology, investigated their genetic correlations, and explored typical patterns of the central sulcus. The genetic and morphological factors underlying variations in sulcal shape remain poorly understood. To address this issue, for simplicity’s sake, we focused on the central fissure of Rolando. This sulcus was chosen because it appears around the 20th week of gestation; this means that, in the case of early alterations during gestation or in the perinatal period, it may present long-lasting developmental anomalies. Furthermore, the morphology of the central sulcus has been associated with neurological and neurodevelopmental disorders, including stroke, cerebral palsy, and amyotrophic lateral sclerosis (ALS). Since 1995, attempts have been made to morphologically classify the central sulcus, specifically the Hand Motor Cortex (HMC), following the model of Yousry et al., who defined the «omega» shape (Ω) and the «epsilon» shape (ε). Recent studies by Caulo et al. and Wu et al. have identified three new morphological variants of the HMC: medially asymmetric epsilon (mae), laterally asymmetric epsilon (lae), and null (n). The goal of this work was to validate Caulo et al.’s morphological classification by applying it to the ABCD study population (children aged 9 to 10 years) using MRI data, thus expanding the reference sample. We manually classified a subset of 1,193 individuals, including both right- and left-handed individuals. Subsequently, the central fissure was automatically segmented using BrainVISA software, ensuring standardized sulcus identification across all subjects. Since the most frequent morphological categories were the «omega» and «epsilon», we focused on these two. A Random Forest model was used to automatically classify the remaining 10,000 subjects. The most frequent shape in both hemispheres was the «⍵» category, followed by «ε». The «n», «mae», and «lae» variants were less common. These results suggest the predominance of specific morphological configurations of the central sulcus among individuals. Furthermore, in our study, we used SOLAR-Eclipse to estimate the heritability of different shapes of the central sulcus by analyzing the genetic architecture of this structure. We tested the heritability of parameters such as width, length, depth, and surface area of the central sulcus, as well as the total surface area of the cortex and its mean thickness. The results showed that the mean cortical surface area had the highest heritability value, while the parameter with the lowest estimate was the length of the central fissure. Sulcus-based heritability analysis showed significant values in multiple sulcal regions, with the sulcal width and surface area exhibit greater heritability. We found that the morphology of the central sulcus, particularly in the right hemisphere, has a modest but significant genetic basis. The close correlation between brain structure and genetic factors may contribute to genetic susceptibility to diseases that compromise the integrity of the cortex.