Integration of microstructural and functional aspects of human somatosensory areas 3a, 3b, and 1 on the basis of a computerized brain atlas.

In this study we analyzed structural and functional aspects of the human primary somatosensory areas 3a, 3b, and 1 on the basis of a computerized brain atlas. The approach overcomes many of the problems associated with subjective architectonic parcellations of the cortex and with 'classical" brain maps published in a "rigid" print format. Magnetic resonance (MR) scans were obtained from ten postmortem brains. The brains were serially sectioned at 20 microm, and sections were stained for cell bodies. Areas 3a, 3b, and 1 were delineated statistically on the basis of differences in the laminar densities of neuronal cell bodies. The borders of the areas were topographically variable across different brains and did not match macroanatomical landmarks of the postcentral gyrus. After correction of the sections for deformations due to histological processing, each brain's 3-D reconstructed histological volume and the volume representations of areas 3a, 3b, and 1 were adapted to the reference brain of a computerized atlas and superimposed in 3-D space. For each area, a population map was generated that described, for each voxel, how many brains had a representation of that area. Despite considerable interindividual variability, representations of areas 3a, 3b, and 1 in > or = 50% of the brains were found in the fundus of the central sulcus, in the rostral bank, and on the crown of the postcentral gyrus, respectively. For each area, a volume of interest (VOI) was defined that encompassed that area's representation in > or = 50% of the brains. Despite close spatial relationship in the postcentral gyrus, the three VOIs overlapped by < 1% of their volumes. Changes in regional cerebral blood flow (rCBF) were measured with positron emission tomography when six right-handed subjects discriminated differences in the speed of a rotating brush stimulating the palmar surface of the right hand. With co-registered MR images, the rCBF data were adapted to the same reference brain and superimposed with the microstructural VOIs. Discrimination of moving stimuli, contrasted to rest, increased the rCBF in the VOIs of areas 3b and 1, but not in area 3a. This approach opens up the possibility of (1) defining VOIs of cortical areas which are not based on macroanatomical landmarks but instead on observer-independent cytoarchitectonic mapping of postmortem brains and of (2) determining in these VOIs changes in rCBF data obtained from functional imaging experiments.

Activation in the ipsilateral posterior parietal cortex during tool use: a PET study.

The basis of perceptual assimilation of tool and hand has been considered to be in modification of body schemata, for which integration of multimodal sensory information about our body parts is required. Using positron emission tomography and H(2)(15)O, we aimed to identify brain regions that change their neural activity in association with changes in neural processing of visual and/or somatosensory information when humans use a simple tool. Normal subjects were instructed to manipulate a small graspable object with a pair of tongs or with the fingers of their right or left hand. The only site activated during manipulation with the tool, compared with the fingers, with the right hand was the lateral edge of the right intraparietal sulcus (IPS). During manipulation using the left hand with the tool, compared with using the fingers, an area in the middle part of the left IPS was activated. Areas in the contralateral hemisphere were activated during both the tool-use and the finger-use tasks compared to the control task, but there was no statistically significant difference between the tool-use and the finger-use tasks. Therefore, the results suggest that the ipsilateral posterior parietal cortex was recruited during the tool-use tasks to integrate visuosomatosensory information.

Variability and asymmetry in the human precentral motor system. A cytoarchitectonic and myeloarchitectonic brain mapping study.

The morphology of the region of the primary motor cortex in the human brain is variable, and putative asymmetries between the hemispheres have been noted since the beginning of last century. Such variability may confound the results of clinical lesion or functional activation studies. We measured Brodmann area (BA) 4 and the identifiable precentral component of the pyramidal tract (PRPT) in 11 human post-mortem brains using techniques of quantitative cytoarchitectonic and myeloarchitectonic image analysis. Topography and variability in the localization of architectonic borders were analysed and mapped to a computerized spatial reference system, which consists of an individual in vivoMRI brain. All maps were superimposed to produce probabilistic maps of BA 4 and PRPT which can be co-registered with any image of brain structure or function that has also been transformed to Talairach coordinates. These maps can be readily applied to future brain mapping studies. We observed a considerable degree of variability between hemispheres (intra-individual) and between brains (inter-individual). The variation zones of BA 4 and PRPT differ from the templates of the Talairach atlas. Voxel-based morphometry shows significant side differences with larger volumes of PRPT in the left hemisphere than in the right hemisphere. This larger volume of the descending cortical motor fibres may be related to the known left-hemisphere dominance for handedness in >90% of the population. In contrast, BA 4 was symmetrically organized. The lack of a significant correlation between the size of BA 4 and the size of PRPT may relate to the fact that additional non-primary motor and sensory cortices contribute to the origins and size of the pyramidal tract proper.

