Harry B.M. Uylings

Broca's region revisited: cytoarchitecture and intersubject variability.

The sizes of Brodmanns areas 44 and 45 (Brocas speech region) and their extent in relation to macroscopic landmarks and surrounding areas differ considerably among the available cytoarchitectonic maps. Such variability may be due to intersubject differences in anatomy, observer‐dependent discrepancies in cytoarchitectonic mapping, or both. Because a reliable definition of cytoarchitectonic borders is important for interpreting functional imaging data, we mapped areas 44 and 45 by means of an observer‐independent technique. In 10 human brains, the laminar distributions of cell densities were measured vertical to the cortical surface in serial coronal sections stained for perikarya. Thousands of density profiles were obtained. Cytoarchitectonic borders were defined as statistically significant changes in laminar patterns. The analysis of the three‐dimensional reconstructed brains and the two areas showed that cytoarchitectonic borders did not consistently coincide with sulcal contours. Therefore, macroscopic features are not reliable landmarks of cytoarchitectonic borders. Intersubject variability in the cytoarchitecture of areas 44 and 45 was significantly greater than cytoarchitectonic differences between these areas in individual brains. Although the volumes of area 44 differed across subjects by up to a factor of 10, area 44 but not area 45 was left‐over‐right asymmetrical in all brains. All five male but only three of five female brains had significantly higher cell densities on the left than on the right side. Such hemispheric and gender differences were not detected in area 45. These morphologic asymmetries of area 44 provide a putative correlate of the functional lateralization of speech production. J. Comp. Neurol. 412:319–341, 1999.

Cerebral blood flow changes during script-driven imagery in police officers with posttraumatic stress disorder.

BACKGROUND Functional brain imaging studies in posttraumatic stress disorder (PTSD) have focused mostly on war or sexual abuse victims, many of whom also had comorbid disorders. The aim of this study was to examine the neuronal circuitry underlying responses to script-driven imagery in traumatized police officers with and without PTSD and with low comorbidity rates. METHODS In a case-matched control study, 30 traumatized police officers with and without PTSD underwent clinical assessment and (99m)technetium-hexa-methyl-propylene-amine-oxime single photon emission computed tomography scanning with neutral and trauma scripts. Statistical parametric mapping was applied to analyze changes in regional cerebral blood flow. RESULTS The main findings were significantly less activation in the medial frontal gyrus and more activation in the right cuneus in the PTSD group relative to the trauma-exposed control group in reaction to trauma versus neutral scripts. Within the PTSD group, subjects showed less activation in the superior temporal gyrus, left lentiform nucleus, left middle frontal gyrus, and left inferior frontal gyrus in reaction to trauma scripts. CONCLUSIONS We confirmed previous findings of dysfunction of the medial frontal gyrus in PTSD in a new population with low comorbidity rates. Other alterations were found in certain brain structures involved in emotional, memory, linguistic, visuospatial, and motor processing.

Consequences of large interindividual variability for human brain atlases: converging macroscopical imaging and microscopical neuroanatomy

In human brain imaging studies, it is common practice to use the Talairach stereotaxic reference system for signifying the convergence of brain function and structure. In nearly all neuroimaging reports, the studied cortical areas are specified further with a Brodmann Area (BA) number. This specification is based upon macroscopic extrapolation from Brodmann’s projection maps into the Talairach atlas rather than upon a real microscopic cytoarchitectonic study. In this review we argue that such a specification of Brodmann area(s) via the Talairach atlas is not appropriate. Cytoarchitectonic studies reviewed in this paper show large interindividual differences in 3-D location of primary sensory cortical areas (visual cortex) as well as heteromodal associational areas (prefrontal cortical areas), even after correction for differences in brain size and shape. Thus, the simple use of Brodmann cortical areas derived from the Talairach atlas can lead to erroneous results in the specification of pertinent BA. This in turn can further lead to wrong hypotheses on brain system(s) involved in normal functions or in specific brain disorders. In addition, we will briefly discuss the different ‘Brodmann’ nomenclatures which are in use for the cerebral cortex.

NATURAL VARIABILITY IN THE NUMBER OF DENDRITIC SEGMENTS: MODEL-BASED INFERENCES ABOUT BRANCHING DURING NEURITE OUTGROWTH

A study was made of the possible basis for naturally occurring variations in the number of segments in individual dendritic trees. Distributions of the number of terminal segments have been studied in dendrites from rat, cat, and frog motoneurons, basal dendrites from rat visual cortex pyramidal and non‐pyramidal neurons, in rat cerebellar Purkinje cell dendritic trees, and in human hippocampal dentate granule cells. By means of a mathematical model for dendritic branching, it was shown that the variation in the number of dendritic segments can be accounted for by assuming that new branches during neurite outgrowth are formed randomly at terminal segments. The observed terminal segment number distributions could be closely approximated by additionally assuming that branching probabilities decline with increasing number of terminal segments in growing dendrites. The pyramidal neuron group differed significantly from the other neuron groups in such a way as to suggest that this decline is stronger than in the dendrites of other types of neurons. By using literature data on the mean number of terminal segments in rat cerebellar Purkinje cells, measured at different times during early development, an estimate could be obtained of the time‐course of the branching probabilities. The branching probability of a terminal segment was found to be in the order of 0.002 per hour in the first 4 weeks postnatal with a 5‐fold transient increase in the second week. J. Comp. Neurol. 387:325–340, 1997.

