Full Length ArticleCytoarchitecture, probability maps and functions of the human frontal pole
Introduction
Brodmann area (BA) 10 is located at the frontal pole of the human brain and represents the most rostral part of the brain. It is part of the prefrontal cortex (PFC). Its large extent in the human brain as compared to other species (Semendeferi et al., 2001) makes it a candidate for processing “human-specific” functions. BA10 is involved in many higher cognitive functions such as planning of future actions and the ability to draw analogies (Fuster, 2008). There are several theories (reviewed by e.g. Ramnani and Owen (2004) or Tsujimoto et al. (2011)), like the gateway hypotheses (Burgess et al., 2005, Burgess et al., 2007) or the hypotheses of cognitive branching (Koechlin et al., 1999) which try to combine the variety of neuroimaging findings.
The precise localization of the borders of BA10 using structural or functional MRI is not possible. In contrast to the primary sensory areas with their distinct cyto- and myeloarchitecture (Zilles and Amunts, 2010, Zilles and Amunts, 2012), the relatively similar architecture of the various six-layered isocortical areas of the prefrontal cortex does not provide sufficient tissue contrast for in vivo mapping of such subtle differences. In vivo mapping approaches, which predict the localization of areal borders by cortical folding patterns work well in primary cortical areas, but are less successful in higher associative areas (Fischl et al., 2008, Fischl et al., 2009, Hinds et al., 2008, Hinds et al., 2009). Using high-field MRI and the myelin-based contrast allowed delineating the primary visual cortex (Geyer et al., 2011), but a definition of borders of higher associative cortical areas and higher sensory areas like that on the human frontal pole could not be demonstrated until now. Such MR-derived myelin maps are impaired in regions close to air/tissue interfaces, like the orbitofrontal cortex and the frontal pole adjacent to the frontal sinus (Glasser and Van Essen, 2011) because of susceptibility artifacts. Delineating cortical regions based on connectivity patterns taken from diffusion weighted MRI in living subjects is another in vivo option which might lead to localization of higher order cortical areas, but this approach requires reliably and precisely defined regions of interest for fiber tracking (Behrens and Johansen-Berg, 2005, Johansen-Berg et al., 2004). In the vast majority of areas, the delineation of cytoarchitectonic areas of the isocortex provides presently the only precise, reliable and reproducible basis for anatomical localization of functional studies and independent evaluation of structural in vivo mapping approaches.
The cytoarchitectonic map of Korbinian Brodmann (Brodmann, 1909) (Fig. 1A) shows an area BA10, occupying the frontal pole including the frontomarginal sulcus, the rostral part of the superior frontal gyrus and small parts of the middle frontal gyrus. Caudally, BA10 is bordered by middle frontal area BA46. The mesial border to BA32 is located rostral to the cingulate gyrus. The rostral end of the olfactory sulcus could be taken as a gross macroscopic landmark for the borderline to orbitofrontal area BA11 according to Brodmann's map. A comparable cytoarchitectonic map (Fig. 1B) was proposed by (von Economo and Koskinas (1925) and Sarkisov and the Russian school (Fig. 1C) (Sarkisov et al., 1949).
In a more recently published map (Öngür et al., 2003), area 10 is subdivided into three parts, 10 m, 10r, and 10p (Fig. 1D). Area 10p occupies the frontal pole, while 10 m and 10r are found on the lower part of the mesial surface of the frontal lobe. The map of Öngür and colleagues differs from the older maps by the larger extent of area 10 on the mesial surface of the brain. It shows 10 m and 10r as a broad “tongue” extending on the most ventral part of the cingulate gyrus.
Thus, the parcellations of area 10 provided by these maps differ regarding the number of subdivisions as well as the extent of the areas. This might reflect interindividual anatomical variability of the extent, and different parcellations methods and concepts in case of the number of subdivisions. The interindividual variability is an important aspect of cytoarchitectonic parcellations as shown by the probability maps of different cortical regions, e.g. various visual areas (Amunts et al., 2000, Malikovic et al., 2007), primary motor cortex (Geyer et al., 1996), primary and secondary somatosensory cortices (Eickhoff et al., 2006a, Eickhoff et al., 2006b, Geyer et al., 1999, Geyer et al., 2000, Grefkes et al., 2001), Broca's region (Amunts et al., 1999), primary auditory cortex (Morosan et al., 2001), and parietal cortex (Caspers et al., 2006, Eickhoff et al., 2006a). These factors influencing cortical parcellation schemes have been discussed elsewhere (Zilles and Amunts, 2010).
