Whole-brain neuroimaging studies have demonstrated regional variations in function within human cingulate cortex. At the same time, regional variations in cingulate anatomical connections have been found in animal models. It has, however, been difficult to estimate the relationship between connectivity and function throughout the whole cingulate cortex within the human brain. In this study, magnetic resonance diffusion tractography was used to investigate cingulate probabilistic connectivity in the human brain with two approaches. First, an algorithm was used to search for regional variations in the probabilistic connectivity profiles of all cingulate cortex voxels with the whole of the rest of the brain. Nine subregions with distinctive connectivity profiles were identified. It was possible to characterize several distinct areas in the dorsal cingulate sulcal region. Several distinct regions were also found in subgenual and perigenual cortex. Second, the probabilities of connection between cingulate cortex and 11 predefined target regions of interest were calculated. Cingulate voxels with a high probability of connection with the different targets formed separate clusters within cingulate cortex. Distinct connectivity fingerprints characterized the likelihood of connections between the extracingulate target regions and the nine cingulate subregions. Last, a meta-analysis of 171 functional studies reporting cingulate activation was performed. Seven different cognitive conditions were selected and peak activation coordinates were plotted to create maps of functional localization within the cingulate cortex. Regional functional specialization was found to be related to regional differences in probabilistic anatomical connectivity.

Synaptogenesis in the ferret cerebral cortex was examined from the day of birth to adulthood with an antibody against synaptophysin at the light and electron microscopic levels. Due to the premature birth of ferrets, the generation of cells destined to the upper cortical layers and their subsequent migration to their final positions in the cortical plate are largely postnatal events. Throughout the newborn ferret cerebral cortex, a high amount of synaptophysin immunoreactivity was present within the marginal zone and subplate region. Staining was also conspicuous within the forming cortical plate. The typical layering pattern of synaptophysin immunoreactivity in the developing cortical plate correlated with the migration pattern of cortical neurons. The synaptic density was lowest directly below the marginal zone, where the youngest neurons just stopped their migration. Below this zone, the density of the synaptic staining increased gradually toward lower (and older) cortical plate layers. As the cortex expanded, the synaptophysin immunoreactivity pattern closely followed the expansion, suggesting that synapses were formed in a given layer shortly after the cells migrating to this layer reached their final position. As soon as cell migration had finished, the entire cortical plate contained dense synaptophysin immunoreactivity, in a pattern similar to that observed in the adult animal. During cortical development, a rostrocaudal and a laterodorsal gradient of synaptogenesis was observed. At any given time, rostral and lateral regions of the cerebral cortex were more advanced in their development than caudal and dorsal regions. Electron microscopic examination of synaptophysin immunoreactivity in the developing cerebral cortex of ferrets confirmed that labeling was solely associated with synaptic vesicles. These vesicles were typically, but not exclusively, confined to synaptic boutons. Especially around the end of the first postnatal week, long fiber profiles loaded with synaptic vesicles were occasionally detected. As some of these fibers also showed en passant synapses along their course, we concluded that synaptic vesicle labeling may be reliably used to study synaptogenesis at the light microscopic level. A systematic analysis of samples from postnatal days 0 and 7 corroborated this conclusion, showing that synaptic profile distribution completely matched the distribution of synaptophysin immunoreactivity seen in the light microscope. In conclusion, synaptogenesis begins as soon as migratory cells reach their final position in the cortical plate. As long as cell migration continues, synaptogenesis is under the constraints of neurogenesis, following its gradients.

Our data demonstrate high overall interest and frequent use of CAM in advanced breast cancer patients supporting a strong demand of breast cancer patients for complementary counseling and treatments additional to the established cancer therapies. It is indispensable to implement counseling and evidence-based complementary treatments into clinical routine of cancer centers and to adapt postgraduate medical education, respectively.