The human cerebral cortex is neither one nor many: neuronal distribution reveals two quantitatively different zones in the gray matter, three in the white matter, and explains local variations in cortical folding

Pedro F. M. Ribeiro,José M. Farfel,Bruno Mota,Wilson J. Filho,Lissa Ventura-Antunes,Mariana Gabi,Suzana Herculano-Houzel,Renata E. L. Ferretti-Rebustini,Lea T. Grinberg,Renata E. P. Leite

doi:10.3389/fnana.2013.00028

Abstract

The human prefrontal cortex has been considered different in several aspects and relatively enlarged compared to the rest of the cortical areas. Here we determine whether the white and gray matter of the prefrontal portion of the human cerebral cortex have similar or different cellular compositions relative to the rest of the cortical regions by applying the Isotropic Fractionator to analyze the distribution of neurons along the entire anteroposterior axis of the cortex, and its relationship with the degree of gyrification, number of neurons under the cortical surface, and other parameters. The prefrontal region shares with the remainder of the cerebral cortex (except for occipital cortex) the same relationship between cortical volume and number of neurons. In contrast, both occipital and prefrontal areas vary from other cortical areas in their connectivity through the white matter, with a systematic reduction of cortical connectivity through the white matter and an increase of the mean axon caliber along the anteroposterior axis. These two parameters explain local differences in the distribution of neurons underneath the cortical surface. We also show that local variations in cortical folding are neither a function of local numbers of neurons nor of cortical thickness, but correlate with properties of the white matter, and are best explained by the folding of the white matter surface. Our results suggest that the human cerebral cortex is divided in two zones (occipital and non-occipital) that differ in how neurons are distributed across their gray matter volume and in three zones (prefrontal, occipital, and non-occipital) that differ in how neurons are connected through the white matter. Thus, the human prefrontal cortex has the largest fraction of neuronal connectivity through the white matter and the smallest average axonal caliber in the white matter within the cortex, although its neuronal composition fits the pattern found for other, non-occipital areas.

Highlights

The notion that the human being is extraordinary, an exception to evolutionary rules that apply to other primates, has pervaded studies of the neuroanatomical bases of human cognition
We examine how these properties vary in the subcortical white matter along the AP axis in relationship to the distribution of neurons in the gray matter, test whether our model predicts the local variations in cortical folding along the human cerebral cortex
The present quantitative analysis of the cellular composition, volume, surface area, thickness and gyrification of the human cerebral cortex across its anteroposterior axis reveals that 42% of the variation in the parameters analysed is explained jointly by variations in numbers of neurons, other cells, volume and surface area of both the gray and white matter

Summary

Introduction

The notion that the human being is extraordinary, an exception to evolutionary rules that apply to other primates, has pervaded studies of the neuroanatomical bases of human cognition. While seemingly supportive of a particular enlargement of the prefrontal cortical white (but not gray) matter, these studies do not address how cortical volume relates to numbers of neurons in the gray matter, or of fibers in the white matter. Their usual interpretation assumes an even distribution of neurons across the cortical volume (Rockel et al, 1980), and a resulting direct relationship between cortical volume and numbers of neurons, such that cortical volume can be a valid proxy for numbers of neurons across cortical regions.

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Results

Conclusion