LEFT-RIGHT ASYMMETRY IN VOLUME AND NUMBER OF NEURONS IN ADULT BROCA'S AREA

Total neuron number in, and volume of, Brodmann areas (BA) 44 and 45 (Brocas area) were studied in Nissl-stained sections from the left and right hemispheres of five adult men and five adult women. The volume of BA 44 was greater in the left hemisphere than in the right in all ten cases, although asymmetry was only significant for the subgroup of male subjects. For six of the ten subjects (including all females), the volume of BA 45 was greater in the left hemisphere than the right. This asymmetry was significant only for the women. A significant left-over-right asymmetry has been found in total neuron number in male BA 44. Although the total number of neurons in left BA 45 was larger in all five female subjects, this asymmetry did not reach significant difference. In the male subjects no significant asymmetry difference in total neuron number was found in BA 45 either. There was no significant hemispheric asymmetry or gender interaction for neuronal number density, either in BA 44 or 45. This study is the first quantitative study of total number of neurons in BA 44 and 45 in adult subjects, and demonstrates that both the volume and the total neuron number of BA 44 and 45 on the left are generally greater than that of the right hemisphere, with the possible exception of the male BA 45. In addition, it shows that the inter-individual variability was also very large (more than twofold) in the numerical values of all variables.

The need for integrating neuronal morphology databases and computational environments in exploring neuronal structure and function.

Neurons connect to each other through a myriad of dendritic and axonal arborisations. Dendritic structures provide the substrate for integration of postsynaptic potentials and control of action potential generation. Axonal structures provide the substrate for action potential dissemination and signalling to target neurons. The morphological complexity of dendritic arborisations is assumed to play a critical role in the transformation of spatio-temporal patterns of postsynaptic potentials into time-structured series of action potentials. Although these transformations lie at the basis of information processing in the brain, it is still far from understood how their details are influenced by dendritic shape. To facilitate research in this area, it is necessary that data on both the morphology and electrical properties of neurons, as well as computational tools for analysis, become available in an integrated way. This requires a combined effort from the fields of informatics and neurosciences (together called neuroinformatics) in order to create data acquisition, databasing and computational tools. Focusing on neuronal morphology, this chapter will give a brief review of the current neuroinformatics developments in both reconstruction techniques, morphological quantification, modeling of morphological complexity, modeling of function and the need for databasing neuronal morphologies. Additionally, one of the dendritic modeling approaches is described in more detail in the Appendix.

Statistical Analysis of Neuronal Populations

The neuronal tree alters during development and aging and in several cases during disease and experimental treatment (e.g., Mrzljak et al., 1988; Coleman and Flood, 1987; De Ruiter and Uylings, 1987). In quantitative assessment, metric and topological analysis offer us important tools for estimating the type and size of these alterations. Topological analysis, dealing with the number of branchings and connectivity pattern of segments but not the physical size of individual neurons, has been dealt with in Chapter 10. Metric analysis, referring to neuronal size of individual neurons, has been dealt with in Chapter 9 of this book. In this chapter we discuss metric analysis further, with special attention to populations of neurons, and consider the variation between and within animals to estimate the number of animals and the number of neurons required for a statistical comparison.

Branching rates and growth functions in the outgrowth of dendritic branching patterns

The outgrowth of dendritic branching patterns proceeds by neurite elongation and branching. These actions are supported by growth cones, specialized dynamic structures at the tips of outgrowing neurites, in response to a multitude of intracellular and extracellular signals and mechanisms. Branching rates of growth cones and their temporal patterns thus reflect the extent and changes in these responses. The present study outlines a model framework to relate branching rates of individual growth cones with the growth rate of the entire dendritic tree. The branching rate of an individual growth cone is assumed to depend on the total number of growth cones at any given moment (representing competition between growth cones), on its position along the dendrite, and on a baseline component representing all other factors. Four different strategies are discussed for determining quantitatively these components from experimental data. The methods are applied in the analysis of dendritic trees of Wistar rat multipolar non-pyramidal neurons, quantitatively reconstructed at several developmental stages (Parnavelas J G and Uylings H B M 1980 Brain Res. 193 373–82, Uylings H B M, Parnavelas J G, Walg H and Veltman W A M 1980 Mikroskopie 37 220–4). It is shown that the baseline branching rate is a rapidly decreasing function of time, indicating the largest baseline drive for branching in the early days of outgrowth.

Topological Analysis of Individual Neurons

What is topology? Topology is the study of geometric surfaces with concern only for their mathematical form but not their physical size. A topologist thinks of structures as formed from rubber sheets that can be stretched at will, and as long as no holes are poked in them, the properties of the structure do not change. Carried to a humorous extreme as Fig. 10-1 indicates, a coffee cup and a donut are topologically equivalent structures, for they both have the same form, a surface with one hole.

Modeling dendritic morphological complexity of deep layer cat superior colliculus neurons

Abstract Dendritic complexity of deep layer cat superior colliculus neurons has been studied by means of a stochastic model for dendritic outgrowth with randomly branching and elongating neurites. Branching probabilities are assumed to depend on the position and the number of segments in the growing tree. It is demonstrated that the shape properties of model generated dendrites conform closely to those of the observed trees. These findings make plausible that (i) dendritic development proceeds following a first phase of elongation and branching, and a second phase of elongation only, and (ii) newly formed segments after a branching event have a short initial length.