Architectonic Areas Research Articles

Cytoarchitectonic and connection stripes in the dysgranular insular cortex in the macaque monkey.

The insula has been classically divided into broad granular, dysgranular, and agranular architectonic sectors. We previously proposed a novel partition, dividing each sector into four to seven sharply delimited architectonic areas, with the dysgranular areas being possibly further subdivided into subtle horizontal partitions or "stripes." In architectonics, discrete subparcellations are prone to subjective variability and need being supported with additional neuroanatomical methods. Here, using a secondary analysis of indirect connectional data in the rhesus macaque monkey, we examined the spatial relationship between the dysgranular architectonic stripes and tract-tracing labeling patterns produced in the insula with injections of neuronal tracers in other cortical regions. The injections consistently produced sharply delimited patches of anterograde and/or retrograde labeling, which formed stripes across consecutive coronal sections of the insula. While the overall pattern of labeling on individual coronal sections varied with the injection site, the boundaries of the patches consistently coincided with architectonic boundaries on an adjacent cyto- (Nissl) and/or myelo- (Gallyas) architectonic section. This overlap supports the existence of a fine dysgranular stripe-like partition of the primate insula, with possibly major implications for interoceptive processing in primates including humans. The modular organization of the insula could underlie a serial stream of integration from a dorsal primary interoceptive cortex toward progressively more ventral egocentric "self-agency" and allocentric "social" dysgranular processing units.

Scalable mapping of myelin and neuron density in the human brain with micrometer resolution

Optical coherence tomography (OCT) is an emerging 3D imaging technique that allows quantification of intrinsic optical properties such as scattering coefficient and back-scattering coefficient, and has proved useful in distinguishing delicate microstructures in the human brain. The origins of scattering in brain tissues are contributed by the myelin content, neuron size and density primarily; however, no quantitative relationships between them have been reported, which hampers the use of OCT in fundamental studies of architectonic areas in the human brain and the pathological evaluations of diseases. Here, we built a generalized linear model based on Mie scattering theory that quantitatively links tissue scattering to myelin content and neuron density in the human brain. We report a strong linear relationship between scattering coefficient and the myelin content that is retained across different regions of the brain. Neuronal cell body turns out to be a secondary contribution to the overall scattering. The optical property of OCT provides a label-free solution for quantifying volumetric myelin content and neuron cells in the human brain.

Tertiary sulci, transcriptomics, and functional gradients in human cortex

Understanding how the anatomical structure of the brain across spatial scales generates a flexible infrastructure of functional representations subserving the complex aspects of human cognition is a major goal of neuroanatomists, cognitive neuroanatomists, and cognitive neuroscientists. Traditionally, it is well‐accepted that deep, primary indentations in the cerebral cortex, or sulci, serve as landmarks of functional and architectonic areas in primary sensory cortex, but not in association cortex. Nevertheless, findings from the last decade show that shallow, tertiary sulci that emerge late in gestation and continue to develop after birth serve as landmarks identifying microarchitectonic and functional transitions in human visual association cortex (Weiner, 2019, The Anatomical Record), which is consistent with classic anatomical theories (Sanides, 1964, Neuropsychologia). What factors might explain this unexpected anatomical‐functional coupling across spatial scales in visual association cortex? In this talk, I will first briefly summarize a series of studies from my lab revealing the contribution of gene expression (e.g. transcriptomics) in both the arealization of cortical hierarchies, as well as the topological layout of functional maps within areas. I will then discuss additional studies from my lab showing that the anatomical‐functional correspondences identified in human visual association cortex also a) extend to lateral prefrontal and posterior cingulate cortices and b) have behavioral implications. Finally, I will show how the combination of these findings have immediate translational, developmental, and evolutionary applications for understanding how the hominoid brain efficiently leverages shallow, rather than deep, sulci to house cognitively, microarchitectonically, and functionally complex transitions in association cortices ‐ a cortical organization that enables a fast read‐out of neural information that contributes to efficient human behavior.

Targeted Stimulation of Human Orbitofrontal Networks Disrupts Outcome-Guided Behavior.

