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Here, we summarize the current knowledge on cell diversity in the cortex and other brain regions from in vivo mouse models and in vitro models based on pluripotent stem cells. We discuss the mechanisms underlying cell proliferation and temporal progression that leads to the sequential generation of neurons dedicated to different layers of the cortex. We highlight models of corticogenesis from stem cells that recapitulate specific transcriptional and connectivity patterns from different cortical areas. We overview state-of-the art of human brain organoids modeling different brain regions, and we discuss insights into human cortical evolution from stem cells. Finally, we interrogate human brain organoid models for their competence to recapitulate the essence of human brain development.

Because the human brain is considerably larger than those of other primates, it is not surprising that its energy requirements would far exceed that of any of the species within the order. Recently, the development of stem cell technologies and single-cell transcriptomics provides novel ways to address the question of what specific genomic changes underlie the human brain's unique phenotype. In this review, we consider what is currently known about human brain metabolism using a variety of methods from brain imaging and stereology to transcriptomics. Next, we examine novel opportunities that stem cell technologies and single-cell transcriptomics provide to further our knowledge of human brain energetics. These new experimental approaches provide the ability to elucidate the functional effects of changes in genetic sequence and expression levels that potentially had a profound impact on the evolution of the human brain.

BACKGROUND For the followers of criminal anthropology, during the second half of the 19th and the beginning of the 20th century, the association "anatomical anomaly - psyche anomaly" represented an immediate diagnostic tool to identify mental illness and consequently the tendency to become a criminal. In this article, we analyse a clinical report published in 1900 in which the author, Dr. Saporito, described five brains of alienated criminals from the Aversa asylum. METHODS Through the observations of Dr. Saporito's autoptic evaluations and the literature of the times, the beliefs of the positivist science of that time are highlighted. RESULTS The identification of multiple physical anomalies focused on the brains, with particular attention to the alteration at the level of some fissures, could lead to identify psychiatric disorders and criminal tendency. CONCLUSIONS From the observations presented here, the author reiterated that several anomalies recorded in these five brains reproduced atavistic characteristics, which disappeared in the ontogenetic and phylogenetic evolution of the human brain.

The expansion of the cerebral cortex is one of the most distinctive changes in the evolution of the human brain. Cortical expansion and related increases in cortical folding may have contributed to emergence of our capacities for high-order cognitive abilities. Molecular analysis of humans, archaic hominins, and non-human primates has allowed identification of chromosomal regions showing evolutionary changes at different points of our phylogenetic history. In this study, we assessed the contributions of genomic annotations spanning 30 million years to human sulcal morphology measured via MRI in more than 18,000 participants from the UK Biobank. We found that variation within brain-expressed human gained enhancers, regulatory genetic elements that emerged since our last common ancestor with Old World monkeys, explained more trait heritability than expected for the left and right calloso-marginal posterior fissures and the right central sulcus. Intriguingly, these are sulci that have been previously linked to the evolution of locomotion in primates and later on bipedalism in our hominin ancestors.

Humans are unique in their diet, physiology and socio‑reproductive behavior compared to other primates. They are also unique in the ubiquitous adaptation to all biomes and habitats. From an evolutionary perspective, these trends seem to have started about two million years ago, coinciding with the emergence of encephalization, the reduction of the dental apparatus, the adoption of a fully terrestrial lifestyle, resulting in the emergence of the modern anatomical bauplan, the focalization of certain activities in the landscape, the use of stone tools, and the exit from Africa. It is in this period that clear taphonomic evidence of a switch in diet with respect to Pliocene hominins occurred, with the adoption of carnivory. Until now, the degree of carnivorism in early humans remained controversial. A persistent hypothesis is that hominins acquired meat irregularly (potentially as fallback food) and opportunistically through klepto‑foraging. Here, we test this hypothesis and show, in contrast, that the butchery practices of early Pleistocene hominins (unveiled through systematic study of the patterning and intensity of cut marks on their prey) could not have resulted from having frequent secondary access to carcasses. We provide evidence of hominin primary access to animal resources and emphasize the role that meat played in their diets, their ecology and their anatomical evolution, ultimately resulting in the ecologically unrestricted terrestrial adaptation of our species. This has major implications to the evolution of human physiology and potentially for the evolution of the human brain., We thank the Spanish Ministry of Science, Innovation and Universities for funding this research (HAR2017-82463-C4-1-P) and for fellowships to JA,GCA and MVR, and the Ministry of Culture for their funding through the program of Archaeology Abroad. We also thank the Swedish Research Council (Vetenskapsrådet) (AR-HS 2018-01045-3), and the Santander Bank (AR-HS 2018-01045-3) for their funding support. Our thanks also to the Palarq Foundation and E2in2 for financial support.

