The entorhinal cortex: an examination of cyto- and myeloarchitectonic organization in humans

The entorhinal cortex (ERC) has been implicated in the pathophysiology ofAlzheimer's disease, schizophrenia and other disorders affecting cognitivefunctions. While powerful anatomical and histochemical methods(immunohistochemistry, in situ hybridization, etc.) may be applied(although with limitations) to postmortem human brain, each analysis shouldutilize a cytoarchitectonic approach to provide appropriate comparisonswithin the subdivisions of the ERC. Accordingly, we describe here thenormal cyto- and myeloarchitecture of the human ERC as a prerequisite forthe accompanying study of this region in schizophrenia. Our parcellation ofthis cortex differs from previous treatments in three ways. First, weadopted specific criteria of inclusion to define each subdivision of theregion. Although distinctive ERC features are most prominent in theintermediate portion of this region, at least one of these features wasconsidered the minimum necessary criterion to include adjacent tissue inthe entorhinal area. Second, we used morphometric measurements (neuronalsize and density as well as subdivisional volume and laminar thickness) tosupport our qualitative evaluation. Third, we have applied to the human ERCthe conventional cytoarchitectonic nomenclature of the entorhinal cortexused previously in studies of non-human primates. This allows a moreaccurate extrapolation of the available numerous experimental anatomical,physiological and psychological data on this region to the human. As in themonkey, the five main subareas were recognized in the human (prorhinal,lateral, intermediate, sulcal and medial) but three required furthersubdivision (intermediate, sulcal and medial). The morphometric resultsobtained suggested a progression of the human entorhinal cortex from theperipheral to the central subareas, with the intermediate subarea (281) asthe most complete entorhinal subdivision. Compared with non-human primates,the human ERC not only retains the basic periallocortical organization butalso demonstrates further evolution. Taken together with availableexperimental data on the connectivity of this brain region, these resultsprovide an anatomical basis for evaluating the ERC in human behavior.