The frontal pole has more expanded than any other part in the human brain as compared to our ancestors. It plays an important role for specifically human behavior and cognitive abilities, e.g. action ...selection (Kovach et al., 2012). Evidence about divergent functions of its medial and lateral part has been provided, both in the healthy brain and in psychiatric disorders. The anatomical correlates of such functional segregation, however, are still unknown due to a lack of stereotaxic, microstructural maps obtained in a representative sample of brains. Here we show that the human frontopolar cortex consists of two cytoarchitectonically and functionally distinct areas: lateral frontopolar area 1 (Fp1) and medial frontopolar area 2 (Fp2). Based on observer-independent mapping in serial, cell-body stained sections of 10 brains, three-dimensional, probabilistic maps of areas Fp1 and Fp2 were created. They show, for each position of the reference space, the probability with which each area was found in a particular voxel. Applying these maps as seed regions for a meta-analysis revealed that Fp1 and Fp2 differentially contribute to functional networks: Fp1 was involved in cognition, working memory and perception, whereas Fp2 was part of brain networks underlying affective processing and social cognition. The present study thus disclosed cortical correlates of a functional segregation of the human frontopolar cortex. The probabilistic maps provide a sound anatomical basis for interpreting neuroimaging data in the living human brain, and open new perspectives for analyzing structure–function relationships in the prefrontal cortex. The new data will also serve as a starting point for further comparative studies between human and non-human primate brains. This allows finding similarities and differences in the organizational principles of the frontal lobe during evolution as neurobiological basis for our behavior and cognitive abilities.
•The human frontopolar cortex consists of two cytoarchitectonically distinct areas.•3D probabilistic maps of frontopolar area 1 and 2 (Fp1,Fp2) were created.•Quantitative inference showed involvement in cognition (Fp1) and emotion (Fp2).•Significant difference in task-based functional connectivity between Fp1 and Fp2.
The present paper reviews that macroanatomical landmarks are problematic for a reliable and sufficiently precise localization of clusters of activation obtained by functional imaging because sulcal ...and gyral patterns are extremely variable and macroanatomical landmarks do not match (in nearly all cases) architectonically defined borders. It argues that cytoarchitectonic probabilistic maps currently offer the most precise tool for the localization of brain functions as obtained from functional imaging studies. Finally, it provides some examples that cytoarchitecture is more than localization with respect to a particular brain region because it reflects the inner organization of cortical areas and, furthermore, functional principles of the brain.
The basal forebrain contains several interdigitating anatomical structures, including the diagonal band of Broca, the basal nucleus of Meynert, the ventral striatum, and also cell groups underneath ...the globus pallidus that bridge the centromedial amygdala to the bed nucleus of the stria terminalis. Among the cell populations, the magnocellular, cholinergic corticopetal projection neurons have received particular attention due to their loss in Alzheimer's disease. In MRI images, the precise delineation of these structures is difficult due to limited spatial resolution and contrast. Here, using microscopic delineations in ten human postmortem brains, we present stereotaxic probabilistic maps of the basal forebrain areas containing the magnocellular cell groups. Cytoarchitectonic mapping was performed in silver stained histological serial sections. The positions and the extent of the magnocellular cell groups within the septum (Ch1–2), the horizontal limb of the diagonal band (Ch3), and in the sublenticular part of the basal forebrain (Ch4) were traced in high-resolution digitized histological sections, 3D reconstructed, and warped to the reference space of the MNI single subject brain. The superposition of the cytoarchitectonic maps in the MNI brain shows the intersubject variability of the various Ch compartments and their stereotaxic position relative to other brain structures. Both the right and left Ch4 regions showed significantly smaller volumes when age was considered as a covariate. Probabilistic maps of compartments of the basal forebrain magnocellular system are now available as an open source reference for correlation with fMRI, PET, and structural MRI data of the living human brain.
Cholinergic neurons of the medial forebrain are considered important contributors to brain plasticity and neuromodulation. A reduction of cholinergic innervation can lead to pathophysiological ...changes of neurotransmission and is observed in Alzheimer's disease. Here we report on six patients with mild to moderate Alzheimer's disease (AD) treated with bilateral low-frequency deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM). During a four-week double-blind sham-controlled phase and a subsequent 11-month follow-up open label period, clinical outcome was assessed by neuropsychological examination using the Alzheimer's Disease Assessment Scale-cognitive subscale as the primary outcome measure. Electroencephalography and (18)F-fluoro-desoxyglucose positron emission tomography were, besides others, secondary endpoints. On the basis of stable or improved primary outcome parameters twelve months after surgery, four of the six patients were considered responders. No severe or non-transitional side effects related to the stimulation were observed. Taking into account all limitations of a pilot study, we conclude that DBS of the NBM is both technically feasible and well tolerated.
The human cerebral cortex is made up of a mosaic of structural areas, frequently referred to as Brodmann areas (BAs). Despite the widespread use of cortical folding patterns to perform ad hoc ...estimations of the locations of the BAs, little is understood regarding 1) how variable the position of a given BA is with respect to the folds, 2) whether the location of some BAs is more variable than others, and 3) whether the variability is related to the level of a BA in a putative cortical hierarchy. We use whole-brain histology of 10 postmortem human brains and surface-based analysis to test how well the folds predict the locations of the BAs. We show that higher order cortical areas exhibit more variability than primary and secondary areas and that the folds are much better predictors of the BAs than had been previously thought. These results further highlight the significance of cortical folding patterns and suggest a common mechanism for the development of the folds and the cytoarchitectonic fields.
