3-D Cytoarchitectonic parcellation of human orbitofrontal cortex

Abstract

The orbitofrontal cortex (OFC) is located on the basal surface of the frontal lobe and is distinguished by its unique anatomical and functional features. Clinical and postmortem studies suggest the involvement of the orbitofrontal cortex in psychiatric disorders. However, the exact parcellation of this cortical region is still a matter of debate. Therefore, the goal of this study is to provide a detailed description of the extent of borders of individual orbitofrontal cortical areas using cytoarchitectonic criteria in a large sample of human brains, which could be applied by independent neuroanatomists. To make this microscopic parcellation useful to neuroimaging studies, magnetic resonance images of postmortem brains in the coronal plane were collected prior to the preparation of coronal histological sections from the same brains. A complete series of coronal sections from 6 normal human brains and partial sections from the frontal cortex of 21 normal human brains were stained with general histological and immunohistochemical methods specific for different cell-types. These sections were examined microscopically by two independent neuroanatomists (HBMU and GR) to achieve reproducible delineations. After the borders were determined, the tissue sections were superimposed on the corresponding magnetic resonance images. Based on our cytoarchitectonical criteria, Brodmann's areas 47 and 11 were included in the human orbitofrontal cortex. Area 47 was further subdivided into three medial (located on the medial, anterior and posterior orbital gyri) and two lateral (located on the lateral orbital gyrus) subareas. In addition, we observed an anterior–posterior gradient in the cytoarchitecture of areas 11 and 47. The transverse orbital sulcus corresponds roughly to the transition between the subregions of the anterior and posterior OFC. Finally, the present delineation is contrasted with an overview of the different published nomenclatures for the OFC parcellation.

Introduction

The orbitofrontal cortex (OFC) is located on the basal surface of the frontal lobe and constitutes one of the subregions of the prefrontal cortex. The OFC is distinguished by its unique anatomical and functional specialization (Fuster, 2008, Cavada et al., 2000, Roberts, 2006, Man et al., 2009). Behavioral, neuropsychological and functional neuroimaging studies reveal that OFC is involved in the control of emotional, motivational, cognitive flexibility and social behavior (for excellent reviews, see Kringelbach and Rolls, 2004, Kringelbach, 2005, Rolls and Grabenhorst, 2008). Recent neuroimaging reports, also indicate that OFC plays a critical role in psychopathology of severe mental disorders such as schizophrenia, depression, bipolar illness, obsessive compulsive disorder and drug addiction (Blumberg et al., 1999, Crespo-Facorro et al., 2000, Baxter et al., 2000, Drevets, 2001, Bremner et al., 2002, Lacerda et al., 2004, Völlm et al., 2004, Remijnse et al., 2006, Van den Heuvel et al., 2009). Moreover, postmortem histopathological studies indicate that the OFC is a site of neuronal and glial cell pathology in psychiatric disorders (Rajkowska et al., 1999, Rajkowska et al., 2005, Rajkowska et al., 2007, Cotter et al., 2002, Cotter et al., 2005). These morphometrical and stereological studies of the OFC require a description of well-defined cytoarchitectonic characteristics of individual OFC areas and borders for their delineation. Non-human primate studies show that the OFC consists of different (sub)areas with a distinct pattern of cortical and subcortical connections and unique cytoarchitecture (Barbas and Pandya, 1989, Preuss and Goldman-Rakic, 1991, Carmichael and Price, 1994, Cavada et al., 2000, Öngür and Price, 2000, Petrides and Pandya, 2001, Barbas et al., 2002, Barbas and Zikopoulos, 2006, Barbas, 2007, Roberts et al., 2007). Existing parcellations of the human OFC confirm its heterogeneity, but also reveal that the human OFC is more complex than that of non-human primates and that a simple extrapolation of subdivisions from monkey to human brain is not straightforward (Beck, 1949, Petrides and Pandya, 2001, Öngür et al., 2003, Uylings et al., 2005a; see Fig. 1).

Another difficulty in understanding the parcellation of the human OFC stems from the fact, that there is no agreement between different researchers on the position, extent and nomenclature of individual OFC areas. This is illustrated in Fig. 1, which shows seven different parcellations of the human OFC. A main reason for discrepancies in the location of OFC areas between different maps is that most authors do not provide detailed description of the cytoarchitectonic criteria used to distinguish individual OFC areas as well as the location of their borders (e.g., Brodmann, 1909, Brodmann, 1914). These problems have been given adequate attention in three studies (Von Economo and Koskinas, 1925, Kononova, 1935, Öngür et al., 2003). However, these three studies cannot be easily compared with each other since individual OFC areas on the respective maps vary in their location and extent and are specified with a different nomenclature. Therefore, the goal of the present study is to provide a set of cytoarchitectonic criteria for the delineation of individual OFC areas so that their respective borders can be reproduced by independent, experienced neuroanatomists. This is essential for stereological studies in these OFC areas applying Nissl staining for, for example, cell counting and for the interpretation of neuroimaging studies on normal and diseased brains. Herewith we prefer a nomenclature in which a cortical area is indicated with a particular Brodmann area number, while a subdivision of a cortical area is indicated with a suffix added to the pertinent Brodmann area number. This implies, that the differences between cortical areas having a different Brodmann number are larger than between the subdivisions of a particular Brodmann area. In addition, we combine the microscopic cytoarchitectonic parcellation with immunocytochemical stainings for neurofilaments (SMI-32 and NF200) and calcium binding proteins (parvalbumin and calbindin). Moreover, the cytoarchitectonic parcellation carried out on postmortem histological sections is displayed in corresponding sections from postmortem MRI scans of the pertinent cases. These sections with delineated borders of individual OFC areas are further used for 3-D reconstructions which reveal inter-individual variability in the location and extent of human OFC (e.g., Uylings et al., 2005a). In addition, using our cytoarchitectonic knowledge on the microscopic location of the OFC and its individual subdivisions, we were able to define their macroscopic localization on structural MRI by using the gyral and sulcal pattern as an additional guide. We will discuss that such an approximation of OFC areas in structural MRI is preferable above a derivation of OFC areas on the basis of a Talairach-like atlases of human cerebral cortex.