Elsevier

NeuroImage

Volume 25, Issue 3, 15 April 2005, Pages 975-992
NeuroImage

Subdivisions of human parietal area 5 revealed by quantitative receptor autoradiography: a parietal region between motor, somatosensory, and cingulate cortical areas

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Abstract

Brodmann's area (BA) 5 of the human superior parietal cortex occupies a central anatomical position between the primary motor (BA 4), somatosensory (area 3b and BA 2), cingulate (area 23c), and superior parietal association cortex (BA 7). We studied the regional and laminar distributions of the binding sites of 12 different neurotransmitter receptors (glutamatergic: AMPA, kainate, NMDA; GABAergic: GABAA, GABAB; cholinergic: muscarinic M2, nicotinic; adrenergic: α1, α2; serotoninergic: 5-HT1A, 5-HT2; dopaminergic: D1) in human postmortem brains by means of quantitative receptor autoradiography, since the structural and functional aspects of human BA 5 are widely unknown, and previous observations have demonstrated characteristic differences in receptor distribution between motor and somatosensory areas. Binding site densities were measured in the cytoarchitectonically defined BA 5 and surrounding regions. Similarities and differences of receptor distribution between cortical areas were studied by cluster analysis of mean binding site densities averaged over all cortical layers, univariate and multivariate statistics, and by density profiles representing laminar receptor distribution patterns. Based on regional heterogeneities of binding site densities and of the cytoarchitecture within BA 5, we suggest a subdivision into three subareas: medial area 5M, lateral area 5L, and area 5Ci in the region around the cingulate sulcus. BA 5 is therefore a heterogeneous cortical region, comprising three subareas showing receptor expression patterns similar to the adjoining higher order somatosensory, multimodal parietal, or cingulate regions. These findings suggest that human BA 5 constitutes a higher order cortical area, clearly distinct from the primary somatosensory and motor cortex.

Introduction

Several maps of the human cerebral cortex show an area representing the most rostral part of the superior parietal lobe (SPL), which is distinct from the posteriorly adjacent parietal cortex (Batsch, 1956, Brodmann, 1909, Gerhardt, 1940, Sarkissov et al., 1955, Vogt, 1911, von Economo and Koskinas, 1925). This is Brodmann's (1909) cytoarchitectonic area (BA) 5, and Vogt's (1911) myeloarchitectonic area 75 (Fig. 1). von Economo and Koskinas (1925) denominated it area PA2 and described the cytoarchitectonic pattern of this region as being very similar to their area PA1, which is comparable to a region nowadays referred to as area 3a (Fig. 1) (Zilles and Palomero-Gallagher, 2001). Area 3a is found in the fundus of the central sulcus between BA 4 (primary motor cortex) and area 3b (primary somatosensory cortex). Brodmann (1909) considered his areas BA 3 and BA 5 to be clearly distinct of each other, whereas von Economo and Koskinas (1925) concluded that area PA2 (BA 5) is the medial and posterior extension of area PA1 (area 3a) on the free cortical surface (Fig. 1). Consequently, following von Economo's and Koskinas' line of thought, BA 5 should display an organization intermediate between the primary motor (BA 4) and the somatosensory (area 3b) cortex. In terms of the precise anatomical location of BA 5, particularly regarding its relation to the postcentral sulcus, differences exist, however, between the maps of the abovementioned authors (Fig. 1).

The macaque SPL comprises areas PE (rostrally) and PEc (caudally) (Pandya and Seltzer, 1982) (Fig. 2). Area PE, which corresponds to macaque BA 5 (Brodmann, 1909), occupies, in contrast to human BA 5, most of the SPL. Area PEc, which corresponds to part of BA 7 (Brodmann, 1909), is much smaller than area PE/BA 5. According to Brodmann (1909) the rest of macaque BA 7 constitutes the inferior parietal lobe and most of the medial parietal lobe.

