A bstract The parahippocampus-hippocampus complex in the mesiotemporal lobe (MTL) is implicated in many different cognitive processes, is compromised in numerous disorders, and exhibits a unique cytoarchitectural transition from six-layered isocortex to three-layered allocortex. Our study leveraged an ultra-high-resolution histological reconstruction of a human brain to (i) develop a continuous surface model of the MTL iso-to-allocortex transition and (ii) quantitatively characterise the region’s cytoarchitecture. We projected the model into the native space of in vivo functional magnetic resonance imaging of healthy adults to (iii) construct a generative model of its intrinsic circuitry and (iv) determine its relationship with distributed functional dynamics of macroscale isocortical fluctuations. We provide evidence that the most prominent axis of cytoarchitectural differentiation of the MTL follows infolding from iso-to-allocortex and is defined by depth-specific variations in neuron density. Intrinsic effective connectivity exhibited a more complex relationship to MTL geometry, varying across both iso-to-allocortical and anterior-posterior axes. Variation along the long axis of the MTL was associated with differentiation between transmodal and unimodal systems, with anterior regions linked to transmodal cortex. In contrast, the iso-to-allocortical gradient was associated with the multiple demand system, with isocortex linked to regions activated when task demands prohibit the use of prior knowledge. Our findings establish a novel model of the MTL, in which its broad influence on neural function emerges through the combination micro- and macro-scale structural features.

Convergence of cortical types and functional motifs in the mesiotemporal lobe