A probabilistic atlas and reference system for the human brain: International Consortium for Brain Mapping (ICBM).

Motivated by the vast amount of information that is rapidly accumulating about the human brain in digital form, we embarked upon a program in 1992 to develop a four-dimensional probabilistic atlas and reference system for the human brain. Through an International Consortium for Brain Mapping (ICBM) a dataset is being collected that includes 7000 subjects between the ages of eighteen and ninety years and including 342 mono- and dizygotic twins. Data on each subject includes detailed demographic, clinical, behavioural and imaging information. DNA has been collected for genotyping from 5800 subjects. A component of the programme uses post-mortem tissue to determine the probabilistic distribution of microscopic cyto- and chemoarchitectural regions in the human brain. This, combined with macroscopic information about structure and function derived from subjects in vivo, provides the first large scale opportunity to gain meaningful insights into the concordance or discordance in micro- and macroscopic structure and function. The philosophy, strategy, algorithm development, data acquisition techniques and validation methods are described in this report along with database structures. Examples of results are described for the normal adult human brain as well as examples in patients with Alzheimer's disease and multiple sclerosis. The ability to quantify the variance of the human brain as a function of age in a large population of subjects for whom data is also available about their genetic composition and behaviour will allow for the first assessment of cerebral genotype-phenotype-behavioural correlations in humans to take place in a population this large. This approach and its application should provide new insights and opportunities for investigators interested in basic neuroscience, clinical diagnostics and the evaluation of neuropsychiatric disorders in patients.

Human somatosensory area 2: observer-independent cytoarchitectonic mapping, interindividual variability, and population map.

We analyzed the topographical variability of human somatosensory area 2 in 10 postmortem brains. The brains were serially sectioned at 20 microm, and sections were stained for cell bodies. Area 2 was delineated with an observer-independent technique based on significant differences in the laminar densities of cell bodies. The sections were corrected with an MR scan of the same brain obtained before histological processing. Each brain's histological volume and representation of area 2 was subsequently reconstructed in 3-D. We found that the borders of area 2 are topographically variable. The rostral border lies between the convexity of the postcentral gyrus and some millimeters deep in the rostral wall of the postcentral sulcus. The caudal border lies between the fundus of the postcentral sulcus and some millimeters above it in the rostral wall. In contrast to Brodmann's map, area 2 does not extend onto the mesial cortical surface or into the intraparietal sulcus. When the postcentral sulcus is interrupted by a gyral bridge, area 2 crosses this bridge and is not separated into two segments. After cytoarchitectonic analysis, the histological volumes were warped to the reference brain of a computerized atlas and superimposed. A population map was generated in 3-D space, which describes how many brains have a representation of area 2 in a particular voxel. This microstructurally defined population map can be used to demonstrate activations of area 2 in functional imaging studies and therefore help to further understand the role of area 2 in somatosensory processing.

A four-dimensional probabilistic atlas of the human brain.

The authors describe the development of a four-dimensional atlas and reference system that includes both macroscopic and microscopic information on structure and function of the human brain in persons between the ages of 18 and 90 years. Given the presumed large but previously unquantified degree of structural and functional variance among normal persons in the human population, the basis for this atlas and reference system is probabilistic. Through the efforts of the International Consortium for Brain Mapping (ICBM), 7,000 subjects will be included in the initial phase of database and atlas development. For each subject, detailed demographic, clinical, behavioral, and imaging information is being collected. In addition, 5,800 subjects will contribute DNA for the purpose of determining genotype- phenotype-behavioral correlations. The process of developing the strategies, algorithms, data collection methods, validation approaches, database structures, and distribution of results is described in this report. Examples of applications of the approach are described for the normal brain in both adults and children as well as in patients with schizophrenia. This project should provide new insights into the relationship between microscopic and macroscopic structure and function in the human brain and should have important implications in basic neuroscience, clinical diagnostics, and cerebral disorders.

Activation reduction in anterior temporal cortices during repeated recognition of faces of personal acquaintances.

