Direct Evidence for Domain-Sensitive Functional Subregions in Human Entorhinal Cortex

The medial temporal lobes (MTL) are known to play a crucial role in memory processes. Anatomical findings from animal studies suggest partially segregated MTL pathways converge in the hippocampus, with a posterior stream including parahippocampal and medial lateral entorhinal cortex and an anterior stream including perirhinal and lateral entorhinal cortex. These streams may operate on spatial and nonspatial information, respectively. In humans, such a functional dissociation has been suggested between parahippocampal and perirhinal cortex. Data from rodents and nonhuman primates suggest a similar dissociation between medial and lateral entorhinal cortex, which are reciprocally connected to parahippocampal and perirhinal cortex, but evidence for functional subregions within entorhinal cortex in humans is lacking. We addressed this issue using high-resolution fMRI with improved spatial normalization. Volunteers (n = 28) performed a working memory paradigm involving the retrieval of spatial (scenes) and nonspatial (faces) information after distraction. A clear dissociation between MTL subcircuits emerged. A perirhinal-lateral entorhinal pathway was more involved in the retrieval of faces after distraction, whereas a parahippocampal-medial entorhinal pathway was more involved in the retrieval of scenes after distraction. A cluster in posterior hippocampus showed a deactivation for the retrieval of faces after distraction. Our data thus provide direct evidence for a functional specialization within human entorhinal cortex and thereby strongly support MTL models that emphasize the importance of partially segregated parallel processing streams.