Chet C. Sherwood

Prolonged myelination in human neocortical evolution

Nerve myelination facilitates saltatory action potential conduction and exhibits spatiotemporal variation during development associated with the acquisition of behavioral and cognitive maturity. Although human cognitive development is unique, it is not known whether the ontogenetic progression of myelination in the human neocortex is evolutionarily exceptional. In this study, we quantified myelinated axon fiber length density and the expression of myelin-related proteins throughout postnatal life in the somatosensory (areas 3b/3a/1/2), motor (area 4), frontopolar (prefrontal area 10), and visual (areas 17/18) neocortex of chimpanzees (N = 20) and humans (N = 33). Our examination revealed that neocortical myelination is developmentally protracted in humans compared with chimpanzees. In chimpanzees, the density of myelinated axons increased steadily until adult-like levels were achieved at approximately the time of sexual maturity. In contrast, humans displayed slower myelination during childhood, characterized by a delayed period of maturation that extended beyond late adolescence. This comparative research contributes evidence crucial to understanding the evolution of human cognition and behavior, which arises from the unfolding of nervous system development within the context of an enriched cultural environment. Perturbations of normal developmental processes and the decreased expression of myelin-related molecules have been related to psychiatric disorders such as schizophrenia. Thus, these species differences suggest that the human-specific shift in the timing of cortical maturation during adolescence may have implications for vulnerability to certain psychiatric disorders.

Evolution of increased glia–neuron ratios in the human frontal cortex

Evidence from comparative studies of gene expression and evolution suggest that human neocortical neurons may be characterized by unusually high levels of energy metabolism. The current study examined whether there is a disproportionate increase in glial cell density in the human frontal cortex in comparison with other anthropoid primate species (New World monkeys, Old World monkeys, and hominoids) to support greater metabolic demands. Among 18 species of anthropoids, humans displayed the greatest departure from allometric scaling expectations for the density of glia relative to neurons in layer II/III of dorsolateral prefrontal cortex (area 9L). However, the human glia–neuron ratio in this prefrontal region did not differ significantly from allometric predictions based on brain size. Further analyses of glia–neuron ratios across frontal areas 4, 9L, 32, and 44 in a sample of humans, chimpanzees, and macaque monkeys showed that regions involved in specialized human cognitive functions, such as “theory of mind” (area 32) and language (area 44) have not evolved differentially higher requirements for metabolic support. Taken together, these findings suggest that greater metabolic consumption of human neocortical neurons relates to the energetic costs of maintaining expansive dendritic arbors and long-range projecting axons in the context of an enlarged brain.

A natural history of the human mind: tracing evolutionary changes in brain and cognition

Since the last common ancestor shared by modern humans, chimpanzees and bonobos, the lineage leading to Homo sapiens has undergone a substantial change in brain size and organization. As a result, modern humans display striking differences from the living apes in the realm of cognition and linguistic expression. In this article, we review the evolutionary changes that occurred in the descent of Homo sapiens by reconstructing the neural and cognitive traits that would have characterized the last common ancestor and comparing these with the modern human condition. The last common ancestor can be reconstructed to have had a brain of approximately 300–400 g that displayed several unique phylogenetic specializations of development, anatomical organization, and biochemical function. These neuroanatomical substrates contributed to the enhancement of behavioral flexibility and social cognition. With this evolutionary history as precursor, the modern human mind may be conceived as a mosaic of traits inherited from a common ancestry with our close relatives, along with the addition of evolutionary specializations within particular domains. These modern human‐specific cognitive and linguistic adaptations appear to be correlated with enlargement of the neocortex and related structures. Accompanying this general neocortical expansion, certain higher‐order unimodal and multimodal cortical areas have grown disproportionately relative to primary cortical areas. Anatomical and molecular changes have also been identified that might relate to the greater metabolic demand and enhanced synaptic plasticity of modern human brains. Finally, the unique brain growth trajectory of modern humans has made a significant contribution to our species’ cognitive and linguistic abilities.