Repeated recognition of the face of a familiar individual is known to show semantic repetition priming effect. In this study, normal subjects were repeatedly presented faces of their colleagues, and the effect of repetition on the regional cerebral blood flow change was measured using positron emission tomography. They repeated a set of three tasks: the familiar-face detection (F) task, the facial direction discrimination (D) task, and the perceptual control (C) task. During five repetitions of the F task, familiar faces were presented six times from different views in a pseudorandom order. Activation reduction through the repetition of the F tasks was observed in the bilateral anterior (anterolateral to the polar region) temporal cortices which are suggested to be involved in the access to the long-term memory concerning people. The bilateral amygdala, the hypothalamus, and the medial frontal cortices, were constantly activated during the F tasks, and considered to be associated with the behavioral significance of the presented familiar faces. Constant activation was also observed in the bilateral occipitotemporal regions and fusiform gyri and the right medial temporal regions during perception of the faces, and in the left medial temporal regions during the facial familiarity detection task, which are consistent with the results of previous functional brain imaging studies. The results have provided further information about the functional segregation of the anterior temporal regions in face recognition and long-term memory.

Probabilistic mapping and volume measurement of human primary auditory cortex.

Despite their potential utility in clinical and research settings, the range of intra- and interindividual variations in size and location of cytoarchitectonically defined human primary auditory cortex (PAC) is largely unknown. This study demonstrates that gyral patterns and the size and location of PAC vary independently to a considerable degree. Thus, the cytoarchitectonic borders of PAC cannot be reliably inferred from macroscopic-MR visible-anatomy. Given the remarkable topographical variability of architectonic areal borders, standard brain mapping which is made solely on the basis of macroanatomic landmarks may lead to structural-functional mismatch. Consequently, interpretations of individual auditory activity patterns might often be inaccurate. In view of the anatomic discrepancies, we generated probability maps of PAC in which the degree of intersubject overlap in each stereotaxic position was quantified. These maps show that the location of PAC in Talairach space differs considerably between hemispheres and individuals. In contrast to earlier cytoarchitectonic work which is based in most cases on studies of single brains, our systematic approach provides extensive microanatomic data as a reference system for studies of human auditory function.

Human primary auditory cortex: cytoarchitectonic subdivisions and mapping into a spatial reference system.

The transverse temporal gyrus of Heschl contains the human auditory cortex. Several schematic maps of the cytoarchitectonic correlate of this functional entity are available, but they present partly conflicting data (number and position of borders of the primary auditory areas) and they do not enable reliable comparisons with functional imaging data in a common spatial reference system. In order to provide a 3-D data set of the precise position and extent of the human primary auditory cortex, its putative subdivisions, and its topographical intersubject variability, we performed a quantitative cytoarchitectonic analysis of 10 brains using a recently established technique for observer-independent definition of areal borders. Three areas, Te1.1, Te1.0, and Te1.2, with a well-developed layer IV, which represent the primary auditory cortex (Brodmann area 41), can be identified along the mediolateral axis of the Heschl gyrus. The cell density was significantly higher in Te1.1 compared to Te1.2 in the left but not in the right hemisphere. The cytoarchitectonically defined areal borders of the primary auditory cortex do not consistently match macroanatomic landmarks like gyral and sulcal borders. The three primary auditory areas of each postmortem brain were mapped to a spatial reference system which is based on a brain registered by in vivo magnetic resonance imaging. The integration of a sample of postmortem brains in a spatial reference system allows one to estimate the spatial variability of each cytoarchitectonically defined region with respect to this reference system. In future, the transfer of in vivo structural and functional data into the same spatial reference system will enable accurate comparisons of cytoarchitectonic maps of the primary auditory cortex with activation centers as established with functional imaging procedures.

Hemispheric shape of European and Japanese brains: 3-D MRI analysis of intersubject variability, ethnical, and gender differences.

Hemispheric shape is studied using magnetic resonance imaging and 3-D reconstructions in right-handed, male and female, European and Japanese subjects. Japanese hemispheres are relatively shorter, but wider than European hemispheres. Regions of maximal intersubject variability in hemispheric shape are present in the occipital and temporal lobes in each sample. Deviations from this general pattern are found in the (i) right inferior parietal lobule (European hemispheres are more variable than Japanese), (ii) lower third of the pre- and postcentral gyri (female Japanese hemispheres are less variable than the other samples), (iii) right inferior frontal gyrus (male European hemispheres are more variable than the other samples), and (iv) polar part of the frontal lobe (female European hemispheres are less variable than the other samples). The distribution of intersubject variability between the hemispheres is less asymmetric in female than male brains. Male Japanese hemispheres are shorter but wider than female Japanese hemispheres, whereas European hemispheres show the inverse gender relations. These results demonstrate that hemispheric shape shows a considerable intersubject variability, which is not randomly distributed over the cortical surface but displays distinct regions of higher variability. Despite this intersubject variability significant interethnic- and gender-related differences in hemispheric shape are present, which may be relevant if individual brains have to be warped to a single or mean reference brain or realistic brain models are to be constructed.