Furthermore, existing maps of the frontal pole have not been published in a format, which enables comparisons with functional imaging data in a common spatial reference system. This is important, because recent functional studies showed different activations for the lateral and medial part of the frontal pole (Burgess et al., 2003, Gilbert et al., 2007, Gilbert et al., 2010, Schilbach et al., 2010).
The aim of the present study was to investigate if the functional differentiation into a medial and lateral region within area 10 is reflected by cytoarchitecture, and to generate three-dimensional, probabilistic maps. The borders of cytoarchitectonic areas were delineated in serial histological sections of 10 postmortem brains using an observer-independent approach (Schleicher et al., 1999, Schleicher et al., 2000, Schleicher et al., 2005, Schleicher et al., 2009). Two new areas, Fp1 and Fp2, were found by quantitative cytoarchitectonic criteria, and probability maps were generated in a standard reference space, which capture the intersubject variability in localization and extent, and provide a common reference system for comparison with functional imaging data. In order to better understand the functional role of the two identified areas, these new cytoarchitectonic maps served as regions of interest for a consecutive coordinate-based meta-analysis.
Section snippets
Histological processing of postmortem brains
Ten brains, 5 females and 5 males, were obtained via the body donor program of the Department of Anatomy at the University of Düsseldorf, Germany (Table 1). Postmortem delay of brain extraction ranged between 8 and 13 h. Clinical records did not show neurological or psychiatric diseases. Written informed consent was obtained according to the body donor program by the University of Düsseldorf governed by the local ethics committee. Histological processing has been performed as previously
General characteristics
Areas Fp1 and Fp2 represent typical isocortical areas with six layers. The border between layers II and III was clear cut (Fig. 4). Layer II consisted of a high amount of granular cells, which were intermingled by pyramidal cells of very small size from layer III. Consequently, the impression of a well demarcated border to layer III was mainly caused by the much lower cell density in upper layer III as compared to layer II. Layer III showed a gradient in pyramidal cell size from superficial
Discussion
The present study entailed a three-dimensional, cytoarchitectonic map of the human frontal pole, which considers its interindividual variability. It is based on observer-independently detected borders and is available in the MNI reference space, where it can be directly compared to results of functional imaging studies. BA10 has been subdivided into two cytoarchitectonically distinct areas: area Fp1 located laterally and Fp2 located medially. The cytoarchitectonic-based map was used for a
Acknowledgments
This study was supported by the BMBF (01GW0612, K.A.). Further funding was granted by the Helmholtz Alliance for Mental Health in an Aging Society (HelMA; K.A., K.Z.) and by the Helmholtz Alliance on Systems Biology (Human Brain Model; K.Z., S.B.E.). The authors thank Katerina Semendeferi for critical review of the manuscript and for helpful discussions.
Conflict of interest
The authors declare that there is no conflict of interest.
References (104)
- et al.
Brodmann's areas 17 and 18 brought into stereotaxic space-where and how variable?
NeuroImage
(2000) - et al.
Analysis of neural mechanisms underlying verbal fluency in cytoarchitectonically defined stereotaxic space—the roles of Brodmann areas 44 and 45
NeuroImage
(2004) - et al.
Brain regions involved in prospective memory as determined by positron emission tomography
Neuropsychologia
(2001) - et al.
The role of the rostral frontal cortex (area 10) in prospective memory: a lateral versus medial dissociation
Neuropsychologia
(2003) - et al.
The gateway hypothesis of rostral prefrontal cortex (area 10) function
Trends Cogn. Sci.
(2007) - et al.
The human inferior parietal cortex: cytoarchitectonic parcellation and interindividual variability
NeuroImage
(2006) - et al.
A new SPM toolbox for combining probabilistic cytoarchitectonic maps and functional imaging data
NeuroImage
(2005) - et al.
