Quantitative microscopic anatomy, illustrated by its potential role in furthering understanding of the processes of structuring the developing human cerebral cortex.

In this study, we searched for patterns in selected, quantitative microscopic features of the developing postnatal human cortex for 35 cytoarchitectural areas at eight age points from birth to 72 months. These data come from the largest extant survey of the microscopic features of the developing postnatal human cerebral cortex (JL Conel, 1939-67). In contrast to Jacobson's proposal that cortical surface area increases in proportion to brain weight, Conel's data show that surface area increases as brain weight2/3, with the maximal rate of increase in both brain weight and cortical surface area occurring from 1 to 3 months. We computed the numbers of cortical neurons per cortical layer under 1 mm2 of cortical surface (neurons/layer per mm2 column) and divided these values by the total neuron number/mm2 column. For all areas, these data show plateaux in most of the layers for periods of months to years, often preceded and followed by changes in their neuron number in a sinusoidal fashion. The age points of the maxima and minima of such laminar values differ across the 35 cortical areas, indicating that their sinusoids are phase-shifted with respect to each other. Ranking the six layers in each area at each age point by their neuron number/layer per mm2 column shows that, by 72 months, the first areas to receive thalamic auditory or visual input (primary sensory and unimodal association cortices) have the most neurons in layer 4 and in either layer 3 or 6. In contrast, by 72 months, other areas have the most neurons in layers 3 and 6, with the primary motor cortex reaching this ranking earlier than any other area. For temporal and parietal association areas, layers 2 (short cortico-cortical connections) and 4 (thalamo-cortical connections) have the most neurons from birth to 6 months, whereas layers 3 (long cortico-cortical connections) and 6 (cortico-thalamic connections) have the most neurons by 72 months. The quantitative, statistically non-random patterns demonstrated by our analyses suggest that hierarchical correlations between such structural changes and age-specific behavioral acquisitions exist during the first 72 months of postnatal development.