Probabilistic maps of neocortical areas and subcortical fiber tracts, warped to a common reference brain, have been published using microscopic architectonic parcellations in ten human postmortem ...brains. The maps have been successfully applied as topographical references for the anatomical localization of activations observed in functional imaging studies. Here, for the first time, we present stereotaxic, probabilistic maps of the hippocampus, the amygdala and the entorhinal cortex and some of their subdivisions. Cytoarchitectonic mapping was performed in serial, cell-body stained histological sections. The positions and the extent of cytoarchitectonically defined structures were traced in digitized histological sections, 3-D reconstructed and warped to the reference space of the MNI single subject brain using both linear and non-linear elastic tools of alignment. The probability maps and volumes of all structures were calculated. The precise localization of the borders of the mapped regions cannot be predicted consistently by macroanatomical landmarks. Many borders, e.g. between the subiculum and entorhinal cortex, subiculum and Cornu ammonis, and amygdala and hippocampus, do not match sulcal landmarks such as the bottom of a sulcus. Only microscopic observation enables the precise localization of the borders of these brain regions. The superposition of the cytoarchitectonic maps in the common spatial reference system shows a considerably lower degree of intersubject variability in size and position of the allocortical structures and nuclei than the previously delineated neocortical areas. For the first time, the present observations provide cytoarchitectonically verified maps of the human amygdala, hippocampus and entorhinal cortex, which take into account the stereotaxic position of the brain structures as well as intersubject variability. We believe that these maps are efficient tools for the precise microstructural localization of fMRI, PET and anatomical MR data, both in healthy and pathologically altered brains.
Recently, 8 areas (5Ci, 5M, 5L, 7PC, 7A, 7P, 7M, hIP3) in the human superior parietal cortex (SPC) were delineated in 10 postmortem brains using observer-independent cytoarchitectonic analysis. Here ...we present 3D probabilistic maps of these areas, quantifying the interindividual overlap for each voxel in stereotaxic reference space, and a maximum probability map, providing a contiguous parcellation. For all areas, we determined probabilities of mutual borders, calculated stereotaxic centers of gravity, and estimated volumes. A basic pattern of areas and borders was observed, which showed, however, intersubject variations and a significant interhemispheric asymmetry (7P, 7M) that may be functionally relevant. There was a trend toward higher intersubject anatomical variability in lateral compared with medial areas. For several areas (5M, 7PC, 7A, 7P), variability was significantly higher in the left hemisphere and/or in men, whereas for areas 5Ci and 5M there was a hemisphere-by-gender interaction. Differences in anatomical variability could bias group analyses in functional imaging studies by reducing sensitivity for activations of entities with high variability. The probabilistic maps provide an objective anatomical reference and account for the structural variability of the human brain. Integrated into functional imaging experiments, they can improve structure–function investigations of the human SPC.
The human posterior insula was shown to respond to a wide variety of stimulation paradigms (e.g. pain, somatosensory, or auditory processing) in functional imaging experiments. Although various ...anatomical maps of this region have been published over the last century, these schemes show variable results. Moreover, none can directly be integrated with functional imaging data. Hence, our current knowledge about the structure-function relationships in this region remains limited. We therefore remapped the posterior part of the human insular cortex in 10 postmortem brains using an observer-independent approach. This analysis revealed the existence of 3 cytoarchitectonically distinct areas in the posterior insula. The examined brains were then 3D reconstructed and spatially normalized to the Montreal Neurological Institute single-subject template. Probabilistic maps for each area were calculated by superimposing the individual delineations, and a cytoarchitectonic summary map was computed to chart the regional architectonic organization. These maps can be used to identify the anatomical correlates of functional activations observed in neuroimaging studies and to understand the microstructural correlates of the functional segregation of the human posterior insula.
We used functional magnetic resonance imaging (fMRI) and cytoarchitectonic probability maps to investigate the responsiveness of individual areas in the human primary and secondary somatosensory ...cortices to hand, face, or trunk stimulation of either body-side. A Bayesian modeling approach to quantify the probability of ipsilateral activations revealed that areas OP 1, OP 4, and OP 3 of the SII cortex as well as the trunk and face representations within all SI subareas (areas 3b, 1, and 2) show robust bilateral responses to unilateral stimulation. Such bilateral response properties are in good agreement with the transcallosal projections demonstrated for these areas in nonhuman primates and other mammals. In contrast, the SI hand region showed a different pattern. Whereas ipsilateral areas 3b and 1 were deactivated by tactile hand stimulation, particularly on the left, there was strong evidence for ipsilateral processing of information from the right hand in area 2. These results demonstrate not only the behavioral importance of the hand representation, but also suggest that area 2 may have particularly evolved to form the cortical substrate of these specialized demands, in line with recent studies on cortical evolution hypothesizing that area 2 has developed with increasing manual abilities in anthropoid primates featuring opposable thumbs.
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