The effect of verbal feedback on motor learning--a PET study. Positron emission tomography.

The purpose of this study was to investigate brain mechanisms underlying feedback effects on motor learning. We measured human brain activity using positron emission tomography (PET) during length-of-line drawing tasks in the presence or absence of verbal feedback, i.e., information on the precision of motor performance. The average error in responses was significantly lower and the percentage of correct responses was significantly higher in the case of tasks with feedback than those in the absence of feedback. The contralateral sensorimotor, premotor, supplementary motor, the right prefrontal, bilateral parietal and temporal, and anterior cingulate cortices, and the left basal ganglia were activated during all the line-drawing tasks. The right lateral prefrontal and occipital cortices and the left basal ganglia exhibited marked increase in activity after learning. The right inferior parietal and the anterior cingulate cortices were activated in the presence of feedback which provided information on how the subjects should correct their performances. The results indicate that these brain areas may play an important role in representing knowledge of results during motor learning and that appropriate feedback may facilitate motor learning.

A stereological approach to human cortical architecture: identification and delineation of cortical areas.

Stereology offers a variety of procedures to analyze quantitatively the regional and laminar organization in cytoarchitectonically defined areas of the human cerebral cortex. Conventional anatomical atlases are of little help in localizing specific cortical areas, since most of them are based on a single brain and use highly observer-dependent criteria for the delineation of cortical areas. In consequence, numerous cortical maps exist which greatly differ with respect to number, position, size and extent of cortical areas. We describe a novel algorithm-based procedure for the delineation of cortical areas, which exploits the automated estimation of volume densities of cortical cell bodies. Spatial sampling of the laminar pattern is performed with density profiles, followed by multivariate analysis of the profiles' shape, which locates the cytoarchitectonic borders between neighboring cortical areas at sites where the laminar pattern changes significantly. The borders are then mapped to a human brain atlas system comprising tools for three dimensional reconstruction, visualization and morphometric analysis. A sample of brains with labeled cortical areas is warped into the reference brain of the atlas system in order to generate a population map of the cortical areas, which describes the intersubject variability in spatial conformation of cortical areas. These population maps provide a novel tool for the interpretation of images obtained with functional imaging techniques.

Functional mapping of human brain in olfactory processing: a PET study.

This study describes the functional anatomy of olfactory and visual naming and matching in humans, using positron emission tomography (PET). One baseline control task without olfactory or visual stimulation, one control task with simple olfactory and visual stimulation without cognition, one set of olfactory and visual naming tasks, and one set of olfactory and visual matching tasks were administered to eight normal volunteers. In the olfactory naming task (ON), odors from familiar items, associated with some verbal label, were to be named. Hence, it required long-term olfactory memory retrieval for stimulus recognition. The olfactory matching task (OM) involved differentiating a recently encoded unfamiliar odor from a sequentially presented group of unfamiliar odors. This required short-term olfactory memory retrieval for stimulus differentiation. The simple olfactory and visual stimulation resulted in activation of the left orbitofrontal region, the right piriform cortex, and the bilateral occipital cortex. During olfactory naming, activation was detected in the left cuneus, the right anterior cingulate gyrus, the left insula, and the cerebellum bilaterally. It appears that the effort to identify the origin of an odor involved semantic analysis and some degree of mental imagery. During olfactory matching, activation was observed in the left cuneus and the cerebellum bilaterally. This identified the brain areas activated during differentiation of one unlabeled odor from the others. In cross-task analysis, the region found to be specific for olfactory naming was the left cuneus. Our results show definite recruitment of the visual cortex in ON and OM tasks, most likely related to imagery component of these tasks. The cerebellar role in cognitive tasks has been recognized, but this is the first PET study that suggests that the human cerebellum may have a role in cognitive olfactory processing as well.

Functional delineation of the human occipito-temporal areas related to face and scene processing. A PET study.