Metabolic costs and evolutionary implications of human brain development

Significance The metabolic costs of brain development are thought to explain the evolution of humans’ exceptionally slow and protracted childhood growth; however, the costs of the human brain during development are unknown. We used existing PET and MRI data to calculate brain glucose use from birth to adulthood. We find that the brain’s metabolic requirements peak in childhood, when it uses glucose at a rate equivalent to 66% of the body’s resting metabolism and 43% of the body’s daily energy requirement, and that brain glucose demand relates inversely to body growth from infancy to puberty. Our findings support the hypothesis that the unusually high costs of human brain development require a compensatory slowing of childhood body growth. The high energetic costs of human brain development have been hypothesized to explain distinctive human traits, including exceptionally slow and protracted preadult growth. Although widely assumed to constrain life-history evolution, the metabolic requirements of the growing human brain are unknown. We combined previously collected PET and MRI data to calculate the human brain’s glucose use from birth to adulthood, which we compare with body growth rate. We evaluate the strength of brain–body metabolic trade-offs using the ratios of brain glucose uptake to the body’s resting metabolic rate (RMR) and daily energy requirements (DER) expressed in glucose-gram equivalents (glucosermr% and glucoseder%). We find that glucosermr% and glucoseder% do not peak at birth (52.5% and 59.8% of RMR, or 35.4% and 38.7% of DER, for males and females, respectively), when relative brain size is largest, but rather in childhood (66.3% and 65.0% of RMR and 43.3% and 43.8% of DER). Body-weight growth (dw/dt) and both glucosermr% and glucoseder% are strongly, inversely related: soon after birth, increases in brain glucose demand are accompanied by proportionate decreases in dw/dt. Ages of peak brain glucose demand and lowest dw/dt co-occur and subsequent developmental declines in brain metabolism are matched by proportionate increases in dw/dt until puberty. The finding that human brain glucose demands peak during childhood, and evidence that brain metabolism and body growth rate covary inversely across development, support the hypothesis that the high costs of human brain development require compensatory slowing of body growth rate.

Von Economo Neurons in the Elephant Brain

Von Economo neurons (VENs), previously found in humans, all of the great ape species, and four cetacean species, are also present in African and Indian elephants. The VENs in the elephant are primarily found in similar locations to those in the other species. They are most abundant in the frontoinsular cortex (area FI) and are also present at lower density in the anterior cingulate cortex. Additionally, they are found in a dorsolateral prefrontal area and less abundantly in the region of the frontal pole. The VEN morphology appears to have arisen independently in hominids, cetaceans, and elephants, and may reflect a specialization for the rapid transmission of crucial social information in very large brains. Anat Rec 2009.

Total number and volume of Von Economo neurons in the cerebral cortex of cetaceans

Von Economo neurons (VENs) are a type of large, layer V spindle‐shaped neurons that were previously described in humans, great apes, elephants, and some large‐brained cetaceans. Here we report the presence of Von Economo neurons in the anterior cingulate (ACC), anterior insular (AI), and frontopolar (FP) cortices of small odontocetes, including the bottlenose dolphin (Tursiops truncatus), the Rissos dolphin (Grampus griseus), and the beluga whale (Delphinapterus leucas). The total number and volume of VENs and the volume of neighboring layer V pyramidal neurons and layer VI fusiform neurons were obtained by using a design‐based stereologic approach. Two humpback whale (Megaptera novaeangliae) brains were investigated for comparative purposes as representatives of the suborder Mysticeti. Our results show that the distribution of VENs in these cetacean species is comparable to that reported in humans, great apes, and elephants. The number of VENs in these cetaceans is also comparable to data available from great apes, and stereologic estimates indicate that VEN volume follows in these cetacean species a pattern similar to that in hominids, the VENs being larger than neighboring layer V pyramidal cells and conspicuously larger than fusiform neurons of layer VI. The fact that VENs are found in species representative of both cetacean suborders in addition to hominids and elephants suggests that these particular neurons have appeared convergently in phylogenetically unrelated groups of mammals possibly under the influence of comparable selective pressures that influenced specifically the evolution of cortical domains involved in complex cognitive and social/emotional processes. J. Comp. Neurol. 515:243–259, 2009.