Testing anatomically specified hypotheses in functional imaging using cytoarchitectonic maps
NeuroImage
(2006) - et al.
Analysis of neurotransmitter receptor distribution patterns in the cerebral cortex
Neuroimage
(2007) - et al.
Activation likelihood estimation meta-analysis revisited
NeuroImage
(2012)
Anatomical mapping of functional activation in stereotactic coordinate space
NeuroImage
Predicting the location of entorhinal cortex from MRI
NeuroImage
Other minds in the brain: a functional imaging study of “theory of mind” in story comprehension
Cognition
Areas 3a, 3b, and 1 of human primary somatosensory cortex
NeuroImage
Areas 3a, 3b, and 1 of human primary somatosensory cortex. Part 2. Spatial normalization to standard anatomical space
NeuroImage
Distinct functional connectivity associated with lateral versus medial rostral prefrontal cortex: a meta-analysis
NeuroImage
Human somatosensory area 2: observer-independent cytoarchitectonic mapping, interindividual variability, and population map
NeuroImage
Accurate prediction of V1 location from cortical folds in a surface coordinate system
NeuroImage
Locating the functional and anatomical boundaries of human primary visual cortex
NeuroImage
Architectonic mapping of the medial region of the human orbitofrontal cortex by density profiles
Neuroscience
Cortical pathways to the mammalian amygdala
Prog. Neurobiol.
General and specific contributions of the medial prefrontal cortex to knowledge about mental states
NeuroImage
Human primary auditory cortex: cytoarchitectonic subdivisions and mapping into a spatial reference system
NeuroImage
Common prefrontal activations during working memory, episodic memory, and semantic memory
Neuropsychologia
Contributions of the amygdala to emotion processing: from animal models to human behavior
Neuron
Observer-independent method for microstructural parcellation of cerebral cortex: a quantitative approach to cytoarchitectonics
NeuroImage
A stereological approach to human cortical architecture: identification and delineation of cortical areas
J. Chem. Neuroanat.
Frontal pole cortex: encoding ends at the end of the endbrain
Trends Cogn. Sci.
Meta-analysis of the functional neuroanatomy of single-word reading: method and validation
NeuroImage
3-D cytoarchitectonic parcellation of human orbitofrontal cortex correlation with postmortem MRI
Psychiatry Res.
Meeting of minds: the medial frontal cortex and social cognition
Nat. Rev. Neurosci.
Advances in cytoarchitectonic mapping of the human cerebral cortex
Neuroimaging Clin. N. Am.
Broca's region revisited: cytoarchitecture and intersubject variability
J. Comp. Neurol.
Cytoarchitectonic mapping of the human amygdala, hippocampal region and entorhinal cortex: intersubject variability and probability maps
Anat. Embryol. (Berl.)
Gender-specific left-right asymmetries in human visual cortex
J. Neurosci.
Relating connectional architecture to grey matter function using diffusion imaging
Philos. Trans. R. Soc. Lond. B Biol. Sci.
The human parahippocampal region: I. Temporal pole cytoarchitectonic and MRI correlation
Cereb. Cortex
Vergleichende Lokalisationslehre der Großhirnrinde in ihren Prinzipien dargestellt auf Grund des Zellenbaues
The gateway hypothesis of rostral prefrontal cortex (area 10) function
The human inferior parietal lobule in stereotaxic space
Brain Struct. Funct.
BMDP statistical software, 1988
Damage to the fronto-polar cortex is associated with impaired multitasking
PLoS One
The human parietal operculum. II. Stereotaxic maps and correlation with functional imaging results
Cereb. Cortex
Coordinate-based activation likelihood estimation meta-analysis of neuroimaging data: a random-effects approach based on empirical estimates of spatial uncertainty
Hum. Brain Mapp.
Cortical folding patterns and predicting cytoarchitecture
Cereb. Cortex
Opinion: mapping context and content: the BrainMap model
Nat. Rev. Neurosci.
Frontal lobe and cognitive development
J. Neurocytol.
The Prefrontal Cortex
The microstructural border between the motor and the cognitive domain in the human cerebral cortex
Adv. Anat. Embryol. Cell Biol.
Two different areas within the primary motor cortex of man
Nature
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