The interspecies homologies between the areas of human and macaque SPL are controversially discussed in the literature. Brodmann (1909) thought that human and macaque BAs 5 are homologous, whereas macaque BA 7 is the common source of human BAs 7, 39, and 40 (Mountcastle et al., 1975, Vogt and Vogt, 1919). Other authors suggest a direct equivalency of the human SPL and IPL with those of the macaque (Eidelberg and Galaburda, 1984, Galletti et al., 2003, Pandya and Seltzer, 1982, von Bonin and Bailey, 1947, von Economo and Koskinas, 1925).

In both species a major function of the SPL is the integration of somatosensory and visual information for implementation of visually perceived spatial information into motor programs, which also rely on proprioceptive feedback from the body parts (Battaglia-Mayer et al., 2003, Chouinard et al., 2003, Iacoboni and Zaidel, 2004, Lacquaniti and Caminiti, 1998, Otsuki et al., 1999, Stephan et al., 1995). Human BA 5 lies centrally between the primary motor, somatosensory, cingulate, and posterior parietal association cortex (PPC) (Fig. 1). In humans, somatosensory stimulation can activate BA 5 and motor responses can be elicited by stimulation of BA 5 (Allison et al., 1996, Lim et al., 1994, Richer et al., 1993). It is not clear whether human BA 5 functionally belongs to the primary somatosensory cortex (areas 3a and 3b), as suggested by von Economo and Koskinas (1925), or to the higher order somatosensory cortex (BA 2) or PPC, or even to the motor or cingulate cortex. To address this question, we analyzed the regional and laminar distribution patterns of neurotransmitter receptors in BA 5 and its neighboring areas by means of quantitative receptor autoradiography. This method has proven not only to be a powerful tool for parcellating the cerebral cortex, but also enables tracing of functional aspects of different cortical areas. Areas with similar functional properties have a similar receptor architecture, i.e., a similar balance between the densities of the different receptors (Geyer et al., 1996, Geyer et al., 1997, Geyer et al., 1998, Mash et al., 1988, Zilles and Clarke, 1997, Zilles and Palomero-Gallagher, 2001, Zilles et al., 2002a, Zilles et al., 2002b). Therefore, the similarities of these receptor expression patterns between BA 5 and primary as well as higher order somatosensory, primary motor, and higher order association cortical areas may reflect the position of BA 5 within the organizational structure of this central cortical region.

Section snippets

Materials and methods

Four postmortem human brains were obtained at autopsy (3 females, 1 male, mean age = 71.8 years, age range = 61–77 years, mean postmortem delay = 12.3 h, postmortem delay range = 8–18 h) and analyzed by means of quantitative in vitro receptor autoradiography. All subjects had given written consent before death, had been included in the body donor program of the Department of Anatomy at the University of Düsseldorf, and had no record of neurological or psychiatric diseases. The right hemispheres

Cytoarchitecture of BA 5

On the lateral surface of the hemisphere, BA 5 was localized in the rostral wall of the postcentral sulcus and always replaced BA 2 near the interhemispheric fissure (Fig. 3A). The most dorsal part of lateral BA 5 occasionally reached the crown of the postcentral gyrus rostrally. The posterior border of most dorsal lateral BA 5 was not completely determined in all brains. It tended to reach the posterior wall of the postcentral sulcus or the cortical surface near the lateral branch of the

Discussion

The aim of the present study was an analysis of the cyto- and receptor architecture of BA 5 and a comparison of its architecture with that of the surrounding areas of the motor, somatosensory, cingulate, and posterior parietal association cortex.

According to the present observation, lateral BA 5 is located in the postcentral sulcus near the interhemispheric fissure. Microstructurally, BA 5 is found posterior and medial to BA 2, replacing the latter area on the anterior wall of the postcentral

Acknowledgments

This Human Brain Project/Neuroinformatics research is funded by the National Institute of Biomedical Imaging and Bioengineering, the National Institute of Neurological Disorders and Stroke, and the National Institute of Mental Health.

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