By measuring regional cerebral blood flow using PET, we delineated the roles of the occipito-temporal regions activated by faces and scenes. We asked right-handed normal subjects to perform three tasks using facial images as visual stimuli: in the face familiar/unfamiliar discrimination (FF) task, they discriminated the faces of their friends and associates from unfamiliar ones; in the face direction discrimination (FD) task, they discriminated the direction of each unfamiliar face; in the dot location discrimination (DL) task, they discriminated the location of a red dot on a scrambled face. The activity in each task was compared with that in the control fixation (CF) task, in which they fixated on the centre of a display without visual stimuli. The DL task activated the occipital cortices and posterior fusiform gyri bilaterally. During the FD task, the activation extended anteriorly in the right fusiform gyrus and laterally to the right inferior temporal cortex. The FF task further activated the right temporal pole. To examine whether the activation due to faces was face-specific, we used a scene familiar/unfamiliar discrimination (SF) task, in which the subjects discriminated familiar scenes from unfamiliar ones. Our results suggest that (i) the occipital cortices and posterior fusiform gyri non-selectively respond to faces, scrambled faces and scenes, and are involved mainly in the extraction of physical features of complex visual images; (ii) the right inferior temporal/fusiform gyrus responds selectively to faces but not to non-face stimuli and is involved in the visual processing related to face perception, whereas the bilateral parahippocampal gyri and parieto-occipital junctions respond selectively to scenes and are involved in processing related to scene perception; and (iii) the right temporal pole is activated during the discrimination of familiar faces and scenes from unfamiliar ones, and is probably involved in the recognition of familiar objects.

Areas 3a, 3b, and 1 of human primary somatosensory cortex. Part 2. Spatial normalization to standard anatomical space.

Interindividual topographical variability of cytoarchitectonically defined somatosensory areas 3a, 3b, and 1 was analyzed in the standard anatomical format of a computerized brain atlas. T1-weighted magnetic resonance images were obtained from 10 postmortem brains. The brains were serially sectioned at 20 mcm, sections were stained for cell bodies, and areas 3a, 3b, and 1 were defined with an observer-independent cytoarchitectonic technique. After correction of the sections for deformations due to histological processing, the 3-D reconstructed histological volumes of the individual brains and the volume representations of the cytoarchitectonic areas were adapted to the reference brain of a computerized atlas. Corresponding areas were superimposed in the 3-D space of the reference brain. These population maps describe, for each voxel, how many brains have a representation of one particular cytoarchitectonic area. Each area's extent is very variable across different brains, but representations of areas 3a, 3b, and 1 in >/=50% of the brains were found in the fundus of the central sulcus, its caudal bank, and on the crown of the postcentral gyrus, respectively. Volumes of interest (VOIs) were defined for each area in which >/=50% of the brains have a representation of that area. Despite close spatial relationship of areas 3a, 3b, and 1 in the postcentral gyrus, the three VOIs overlap by <1% of their volumes. Functional imaging data can now be brought into the same standard anatomical format, and changes in regional cerebral blood flow can be calculated in VOIs of areas 3a, 3b, and 1, which are derived from genuine cytoarchitectonic data.

Correlation between human personality and neural activity in cerebral cortex.

Personality traits are a variance of behavioral patterns among individuals and may reflect a variance of brain activity, but their neurobiological explanation is still a matter of debate. Cloninger proposed three dimensions of personality traits, each of which has strong correlation with activity in a specific central monoaminergic system. Although this theory has been supported by physiological and genetic studies, it is still unclear how these personality parameters are correlated with the activity of the cortical networks which control human behavior. Here we measured the regional cerebral blood flow (rCBF) at rest in 30 normal volunteers who completed the personality inventory of Cloninger. Voxel-by-voxel analysis was employed to identify cortical regions where the rCBF showed significant correlation with any of the three personality parameters. Statistically significant correlation was observed in several paralimbic and neocortical regions and was consistent with the assumed monoaminergic influence on neural activity and the distribution of its projections, in each personality dimension. The results suggest that activity in a variety of cortical regions is associated with human personality traits and lend support to Cloninger's theory concerning central monoaminergic influence on human personality traits.

Brodmann's areas 17 and 18 brought into stereotaxic space-where and how variable?

