Use of Brodmann’s map in a standardized human brain (Talairach and Tournoux, 1988
) led to wide acceptance of this view of cortical organization. The nomenclature, however, was not based on the histology of the atlas case, the original map poorly represented sulcal areas on the convoluted surface and many areas were not cytologically uniform. A histological study of area 2 recently assessed postmortem brains with magnetic resonance imaging (Grefkes et al., 2002) and emphasizes an important direction for standardizing regions of interest based on their cytology. In addition, many cytological studies show heterogeneity of Brodmann areas (1909)
. Midcingulate cortex (MCC), for example, is the posterior part of areas 24 and 32 and areas 24 and 23 have dorsoventral subdivisions (Vogt, 1993
; Vogt et al., 1995
). In terms of connections, MCC receives more inferior parietal and less amygdala input than does the perigenual cortex (Vogt and Pandya, 1987
) and MCC contains the cingulate motor areas (CMAs), including the primitive gigantopyramidal field of Braak (1976
; Matelli et al., 1991
; Zilles et al., 1995
; Vogt et al., 1995
). The CMAs have high densities of glutamate, muscarinic M1, serotonin 1, and α-adrenoceptors compared to the supplementary motor areas (Zilles et al., 1995
; Roland and Zilles, 1996
). In addition, the CMAs project directly to the spinal cord (Dum and Strick, 1993
) and motor cortices (Morecraft and Van Hoesen, 1998
; Van Hoesen et al., 1993
) and they are involved in response selection and reorganizing behavior for changing rewards (Shima and Tanji, 1998
; Bush et al., 2002
). Thus, human and experimental animal findings support a more complex organization of the cingulate gyrus than suggested by Brodmann’s map.
Three lines of evidence suggest that MCC itself is comprised of two parts. First, there are two structurally unique CMAs in the cingulate sulcus with different neuronal response properties and connections. The caudal CMA (cCMA) has neurons with short latencies to muscle contractions during passive driving and projects to the same part of the striatum as primary motor cortex, while the rostral CMA (rCMA) has neurons with long-durations between discharge and contraction associated with self-paced movements and projections overlap in the striatum with those from the pre-supplementary motor area (Shima et al., 1991
; Takada et al., 2001
). The presence of two motor areas also suggests unique afferent circuits for their separate engagement. Second, the cingulate gyral surface has different cytologies like cortex in the sulcus and Smith (1907)
and the Vogts (1919)
identified anterior and posterior divisions in this region. shows these maps because so few perspectives beyond Brodmann’s are considered in imaging research. Third, a unique class of spindle neuron occurs in the anterior but not posterior parts of MCC (Nimchinsky et al., 1995
; their ) and this supports the hypothesis of a functional dichotomy in MCC.
Figure 1 Two maps of cingulate cortex showing multiple rostrocaudal subdivisions (from Braak, 1980) rather than only anterior and posterior divisions reported by Brodmann. These maps raise questions about transitional cortex between Brodmann’s areas 23 (more ...)
Figure 3 Features of MCC areas a24’ and p24’ for both “a” and “b” subdivisions in NeuN and SMI32 of Case 2. Of particular note are the higher densities of NFP-expressing neurons in deep layer III (SMI32; below double (more ...)
An important issue regarding the midcingulate region is the nature of transition between areas 24 and 23. Area 24 is agranular (i.e., lacks a layer IV), while area 23 is granular because it has this layer. If there are two MCC divisions, which one is agranular, does this transition involve a simple increase in the number of layer IV neurons, and are there unique laminar cytologies for each subarea? Although Brodmann (1909)
placed the border between areas 24 and 23 at a level approximately half-way between the genu and splenium of the corpus callosum, this border may be more posterior (Vogt et al., 1995
, 1997, 2003
). Since Brodmann’s border for areas 24 and 23 is used in functional imaging, documentation of MCC heterogeneity and posterior transitions will have a profound impact on localization research.
A striking finding of human imaging research is the consistent activation of MCC during acute noxious stimulation (Derbyshire, 2000
; Peyron et al., 2000
). Although noxious activation of the MCC skeletomotor region suggests a role in motor response selection, particularly as it relates to recoding of inappropriate behaviors that produce painful outcomes (Vogt et al., 1996
; Davis et al., 1997
), it may not explain the affective component of pain processing. Early positron emission tomography (PET) studies assessed healthy women while they self-generated sad events and activated perigenual ACC (pACC), however, middle, posterior, and retrosplenial cortices were not active (George et al. 1995
). Indeed, these sites were quite distant from the MCC activity reported in the pain literature and a recent analysis of emotion showed that MCC was virtually inactive (Phan et al., 2002
). In spite of these many advances, no studies directly link pACC and MCC areas to pain and emotion functions and no joint analyses of pain and emotion have been correlated with modern morphological findings.
The present investigation evaluates structural heterogeneity within MCC, defines the transitional features of cortex between anterior and posterior cingulate cortices, and correlates these areas with activations during pain and simple emotions. The cytology of areas 24 and 23 and transitional features between them was evaluated with Nissl and immunohistochemical preparations, digital macrophotographs of each medial surface were co-registered to Talairach and Tournoux (1988)
coordinates, regional borders identified, and the average position of each border from the vertical plane at the anterior commissure calculated. One functional analysis plotted noxious cutaneous thermal activations in relation to the MCC borders and a second plotted responses during simple emotions induced with scripts or facial expressions, while a control analysis identified active sites using similar stimuli that were content neutral. The joint pain and emotion analysis resolves some key questions about the unique contributions of the rCMA and cCMA and reciprocally connected gyral surface areas to behavior.