Outcome-guided behavior requires knowledge about the current value of expected outcomes. Such behavior can be isolated in the reinforcer devaluation task, which assesses the ability to infer the current value of specific rewards after devaluation. Animal lesion studies demonstrate that orbitofrontal cortex (OFC) is necessary for normal behavior in this task, but a causal role for human OFC in outcome-guided behavior has not been established. Here, we used sham-controlled, non-invasive, continuous theta-burst stimulation (cTBS) to temporarily disrupt human OFC network activity by stimulating a site in the lateral prefrontal cortex that is strongly connected to OFC prior to devaluation of food odor rewards. Subjects in the sham group appropriately avoided Pavlovian cues associated with devalued food odors. However, subjects in the stimulation group persistently chose those cues, even though devaluation of food odors themselves was unaffected by cTBS. This behavioral impairment was mirrored in changes in resting-state functional magnetic resonance imaging (rs-fMRI) activity such that subjects in the stimulation group exhibited reduced OFC network connectivity after cTBS, and the magnitude of this reduction was correlated with choices after devaluation. These findings demonstrate the feasibility of indirectly targeting the human OFC with non-invasive cTBS and indicate that OFC is specifically required for inferring the value of expected outcomes.

Topographic organization of connections between prefrontal cortex and mediodorsal thalamus: Evidence for a general principle of indirect thalamic pathways between directly connected cortical areas

Our ability to act flexibly, according to goals and context, is known as cognitive control. Hierarchical levels of control, reflecting different levels of abstraction, are represented across prefrontal cortex (PFC). Although the mediodorsal thalamic nucleus (MD) is extensively interconnected with PFC, the role of MD in cognitive control is unclear. Tract tracer studies in macaques, involving subsets of PFC areas, have converged on coarse MD-PFC connectivity principles; but proposed finer-grained topographic schemes, which constrain interactions between MD and PFC, disagree in many respects. To investigate a unifying topographic scheme, we performed probabilistic tractography on diffusion MRI data from eight macaque monkeys, and estimated the probable paths connecting MD with each of all 19 architectonic areas of PFC. We found a connectional topography where the orderly progression from ventromedial to anterior to posterolateral PFC was represented from anteromedial to posterolateral MD. The projection zones of posterolateral PFC areas in MD showed substantial overlap, and those of ventral and anteromedial PFC areas in MD overlapped. The exception was cingulate area 24: its projection zone overlapped with projections zones of all other PFC areas. Overall, our data suggest that nearby, functionally related, directly connected PFC areas have partially overlapping projection zones in MD, consistent with a role for MD in coordinating communication across PFC. Indeed, the organizing principle for PFC projection zones in MD appears to reflect the flow of information across the hierarchical, multi-level PFC architecture. In addition, cingulate area 24 may have privileged access to influence thalamocortical interactions involving all other PFC areas.

Gender differences in cerebral metabolism for color processing in mice: A PET/MRI Study.

IntroductionColor processing is a central component of mammalian vision. Gender-related differences of color processing revealed by non-invasive functional transcranial Doppler ultrasound suggested right hemisphere pattern for blue/yellow chromatic opponency by men, and a left hemisphere pattern by women.Materials and MethodsThe present study measured the accumulation of [18F]fluorodeoxyglucose ([18F]FDG) in mouse brain using small animal positron emission tomography and magnetic resonance imaging (PET/MRI) with statistical parametric mapping (SPM) during light stimulation with blue and yellow filters compared to darkness condition.ResultsPET revealed a reverse pattern relative to dark condition compared to previous human studies: Male mice presented with left visual cortex dominance for blue through the right eye, while female mice presented with right visual cortex dominance for blue through the left eye. We applied statistical parametric mapping (SPM) to examine gender differences in activated architectonic areas within the orbital and medial prefrontal cortex and related cortical and sub-cortical areas that lead to the striatum, medial thalamus and other brain areas. The metabolic connectivity of the orbital and medial prefrontal cortex evoked by blue stimulation spread through a wide range of brain structures implicated in viscerosensory and visceromotor systems in the left intra-hemispheric regions in male, but in the right-to-left inter-hemispheric regions in female mice. Color functional ocular dominance plasticity was noted in the right eye in male mice but in the left eye in female mice.ConclusionsThis study of color processing in an animal model could be applied in the study of the role of gender differences in brain disease.

Three-Dimensional Digital Template Atlas of the Macaque Brain.

