Reduced minicolumns in the frontal cortex of patients with autism.

Cell minicolumns were shown to be narrower in frontal regions in brains of autistic patients compared with controls. This was not found in primary visual cortex. Within the frontal cortex, dorsal and orbital regions displayed the greatest differences while the mesial region showed the least change. We also found that minicolumns in the brain of a 3-year-old autistic child were indistinguishable from those of the autistic adult in two of three frontal regions, in contrast to the control brains. This may have been due to the small size of the columns in the adult autistic brain rather than to an accelerated development. The presence of narrower minicolumns supports the theory that there is an abnormal increase in the number of ontogenetic column units produced in some regions of the autistic brain during corticoneurogenesis.

Rett syndrome as a minicolumnopathy.

OBJECTIVE: Rett syndrome is a progressive neurological disorder affecting primarily females. It is characterized by the early regression of acquired language, cognitive functions, social skills, and purposeful hand function. Patients with Rett syndrome are often misdiagnosed as autistic. Recent reports of minicolumnar abnormalities in the brains of autistic and Asperger's syndrome prompted us to search for similar pathology in Rett syndrome. MATERIAL: The patient population consisted of 5 Rett syndrome patients (mean age = 14.4 +/- 4.0 years) and 17 controls (mean age = 14.6 +/- 9.5 years). Tissue was celloidin embedded, sectioned at 35 um and Nissl stained. Images (100x) were taken from Brodmann's areas 9, 21, and 22 from layer III of the left hemisphere. METHOD: Columnar width measurements for these images were obtained with computerized image analysis using previously published algorithms. Each area was analyzed separately with univariate ANOVA, including diagnosis as a fixed factor and age (linear and quadratic terms), and sex as covariates. RESULTS: Diagnosis dependent effects were statistically significant only in area 21 (p = 0.009) even when taking into account a Bonferroni correction for the multiple comparisons. CONCLUSION: Both the regional nature of the changes as well as differences in mean cell spacing differentiates the abnormal minicolumnar morphometry of Rett syndrome from that of autism.

Quantitative comparison of radial cell columns in children with Down's syndrome and controls.

No one has examined the configuration of the minicolumns in Down's syndrome (DS) brains even though these are a basic functional unit of the cortex. In the present study, the authors used computerized imaging to examine minicolumns in the posterior superior temporal gyrus in both the brains of patients with DS and normal controls. They compared the brains of children aged 4 and 6 years with those of adults for both people with DS and the normal population. Columns in the brains of two DS children aged 4 and 6 years were almost the same size as those of the adults with DS. The neuropil space in the periphery of the columns was also considerably wider. In contrast, minicolumns in aged-matched control children were smaller, both relatively and absolutely, when compared to the mean size of adult columns. The size of the minicolumns in the normal children apparently corresponded to the overall brain size, whereas the large columns in children with DS appeared to be independent of brain size, at least in area Tpt. This seems to reflect a rapid ageing process that is striking when compared to normal controls. Columns in adults with DS were large and less cell dense, while brain volumes were significantly smaller than in controls. This combination suggests reduced neuronal complexity based on a decrease in processing units, which supports previous findings of decreased cell numbers and synaptic diminution in DS brains.

Lateralization of minicolumns in human planum temporale is absent in nonhuman primate cortex.

Gross analyses of large brain areas, as in MRI studies of macroanatomical structures, average subtle alterations in small regions, inadvertently missing significant anomalies. We developed a computerized imaging program to microscopically examine minicolumns and used it to study Nissl-stained slides of normal human, chimpanzee, and rhesus monkey brains in a region of the planum temporale. With this method, we measured the width of cell columns, the peripheral neuropil space, the spacing density of neurons within columns, and the Gray Level index per minicolumn. Only human brain tissue revealed robust asymmetry in two aspects of minicolumn morphology: wider columns and more neuropil space on the left side. This asymmetry was absent in chimpanzee and rhesus monkey brains.

Morphological differences between minicolumns in human and nonhuman primate cortex.

Our study performed a quantitative investigation of minicolumns in the planum temporale (PT) of human, chimpanzee, and rhesus monkey brains. This analysis distinguished minicolumns in the human cortex from those of the other nonhuman primates. Human cell columns are larger, contain more neuropil space, and pack more cells into the core area of the column than those of the other primates tested. Because the minicolumn is a basic anatomical and functional unit of the cortex, this strong evidence showed reorganization in this area of the human brain. The relationship between the minicolumn and cortical volume is also discussed.

