Neocortex Folding in Primates up to Human: Evolution and Mechanisms

Folding of the neocortex is a fundamental feature of brain development in many mammalian species, notably in most non-human primates and in particular in human. Cortical folding is thought to allow a larger cortical surface area, with a greater number of neurons, to fit into the limited size of the cranial cavity.

Here, we review the following key topics related to cortical folding. We first discuss the principles of cortical folding and dissect the factors contributing to the mechanical asymmetry that is thought to have a key role in driving fold formation. We then address the evolution of cortical folding and discuss the two principal types of folding, conserved and evolved, and the roles of neuron production vs. neuron migration in these. We also review the different model systems used, such as human tissue/cell-based, animal, and computational models of cortical folding.

This includes a discussion of human malformations of cortical folding, the potential of cerebral organoids to study folding, the power of the ferret model to dissect mechanisms of cortical folding, and the use of computational models to make predictions about cortical folding. Finally, we address future perspectives of folding research and outline directions that research may take.