We present a new 3D template atlas of the anatomical subdivisions of the macaque brain, which is based on and aligned to the magnetic resonance imaging (MRI) data set and histological sections of the Saleem and Logothetis atlas. We describe the creation and validation of the atlas that, when registered with macaque structural or functional MRI scans, provides a straightforward means to estimate the boundaries between architectonic areas, either in a 3D volume with different planes of sections, or on an inflated brain surface (cortical flat map). As such, this new template atlas is intended for use as a reference standard for macaque brain research. Atlases and templates are available as both volumes and surfaces in standard NIFTI and GIFTI formats.

A map of the human neocortex showing the estimated overall myelin content of the individual architectonic areas based on the studies of Adolf Hopf

During the period extending from 1910 to 1970, Oscar and Cécile Vogt and their numerous collaborators published a large number of myeloarchitectonic studies on the cortex of the various lobes of the human cerebrum. In a previous publication [Nieuwenhuys et al (Brain Struct Funct 220:2551–2573, 2015; Erratum in Brain Struct Funct 220: 3753–3755, 2015)], we used the data provided by the Vogt–Vogt school for the composition of a myeloarchitectonic map of the entire human neocortex. Because these data were derived from many different brains, a standard brain had to be introduced to which all data available could be transferred. As such the Colin 27 structural scan, aligned to the MNI305 template was selected. The resultant map includes 180 myeloarchitectonic areas, 64 frontal, 30 parietal, 6 insular, 17 occipital and 63 temporal. Here we present a supplementary map in which the overall density of the myelinated fibers in the individual architectonic areas is indicated, based on a meta-analysis of data provided by Adolf Hopf, a prominent collaborator of the Vogts. This map shows that the primary sensory and motor regions are densely myelinated and that, in general, myelination decreases stepwise with the distance from these primary regions. The map also reveals the presence of a number of heavily myelinated formations, situated beyond the primary sensory and motor domains, each consisting of two or more myeloarchitectonic areas. These formations were provisionally designated as the orbitofrontal, intraparietal, posterolateral temporal, and basal temporal dark clusters. Recently published MRI-based in vivo myelin content mappings show, with regard to the primary sensory and motor regions, a striking concordance with our map. As regards the heavily myelinated clusters shown by our map, scrutiny of the current literature revealed that correlates of all of these clusters have been identified in in vivo structural MRI studies and appear to correspond either entirely or largely to known cytoarchitectonic entities. Moreover, functional neuroimaging studies indicate that all of these clusters are involved in vision-related cognitive functions.

Cerebal sulci and gyri are intrinsic landmarks for brain navigation in individual subjects: an instrument to assist neurosurgeons in preserving cognitive function in brain tumour surgery (Commentary on Zlatkina etal.).

Cerebal sulci and gyri are intrinsic landmarks for brain navigation in individual subjects: an instrument to assist neurosurgeons in preserving cognitive function in brain tumour surgery (Commentary on Zlatkina etal.).

Architecture and morphology of the human ventromedial prefrontal cortex.

A previous report identified the location of comparable architectonic areas in the ventral frontal cortex of the human and macaque brains [S. Mackey & M. Petrides (2010) Eur. J. Neurosci., 32, 1940-1950]. The present article provides greater detail with regard to the definition of architectonic areas within the ventromedial part of the human ventral frontal cortex and describes their location: (i) in Montreal Neurological Institute proportional stereotactic space; and (ii) in relation to sulcal landmarks. Structural magnetic resonance scans of four brains were obtained before the preparation of the histological specimens, so that the architectonic parcellation could be reconstructed in its original three-dimensional volume. The areal density of individual cortical layers was sampled quantitatively in the ventromedial prefrontal cortex of eight brains (16 hemispheres). The agranular cortex along the ventral edge of the corpus callosum and posterior margin of the ventromedial surface is replaced by a graded series of increasingly granular and more complexly laminated areas that succeed one another in a posterior-to-anterior direction. In parallel, the width of the supragranular layers (i.e. layers II and III) increases as compared with the infragranular layers (i.e. layers V and VI) from posterior to anterior. A measure of how rapidly cortical features change at areal boundaries also showed that the rate of change in the granule and pyramidal cell densities of layers IV and V, respectively, was greater at the borders between posterior areas than between anterior areas. This article will facilitate the anatomical identification and comparison of experimental data involving the human vmPFC.