Cortical dopaminergic innervation among humans, chimpanzees, and macaque monkeys: A comparative study

In this study, we assessed the possibility that humans differ from other primate species in the supply of dopamine to the frontal cortex. To this end, quantitative comparative analyses were performed among humans, chimpanzees, and macaques using immunohistochemical methods to visualize tyrosine hydroxylase-immunoreactive axons within the cerebral cortex. Axon densities and neuron densities were quantified using computer-assisted stereology. Prefrontal areas 9 and 32 were chosen for evaluation due to their roles in higher-order executive functions and theory of mind, respectively. Primary motor cortex (area 4) was also evaluated because it is not directly associated with cognition. We did not find an overt quantitative increase in cortical dopaminergic innervation in humans relative to the other primates examined. However, several differences in cortical dopaminergic innervation were observed among species which may have functional implications. Specifically, humans exhibited a sublaminar pattern of innervation in layer I of areas 9 and 32 that differed from that of macaques and chimpanzees. Analysis of axon length density to neuron density among species revealed that humans and chimpanzees together deviated from macaques in having increased dopaminergic afferents in layers III and V/VI of areas 9 and 32, but there were no phylogenetic differences in area 4. Finally, morphological specializations of axon coils that may be indicative of cortical plasticity events were observed in humans and chimpanzees, but not macaques. Our findings suggest significant modifications of dopamines role in cortical organization occurred in the evolution of the apes, with further changes in the descent of humans.

Comparative analysis of encephalization in mammals reveals relaxed constraints on anthropoid primate and cetacean brain scaling

There is a well‐established allometric relationship between brain and body mass in mammals. Deviation of relatively increased brain size from this pattern appears to coincide with enhanced cognitive abilities. To examine whether there is a phylogenetic structure to such episodes of changes in encephalization across mammals, we used phylogenetic techniques to analyse brain mass, body mass and encephalization quotient (EQ) among 630 extant mammalian species. Among all mammals, anthropoid primates and odontocete cetaceans have significantly greater variance in EQ, suggesting that evolutionary constraints that result in a strict correlation between brain and body mass have independently become relaxed. Moreover, ancestral state reconstructions of absolute brain mass, body mass and EQ revealed patterns of increase and decrease in EQ within anthropoid primates and cetaceans. We propose both neutral drift and selective factors may have played a role in the evolution of brain–body allometry.

Cortical Orofacial Motor Representation in Old World Monkeys, Great Apes, and Humans

Social life in anthropoid primates is mediated by interindividual communication, involving movements of the orofacial muscles for the production of vocalization and gestural expression. Although phylogenetic diversity has been reported in the auditory and visual communication systems of primates, little is known about the comparative neuroanatomy that subserves orofacial movement. The current study reports results from quantitative image analysis of the region corresponding to orofacial representation of primary motor cortex (Brodmann’s area 4) in several catarrhine primate species (Macaca fascicularis, Papio anubis, Pongo pygmaeus, Gorilla gorilla, Pan troglodytes, and Homo sapiens) using the Grey Level Index method. This cortical region has been implicated in the execution of skilled motor activities such as voluntary facial expression and human speech. Density profiles of the laminar distribution of Nissl-stained neuronal somata were acquired from high-resolution images to quantify cytoarchitectural patterns. Despite general similarity in these profiles across catarrhines, multivariate analysis showed that cytoarchitectural patterns of individuals were more similar within-species versus between-species. Compared to Old World monkeys, the orofacial representation of area 4 in great apes and humans was characterized by an increased relative thickness of layer III and overall lower cell volume densities, providing more neuropil space for interconnections. These phylogenetic differences in microstructure might provide an anatomical substrate for the evolution of greater volitional fine motor control of facial expressions in great apes and humans.

Wernicke's area homologue in chimpanzees (Pan troglodytes) and its relation to the appearance of modern human language

Human language is distinctive compared with the communication systems of other species. Yet, several questions concerning its emergence and evolution remain unresolved. As a means of evaluating the neuroanatomical changes relevant to language that accompanied divergence from the last common ancestor of chimpanzees, bonobos and humans, we defined the cytoarchitectonic boundaries of area Tpt, a component of Wernickes area, in 12 common chimpanzee brains and used design-based stereologic methods to estimate regional volumes, total neuron number and neuron density. In addition, we created a probabilistic map of the location of area Tpt in a template chimpanzee brain coordinate space. Our results show that chimpanzees display significant population-level leftward asymmetry of area Tpt in terms of neuron number, with volume asymmetry approaching significance. Furthermore, asymmetry in the number of neurons in area Tpt was positively correlated with asymmetry of neuron numbers in Brodmanns area 45, a component of Brocas frontal language region. Our findings support the conclusion that leftward asymmetry of Wernickes area originated prior to the appearance of modern human language and before our divergence from the last common ancestor. Moreover, this study provides the first evidence of covariance between asymmetry of anterior and posterior cortical regions that in humans are important to language and other higher order cognitive functions.