Abstract
The medial (MEC) and lateral entorhinal cortex (LEC), widely studied in rodents, are well defined and characterized. In humans, however, the exact locations of their homologues remain uncertain. Previous functional magnetic resonance imaging (fMRI) studies have subdivided the human EC into posteromedial (pmEC) and anterolateral (alEC) parts, but uncertainty remains about the choice of imaging modality and seed regions, in particular in light of a substantial revision of the classical model of EC connectivity based on novel insights from rodent anatomy. Here, we used structural, not functional imaging, namely diffusion tensor imaging (DTI) and probabilistic tractography to segment the human EC based on differential connectivity to other brain regions known to project selectively to MEC or LEC. We defined MEC as more strongly connected with presubiculum and retrosplenial cortex (RSC), and LEC as more strongly connected with distal CA1 and proximal subiculum (dCA1pSub) and lateral orbitofrontal cortex (OFC). Although our DTI segmentation had a larger medial-lateral component than in the previous fMRI studies, our results show that the human MEC and LEC homologues have a border oriented both towards the posterior-anterior and medial-lateral axes, supporting the differentiation between pmEC and alEC.
Highlights
The entorhinal cortex (EC) is a part of the medial temporal lobe, and a central structure for memory formation and navigation (Eichenbaum et al, 2007; Moser and Moser, 2013; Suzuki and Eichenbaum, 2000)
We define the medial’ entorhinal cortex (MEC) as the region that is most strongly connected with the presubiculum and/or retrosplenial cortex (RSC), while the lateral’ entorhinal cortex (LEC) is the region that is most strongly connected with dCA1pSub and/or orbitofrontal cortex (OFC) (Caballero-Bleda and Witter, 1993; Honda and Ishizuka, 2004; Hoover and Vertes, 2007; Insausti and Amaral, 2008; Jones and Witter, 2007; Kondo and Witter, 2014; Saleem et al, 2008; Witter and Amaral, 1991, 2021; Wyss and Van Groen, 1992)
A hard segmentation was performed on the normalized and thresholded voxel-wise connectivity maps using FMRIB Software Library (FSL)’s find_the_biggest (Behrens et al, 2003a; Johansen-Berg et al, 2004), meaning that the voxels that had a higher connection probability with the presubiculum/RSC than with dCA1pSub/OFC were classified as MEC, and vice versa for LEC
Summary
The entorhinal cortex (EC) is a part of the medial temporal lobe, and a central structure for memory formation and navigation (Eichenbaum et al, 2007; Moser and Moser, 2013; Suzuki and Eichenbaum, 2000). The EC can be divided into two main subregions – ‘medial’ entorhinal cortex (MEC) and ‘lateral’ entorhinal cortex (LEC) – which differ in both functional properties and connectivity with other regions (Canto et al, 2008; Kerr et al, 2007; van Strien et al, 2009). Both the function and anatomy of the EC subregions have been widely studied in rodents and non-human primates. Recent years have seen a stark increase in functional magnetic resonance imaging (fMRI) studies of the human EC (Bellmund et al, 2019; Chen et al, 2019; Montchal et al, 2019; Maass et al, 2015; Navarro Schröder et al, 2015; Reagh and Yassa, 2014; Schultz et al, 2012), the exact locations of the human homologues of MEC and LEC remain uncertain
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