Abstract

The entorhinal cortex (EC) is the primary site of interactions between the neocortex and hippocampus. Studies in rodents and nonhuman primates suggest that EC can be divided into subregions that connect differentially with perirhinal cortex (PRC) vs parahippocampal cortex (PHC) and with hippocampal subfields along the proximo-distal axis. Here, we used high-resolution functional magnetic resonance imaging at 7 Tesla to identify functional subdivisions of the human EC. In two independent datasets, PRC showed preferential intrinsic functional connectivity with anterior-lateral EC and PHC with posterior-medial EC. These EC subregions, in turn, exhibited differential connectivity with proximal and distal subiculum. In contrast, connectivity of PRC and PHC with subiculum followed not only a proximal-distal but also an anterior-posterior gradient. Our data provide the first evidence that the human EC can be divided into functional subdivisions whose functional connectivity closely parallels the known anatomical connectivity patterns of the rodent and nonhuman primate EC.

Highlights

  • The entorhinal cortex (EC) is a major hub within the medial temporal lobe that mediates hippocampalneocortical communication (Buzsaki, 1996; Lavenex and Amaral, 2000)

  • Our analyses revealed that anterior-lateral and posterior-medial EC subregions exhibited distinct patterns of intrinsic functional connectivity with regions in the neocortex (PRC and parahippocampal cortex (PHC)) and hippocampal formation

  • The anterior-lateral EC (al-EC) region could be delineated on the basis of preferential connectivity with perirhinal cortex (PRC), whereas the borders of posterior-medial EC (pm-EC) were derived from connectivity with PHC

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Summary

Introduction

The entorhinal cortex (EC) is a major hub within the medial temporal lobe that mediates hippocampalneocortical communication (Buzsaki, 1996; Lavenex and Amaral, 2000). Nothing is known about how hippocampal and neocortical connectivity with the EC is organized in humans. This lack of knowledge has significantly limited the development of neurobiological theories of memory and navigation and our understanding of the clinical impact of localized EC damage in the early stages of neurodegenerative conditions such as Alzheimer’s disease (AD). Spatial information is conveyed from the postrhinal cortex (POR, thought to be homologous to the PHC in primates), which shows preferential connectivity with ‘medial EC’ (MEC). Non-spatial information is conveyed from the PRC to the ‘lateral EC’ (LEC). Projections of the LEC preferentially target the region close to the border between CA1 and subiculum (distal CA1 and proximal subiculum), whereas the MEC

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