Quantitative analysis of cell columns in the cerebral cortex.

We present a quantified imaging method that describes the cell column in mammalian cortex. The minicolumn is an ideal template with which to examine cortical organization because it is a basic unit of function, complete in itself, which interacts with adjacent and distance columns to form more complex levels of organization. The subtle details of columnar anatomy should reflect physiological changes that have occurred in evolution as well as those that might be caused by pathologies in the brain. In this semiautomatic method, images of Nissl-stained tissue are digitized or scanned into a computer imaging system. The software detects the presence of cell columns and describes details of their morphology and of the surrounding space. Columns are detected automatically on the basis of cell-poor and cell-rich areas using a Gaussian distribution. A line is fit to the cell centers by least squares analysis. The line becomes the center of the column from which the precise location of every cell can be measured. On this basis several algorithms describe the distribution of cells from the center line and in relation to the available surrounding space. Other algorithms use cluster analyses to determine the spatial orientation of every column.

Comparative lateralisation patterns in the language area of human, chimpanzee, and rhesus monkey brains.

Lateralised architectural differences in radial cell column structure were detected in the planum temporale of humans but were not found in homologous regions of ape or monkey brains. This study used a new computer imaging method to quantify the architecture of thousands of cortical minicolumns. A study of Lamina III in the left hemisphere of human brains revealed a wider separation between cell columns and more non-neuronal (empty) space within cell columns compared to the right hemisphere. This asymmetry was absent in the chimpanzee brains and weakly reversed in the rhesus monkey brains. The results imply an evolution towards more clearly defined columnar structures in the left hemisphere of human brains compared to those of monkeys.

The linear organization of cell columns in human and nonhuman anthropoid Tpt cortex.

Neurons in the cerebral cortex are organized horizontally into laminae and vertically into columns and modules. Little is known about the structural variation of neuronal organization in the vertical (pia to white matter) dimension. We describe here a new computer-assisted methodology that quantifies the linear arrangement of cells and shows how cortical columns in a homologous region differ by species and age. Perikarya in eulaminate temporal cortex, Tpt, were segmented from the background on the basis of their optical densities and sizes in human, rhesus (Macaca mulatta), and chimpanzee (Pantroglodytes) brains. Within each lamina, the two-dimensional arrays of neurons were divided into repetitive, objectively defined vertical clusters. Following this, ratios and indices quantified the displacement of perikaryal centroids from the central axis and from the center point in each cell cluster. The extremely linear and vertical arrangement of cells in the prelaminated fetal cortical plate served as the template to which the other arrays were compared. In all species, the linear arrangements of perikarya in lamina III, and to a lesser extent, in lamina V, closely resemble that of the early fetal template, whereas perikaryal arrangements in layers II and IV diverge from the template formation. Corroborating subjective visualization, each lamina had its own 'fingerprint'. As expected, cell density is less in the species with larger brains, with most of the differences in density coming from increased spacing between cellular columns rather than among the cells within columns. Not all aspects of perik-aryal organization alter when bigger brains are compared with smaller ones. Although chimpanzee brains are about four times bigger than those of rhesus monkeys and human brains are about three times larger than chimpanzee brains, absolute measures of cellular linearity in chimpanzees and rhesus monkeys resemble each other more closely than the same measures do in humans and chimpanzees. After accounting for differences in interval widths, the parameters of linearity sorted on the basis of brain weight in pyramidal cell layers III and V, but not in the stellate cell layers II and IV. Human perikarya have the widest horizontal dispersion and this displacement is most pronounced in layer II, least in layer III.

Cortical gyrification in the rhesus monkey: a test of the mechanical folding hypothesis.

A quantitative measure of the degree of cortical folding was used to test the mechanical hypothesis of cortical folding and to analyze structural properties of the rhesus monkey cortex. The rhesus monkey cortex has both its maximal degree of cortical folding and the largest ratios of supragranular laminae to the lower granular and infragranular layers in the caudal cortex, over the posterior parietal-anterior occipital regions. Low values for cortical folding and for the ratios of inner and outer cortical layers characterize frontal regions. Topographically intermediate regions are intermediate in both sets of values. Ratios of the amounts of white and gray matter have a topographic pattern that differs from those of cortical folding, suggesting that the sizes of subcortical axonal bundles are not directly associated with the degree of cortical folding. Whereas differences in mean degrees of cortical folding are correlated with brain weights among species of primates, the amount of folding is not associated with brain weight within the species.