No relative expansion of the number of prefrontal neurons in primate and human evolution.

Human evolution is widely thought to have involved a particular expansion of prefrontal cortex. This popular notion has recently been challenged, although controversies remain. Here we show that the prefrontal region of both human and nonhuman primates holds about 8% of cortical neurons, with no clear difference across humans and other primates in the distribution of cortical neurons or white matter cells along the anteroposterior axis. Further, we find that the volumes of human prefrontal gray and white matter match the expected volumes for the number of neurons in the gray matter and for the number of other cells in the white matter compared with other primate species. These results indicate that prefrontal cortical expansion in human evolution happened along the same allometric trajectory as for other primate species, without modification of the distribution of neurons across its surface or of the volume of the underlying white matter. We thus propose that the most distinctive feature of the human prefrontal cortex is its absolute number of neurons, not its relative volume.

Greater addition of neurons to the olfactory bulb than to the cerebral cortex of eulipotyphlans but not rodents, afrotherians or primates.

The olfactory bulb is an evolutionarily old structure that antedates the appearance of a six-layered mammalian cerebral cortex. As such, the neuronal scaling rules that apply to scaling the mass of the olfactory bulb as a function of its number of neurons might be shared across mammalian groups, as we have found to be the case for the ensemble of non-cortical, non-cerebellar brain structures. Alternatively, the neuronal scaling rules that apply to the olfactory bulb might be distinct in those mammals that rely heavily on olfaction. The group previously referred to as Insectivora includes small mammals, some of which are now placed in Afrotheria, a base group in mammalian radiation, and others in Eulipotyphla, a group derived later, at the base of Laurasiatheria. Here we show that the neuronal scaling rules that apply to building the olfactory bulb differ across eulipotyphlans and other mammals such that eulipotyphlans have more neurons concentrated in an olfactory bulb of similar size than afrotherians, glires and primates. Most strikingly, while the cerebral cortex gains neurons at a faster pace than the olfactory bulb in glires, and afrotherians follow this trend, it is the olfactory bulb that gains neurons at a faster pace than the cerebral cortex in eulipotyphlans, which contradicts the common view that the cerebral cortex is the fastest expanding structure in brain evolution. Our findings emphasize the importance of not using brain structure size as a proxy for numbers of neurons across mammalian orders, and are consistent with the notion that different selective pressures have acted upon the olfactory system of eulipotyphlans, glires and primates, with eulipotyphlans relying more on olfaction for their behavior than glires and primates. Surprisingly, however, the neuronal scaling rules for primates predict that the human olfactory bulb has as many neurons as the larger eulipotyphlan olfactory bulbs, which questions the classification of humans as microsmatic.

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.

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.