Resident Physician University of Pittsburgh Pittsburgh, Pennsylvania, United States
Introduction: The human insula has a unique and highly-conserved geometry that is dramatically different from all other lobes. Understanding the embryological origin of the insula is crucial to understanding insular anatomy and to inform the pathogenesis of insular epilepsy and gliomas. We analyze lobar geometry in adults and during fetal development and identify a novel mechanism for the formation of the insula.
Methods: Using a in utero fetal MRI atlas of 81 healthy fetuses and adult MRI (N=107), we modeled cortical development and designed a novel spherical projection algorithm to analyze migration pathways to the insula. In addition, we used fetal diffusion tractography to demonstrate the existence of a novel curved migration pathway to the insula.
Results: The adult insular gyri are significantly different than the folds in any other lobe and these differences appear during fetal development. Specifically, the insula exhibits shallower sulci (p <.0001) and less complex surface (p <.0001) throughout fetal development. In utero, insular volume demonstrates logistic growth an order of magnitude slower than the other lobes. In spherical projection, the lenticular nuclei obstruct 60-70% of radial pathways from the ventricular zone (VZ) to the insula compared to the other lobes (p <.01), forcing curved/tangential migration to the insula in contrast to a radial pathway. Fetal diffusion tractography identifies streams of putative insular progenitor cells that originate from the VZ near the pallial-subpallial boundary and migrate tangentially around the lenticular nuclei to form the insula that have significantly different shape than radial migration (p <.001)
Conclusion : Our findings challenge existing theories of cortical development through radial migration and demonstrate that an alternative mechanism forms the insula. This not only underpins the relative slow growth of the insula, overgrowth of the operculae, and closure of the Sylvian fissure but also explains the unique anatomy of the insula and the overall shape of the human brain.