Modular architectonic organization of the insula in the macaque monkey

In order to provide a framework for ongoing analyses of the neuronal connections of the insular cortex of the macaque monkey using modern high-resolution methods, we examined its anatomical organization in serial coronal sections stained alternately with Nissl and Gallyas (myelin) techniques. We observed the same 15 distinct architectonic areas in 10 brains. Within the granular, dysgranular, and agranular regions described in prior studies, we identified 4, 4, and 7 distinct areas, respectively. Across brains, these areas have consistent architectonic characteristics, and in flat map reconstructions they display a consistent topological or neighborhood arrangement, despite variations in the size of individual areas between cases. The borders between areas are generally rather sharply defined. Some areas, in particular the dysgranular areas, appear to consistently contain subtle transitions that suggest possible subareas or modules within the well-delimited areas. The presence of a distinct granular area that straddles the fundus of the superior limiting sulcus over its entire posterior-to-anterior extent is consistent with the available evidence on interoceptive thalamocortical projections, and also with the tensile anchor theory of species-specific cortical gyrification. These observations are consonant with the model of homeostatic afferent processing in the primate insula, and they suggest that discrete modules within insular cortex provide the basis for its polymodal integration of all salient activity relevant to ongoing emotional behavior.

Blockface histology with optical coherence tomography: A comparison with Nissl staining

Spectral domain optical coherence tomography (SD-OCT) is a high resolution imaging technique that generates excellent contrast based on intrinsic optical properties of the tissue, such as neurons and fibers. The SD-OCT data acquisition is performed directly on the tissue block, diminishing the need for cutting, mounting and staining. We utilized SD-OCT to visualize the laminar structure of the isocortex and compared cortical cytoarchitecture with the gold standard Nissl staining, both qualitatively and quantitatively. In histological processing, distortions routinely affect registration to the blockface image and prevent accurate 3D reconstruction of regions of tissue. We compared blockface registration to SD-OCT and Nissl, respectively, and found that SD-OCT-blockface registration was significantly more accurate than Nissl-blockface registration. Two independent observers manually labeled cortical laminae (e.g. III, IV and V) in SD-OCT images and Nissl stained sections. Our results show that OCT images exhibit sufficient contrast in the cortex to reliably differentiate the cortical layers. Furthermore, the modalities were compared with regard to cortical laminar organization and showed good agreement. Taken together, these SD-OCT results suggest that SD-OCT contains information comparable to standard histological stains such as Nissl in terms of distinguishing cortical layers and architectonic areas. Given these data, we propose that SD-OCT can be used to reliably generate 3D reconstructions of multiple cubic centimeters of cortex that can be used to accurately and semi-automatically perform standard histological analyses.

Comparative Anatomy of Marmoset and Mouse Cortex from Genomic Expression

Advances in mouse neural circuit genetics, brain atlases, and behavioral assays provide a powerful system for modeling the genetic basis of cognition and psychiatric disease. However, a critical limitation of this approach is how to achieve concordance of mouse neurobiology with the ultimate goal of understanding the human brain. Previously, the common marmoset has shown promise as a genetic model system toward the linking of mouse and human studies. However, the advent of marmoset transgenic approaches will require an understanding of developmental principles in marmoset compared to mouse. In this study, we used gene expression analysis in marmoset brain to pose a series of fundamental questions on cortical development and evolution for direct comparison to existing mouse brain atlas expression data. Most genes showed reliable conservation of expression between marmoset and mouse. However, certain markers had strikingly divergent expression patterns. The lateral geniculate nucleus and pulvinar in the thalamus showed diversification of genetic organization between marmoset and mouse, suggesting they share some similarity. In contrast, gene expression patterns in early visual cortical areas showed marmoset-specific expression. In prefrontal cortex, some markers labeled architectonic areas and layers distinct between mouse and marmoset. Core hippocampus was conserved, while afferent areas showed divergence. Together, these results indicate that existing cortical areas are genetically conserved between marmoset and mouse, while differences in areal parcellation, afferent diversification, and layer complexity are associated with specific genes. Collectively, we propose that gene expression patterns in marmoset brain reveal important clues to the principles underlying the molecular evolution of cortical and cognitive expansion.