Studies on structural-functional associations in the visual system require precise information on the location and variability of Brodmann's areas 17 and 18. Usually, these studies are based on the Talairach atlas, which does not rely on cytoarchitectonic observations, but on comparisons of macroscopic features in the Talairach brain and Brodmann's drawing. In addition, in this atlas are found only the approximate positions of cytoarchitectonic areas and not the exact borders. We have cytoarchitectonically mapped both areas in 10 human brains and marked their borders in corresponding computerized images. Borders were defined on the basis of quantitative cytoarchitecture and multivariate statistics. In addition to borders of areas 17 and 18, subparcellations within both areas were found. The cytoarchitectonically defined areas were 3-D reconstructed and transferred into the stereotaxic space of the standard reference brain. Surface rendering of the brains revealed high individual variability in size and shape of the areas and in the relationship to the free surface and sulci. Ranges and centers of gravity of both areas were calculated in Talairach coordinates. The positions of areas 17 and 18 in the stereotaxic space differed between the hemispheres. Both areas reached significantly more caudal and medial positions on the left than on the right. Probability maps were created in which the degree of overlap in each stereotaxic position was quantified. These maps of areas 17 and 18 are the first of their kind and contain precise stereotaxic information on both interhemispheric and interindividual differences.

Broca's region subserves imagery of motion: a combined cytoarchitectonic and fMRI study.

Broca's region in the dominant cerebral hemisphere is known to mediate the production of language but also contributes to comprehension. Here, we report the differential participation of Broca's region in imagery of motion in humans. Healthy volunteers were studied with functional magnetic resonance imaging (fMRI) while they imagined movement trajectories following different instructions. Imagery of right-hand finger movements induced a cortical activation pattern including dorsal and ventral portions of the premotor cortex, frontal medial wall areas, and cortical areas lining the intraparietal sulcus in both cerebral hemispheres. Imagery of movement observation and of a moving target specifically activated the opercular portion of the inferior frontal cortex. A left-hemispheric dominance was found for egocentric movements and a right-hemispheric dominance for movement characteristics in space. To precisely localize these inferior frontal activations, the fMRI data were coregistered with cytoarchitectonic maps of Broca's areas 44 and 45 in a common reference space. It was found that the activation areas in the opercular portion of the inferior frontal cortex were localized to area 44 of Broca's region. These activations of area 44 can be interpreted to possibly demonstrate the location of the human analogue to the so-called mirror neurones found in inferior frontal cortex of nonhuman primates. We suggest that area 44 mediates higher-order forelimb movement control resembling the neuronal mechanisms subserving speech.

Mapping of histologically identified long fiber tracts in human cerebral hemispheres to the MRI volume of a reference brain: position and spatial variability of the optic radiation.

The interpretation of the anatomical basis of functional deficits after subcortical infarcts could be considerably improved, if the precise topography and interindividual variability in size and course of long fiber tracts in adult human cerebral hemispheres were available in a spatial reference system. We therefore developed a method enabling the mapping of long fiber tracts to the volume of a standard reference brain. The examined fiber tracts were identified in myelin-stained histological serial sections of 10 human brains. The reference brain is a 3-D reconstruction of in vivo obtained magnetic resonance images (MRIs). The warping of histological volumes with the labeled fiber tracts to the reference brain by means of linear and nonlinear transformation procedures results in population maps that demonstrate the interindividual variability in position, size, and course of fiber tracts. In this paper, we present population maps of the optic radiation and the lateral geniculate body as a first example of this mapping strategy. Both structures present a considerable interindividual variability. Furthermore, voxel-based morphometry shows significant side differences with larger volumes of both structures in the left hemisphere than in the right hemisphere. A more than twofold variability of size in the interhemispheric extension of the optic radiation and the lateral geniculate body is found even after normalization of absolute brain size. Our observations demonstrate that the present approach based on population maps of fiber tracts and nuclei can improve the anatomical localization and interpretation of brain lesions visible in MRIs at the level of microstructurally identified architectonical units.

Three-dimensional linear and nonlinear transformations: an integration of light microscopical and MRI data.

The registration of image volumes derived from different imaging modalities such as MRI, PET, SPECT, and CT has been described in numerous studies in which functional and morphological data are combined on the basis of macrostructural information. However, the exact topography of architectural details is defined by microstructural information derived from histological sections. Therefore, a technique is developed for integrating micro- and macrostructural information based on 1) a three-dimensional reconstruction of the histological volume which accounts for linear and nonlinear histological deformations, and 2) a two-step procedure which transforms these volumes to a reference coordinate system. The two-step procedure uses an extended principal axes transformation (PAT) generalized to affine transformations and a fast, automated full-multigrid method (FMG) for determining high-dimensional three-dimensional nonlinear deformations in order to account for differences in the morphology of individuals. With this technique, it is possible to define upwards of 1,000 times the resolution of approximately 1 mm in MRI, making possible the identification of geometric and texture features of microscopically defined brain structures.