Heritability of hippocampal functional and microstructural organisation

Abstract

AbstractThe hippocampal formation is a uniquely infolded anatomical structure in the medial temporal lobe, involved in a broad range of cognitive and emotional processes. It consists of microstructually and functionally different subregions, such as subiculum (SUB), cornu ammonis (CA), and dentate gyrus (DG). Here we studied the heritability of hippocampal subfield structure and function, to dissociate genetic and environmental influences. Leveraging the twin set-up of the Human Connectome Project with multimodal neuroimaging, we show that both the functional connectivity and microstructure of hippocampal subfields were heritable. Notably, we observed a genetic relationship between hippocampal and isocortical microstructural organisation, suggesting that their microstructure is governed by shared genetic factors. Furthermore, combining structural and functional measures, we identified anterior-to-posterior and medial-to-lateral axes. Whereas posterior regions showed similar associations with isocortex between structure and function, anterior regions showed uncoupling of both metrics. Together, our findings illustrate the genetic basis of hippocampal structural and functional organisation, and suggest an uncoupling of both along their shared axes.Significance StatementThe hippocampus is a key structure in cognition and affect, and a region that is highly susceptible to pathology in common neurological and neuropsychiatric conditions. Increasing evidence suggests that the hippocampus is not a uniform structure, but one that is composed of different subregions with specific microstructural and functional properties. Here, we studied how far these patterns are heritable, in order to dissociate genetic vs environmental effects on hippocampal microstructure and function. We could show the heritability of major structural and functional axes in the hippocampus which were found to be genetically coupled with the rest of the cortex. Moreover, we find that, across subfields, anterior portions show uncoupling between structure and function. Our study provides important insights on the heritability of functional and structural axes in the hippocampal formation and how these axes may scaffold flexible adaptation to a changing environment.