Cyto-, myelo- and chemoarchitecture of the prefrontal cortex of the Cebus monkey

BackgroundAccording to several lines of evidence, the great expansion observed in the primate prefrontal cortex (PfC) was accompanied by the emergence of new cortical areas during phylogenetic development. As a consequence, the structural heterogeneity noted in this region of the primate frontal lobe has been associated with diverse behavioral and cognitive functions described in human and non-human primates. A substantial part of this evidence was obtained using Old World monkeys as experimental model; while the PfC of New World monkeys has been poorly studied.In this study, the architecture of the PfC in five capuchin monkeys (Cebus apella) was analyzed based on four different architectonic tools, Nissl and myelin staining, histochemistry using the lectin Wisteria floribunda agglutinin and immunohistochemistry using SMI-32 antibody.ResultsTwenty-two architectonic areas in the Cebus PfC were distinguished: areas 8v, 8d, 9d, 12l, 45, 46v, 46d, 46vr and 46dr in the lateral PfC; areas 11l, 11m, 12o, 13l, 13m, 13i, 14r and 14c in the orbitofrontal cortex, with areas 14r and 14c occupying the ventromedial corner; areas 32r, 32c, 25 and 9m in the medial PfC, and area 10 in the frontal pole. This number is significantly higher than the four cytoarchitectonic areas previously recognized in the same species. However, the number and distribution of these areas in Cebus were to a large extent similar to those described in Old World monkeys PfC in more recent studies.ConclusionsThe present parcellation of the Cebus PfC considerably modifies the scheme initially proposed for this species but is in line with previous studies on Old World monkeys. Thus, it was observed that the remarkable anatomical similarity between the brains of genera Macaca and Cebus may extend to architectonic aspects. Since monkeys of both genera evolved independently over a long period of time facing different environmental pressures, the similarities in the architectonic maps of PfC in both genera are issues of interest. However, additional data about the connectivity and function of the Cebus PfC are necessary to evaluate the possibility of potential homologies or parallelisms.

Quantitative demonstration of comparable architectonic areas within the ventromedial and lateral orbital frontal cortex in the human and the macaque monkey brains

The orbital and ventromedial frontal cortical regions of the human and the macaque monkey brains include several spatially discrete areas which are defined histologically by their distinctive laminar architecture. Although considerable information has been collected on the function and anatomical connections of specific architectonic areas within the orbital and ventromedial frontal cortex of the macaque monkey, the location of comparable areas in the human brain remains controversial. We re-examined the comparability of orbital and ventromedial frontal areas across these two species and provide the first quantitative demonstration of architectonically comparable cortical areas in the human and the macaque brains. Images of Nissl-stained sections of the cortex were obtained at low magnification. Differences in the typical size of neurons in alternating pyramidal and granule cell layers were exploited to segregate the cortical layers before sampling. Profiles of areal neuronal density were sampled across the width of the cortex. The location of individual cortical layers was identified on each profile by sampling a set of equally sized images on which the cortical layers had been manually traced. The rank order of sampled architectonic features in comparable architectonic areas in the two species was significantly correlated. The differences in measured features between gyral and sulcal parts of the same architectonic area are at a minimum 3-4 times smaller than the differences between architectonic areas for the areas examined. Furthermore, the quantified architectonic features arrange areas within the orbital and ventromedial frontal cortex along two dimensions: an anterior-to-posterior and a medial-to-lateral dimension. On the basis of these findings, and in light of known anatomical connections in the macaque, this region of the human cortex appears to comprise at least two hierarchically structured networks of areas.

Statistical Analysis of Parieto-Frontal Cognitive-Motor Networks

Considerable information has been gathered on the anatomical connectivity within the parieto-frontal network of the primate brain. To examine the statistical regularities in this connectivity, we carried out hierarchical cluster analysis and found statistically significant clusters of areas: four in the parietal and six in the frontal lobe. Clusters were based on patterns of inputs from all cortical areas. Both parietal and frontal clusters were composed of sets of spatially contiguous architectonic areas. The four parietal clusters were composed of sets of anterior (somatosensory), dorsal, inferior, and medio-lateral parietal cortical areas. The six frontal clusters were composed of sets of dorsal premotor, ventral premotor, primary motor, cingulate motor, and dorsal and ventral prefrontal cortical areas. Furthermore, connectivity between frontal and parietal clusters was topographic and reciprocal. Thus we found substantial statistical structure and organization in the parieto-frontal network that gives a simplified but accurate description of this system.

Cortical Connections of the Macaque Caudal Ventrolateral Prefrontal Areas 45A and 45B

We have found that the 2 architectonic subdivisions of the prefrontal area 45, 45A and 45B, display connectivity patterns that clearly distinguish them from one another and from their neighboring architectonic areas. Area 45A is primarily connected to the frontal areas 45B, 12l, caudal 12r, 12o, 10, rostrodorsal 46, 9/8B, 44, 8/FEF (frontal eye field), and the SEF (supplementary eye field), temporal area IPa, and unique among all the studied areas, to the superior temporal polysensory (STP) area and auditory parabelt areas. Area 45B displayed much stronger frontal connections with the oculomotor areas 8/FEF, 8r, and the SEF than those of area 45A, primary connections with areas 12l, caudal 12r, 12o, and 8B, and unlike area 45A, with areas ventrorostral 46, rostral 12r, 12m, and 13m. Temporal connections were all virtually confined to areas IPa, intermediate TEa/m, and TE. Additional labeling was found in lateral intraparietal area. Our data suggest that 45A and 45B are 2 distinct areas, possibly playing a differential role in nonspatial information processing: area 45A corresponds to the prefrontal sector for which a role in communication behavior and homology with the human area 45 was proposed, whereas area 45B is a distinct prearcuate area, possibly affiliated to the oculomotor frontal system.

Architectonic mapping of the medial region of the human orbitofrontal cortex by density profiles

The study of architectonic differentiation in the cortex is advanced by the articulation of objective definitions based on clear features of the cortical architecture. We adopted areal density profiles as a means of sampling the cortex. On the profiles, we isolated and quantified the density of individual cortical layers. These features may serve as criteria in objective definitions in a way that builds on qualitative observations found in the classical literature. A preprocessing procedure was introduced to overcome artefacts in the density profiles caused by the partial overlap of neighboring neuronal layers and cortical folding. We applied this method to the medial half of the orbital frontal cortex in specimens drawn from 10 human postmortem brain hemispheres. The measurements successfully confirmed the existence of several qualitatively observed areas (architectonic areas 14c, 14r, 11m, 11 and 13). The selection of specific sampling parameters was justified on the basis of simultaneous measurements of the cortical morphology which demonstrate its influence on the appearance of the cortical layers. We also examined the robustness of the measuring procedure by analyzing the outcome of varying systematically the sampling parameters. We describe here a novel method of sampling the cortex for architectonic analysis and demonstrate its application on histological sections obtained from the medial half of the human orbitofrontal cortex.

Architectonic distribution of the serotonin transporter within the orbitofrontal cortex of the vervet monkey

To elucidate the organization of the serotoninergic innervation within the orbitofrontal cortex (OFC), serotonin transporter (SERT) density was quantified by autoradiography using [ 3H]cyanoimipramine binding. In six adult vervet monkeys, 15 architectonic areas were delineated according to cytoarchitectonic (Nissl), myeloarchitectonic (Gallyas) and chemoarchitectonic (acetylcholinesterase) criteria to assess SERT distribution at two levels of organization: cortical area and cortical type. For cortical type, the 15 areas were evenly divided into three different categories primarily based upon the degree of granularization of layer IV: agranular, dysgranular, and granular. Within agranular and dysgranular, but not granular cortical types, SERT density was area-specific and progressively decreased in a medial to lateral gradient. Across cortical types, SERT density decreased in a caudal to rostral gradient: agranular>dysgranular>granular. A similar caudal to rostral gradient was seen when serotonin content was measured (using high performance liquid chromatography) in areas representative of each cortical type. Collectively, these results suggest that the serotoninergic innervation is organized according to both cortical type and area, and is thus structured to differentially modulate information processing within the OFC.

A new SPM toolbox for combining probabilistic cytoarchitectonic maps and functional imaging data

Correlating the activation foci identified in functional imaging studies of the human brain with structural (e.g., cytoarchitectonic) information on the activated areas is a major methodological challenge for neuroscience research. We here present a new approach to make use of three-dimensional probabilistic cytoarchitectonic maps, as obtained from the analysis of human post-mortem brains, for correlating microscopical, anatomical and functional imaging data of the cerebral cortex. We introduce a new, MATLAB based toolbox for the SPM2 software package which enables the integration of probabilistic cytoarchitectonic maps and results of functional imaging studies. The toolbox includes the functionality for the construction of summary maps combining probability of several cortical areas by finding the most probable assignment of each voxel to one of these areas. Its main feature is to provide several measures defining the degree of correspondence between architectonic areas and functional foci. The software, together with the presently available probability maps, is available as open source software to the neuroimaging community. This new toolbox provides an easy-to-use tool for the integrated analysis of functional and anatomical data in a common reference space.