Recent advances in stem cell, genome editing, and iPSC technologies have made it possible to study human brain evolution using this iPSC-derived brain organoids as a model system. In this chapter, we will explore the evolution of the human brain and the central nervous system and discuss what we can learn from genomic comparisons studies. We will also examine the model organisms used to study gene expression and cell biology and delve into the new world of iPSC-derived brain organoids and what this new model system can tell us about human brain evolution.

A new method provides evidence that evolution of gene activity in the human brain was driven by natural selection., A longstanding hypothesis is that divergence between humans and chimpanzees might have been driven more by regulatory level adaptations than by protein sequence adaptations. This has especially been suggested for regulatory adaptations in the evolution of the human brain. We present a new method to detect positive selection on transcription factor binding sites on the basis of measuring predicted affinity change with a machine learning model of binding. Unlike other methods, this approach requires neither defining a priori neutral sites nor detecting accelerated evolution, thus removing major sources of bias. We scanned the signals of positive selection for CTCF binding sites in 29 human and 11 mouse tissues or cell types. We found that human brain–related cell types have the highest proportion of positive selection. This result is consistent with the view that adaptive evolution to gene regulation has played an important role in evolution of the human brain.

A human-specific gene is a determinant of the cognitive architecture of the human cerebral cortex

Background The remarkable abilities of the human brain are distinctive features that set us apart from other animals. However, our understanding of how the brain has changed in the human lineage remains incomplete, but is essential for understanding cognition, behavior, and brain disorders in humans. Here, we compared the expression trajectory in brain development between humans and rhesus macaques (Macaca mulatta) to explore their divergent transcriptome profiles. Results Results showed that brain development could be divided into two stages, with a demarcation date in a range between 25 and 26 postconception weeks (PCW) for humans and 17-23PCWfor rhesus macaques, rather than birth time that have been widely used as a uniform demarcation time of neurodevelopment across species. Dynamic network biomarker (DNB) analysis revealed that the two demarcation dates were transition phases during brain development, after which the brain transcriptome profiles underwent critical transitions characterized by highly fluctuating DNB molecules. We also found that changes between early and later brain developmental stages (as defined by the demarcation points) were substantially greater in the human brain than in the macaque brain. To explore the molecular mechanism underlying prolonged timing during early human brain development, we carried out expression heterochrony tests. Results demonstrated that compared to macaques, more heterochronic genes exhibited neoteny during early human brain development, consistent with the delayed demarcation time in the human lineage, and proving that neoteny in human brain development could be traced to the prenatal period. We further constructed transcriptional networks to explore the profile of early human brain development and identified the hub gene RBFOX1 as playing an important role in regulating early brain development. We also found RBFOX1 evolved rapidly in its non-coding regions, indicating that this gene played an important role in human brain evolution. Our findings provide evidence that RBFOX1 is a likely key hub gene in early human brain development and evolution. Conclusions By comparing gene expression profiles between humans and macaques, we found divergent expression trajectories between the two species, which deepens our understanding of the evolution of the human brain.

A long standing hypothesis is that divergence between humans and chimpanzees might have been driven more by regulatory level adaptions than by protein sequence adaptations. This has especially been suggested for regulatory adaptions in the evolution of the human brain. There is some support for this hypothesis, but it has been limited by the lack of a reliable and powerful way to detect positive selection on regulatory sequences. We present a new method to detect positive selection on transcription factor binding sites, based on Orr’s sign test applied to a machine learning model of binding. Unlike other methods, this requires neither defining a priori neutral sites, nor detecting accelerated evolution, thus removing major sources of bias. The method is validated in flies, mice, and primates, by a McDonald-Kreitman-like measure of polymorphism vs. divergence, by experimental binding site gains and losses, and by changes in expression levels. We scanned the signals of positive selection for CTCF binding sites in 29 human and 11 mouse tissues or cell types. We found that human brain related cell types have the highest proportion of positive selection. This is consistent with the importance of adaptive evolution on gene regulation in the evolution of the human brain.

Humans are highly social animals whose survival and well-being depend on their capacity to cooperate in complex social settings. Advances in anthropology and psychology have demonstrated the importance of cooperation for enhancing social cohesion and minimizing conflict. The understanding of social behavior is informed by the notion of social cognition, a set of mental operations including emotion perception, mentalizing, and empathy. The social brain hypothesis posits that the mammalian brain has enlarged over evolution to meet the challenges of social life, culminating in a large human brain well adapted for social cognition. The structures subserving social cognition are mainly located in the frontal and temporal lobes, and although gray matter is critical, social cognition also requires white matter. Whereas the social brain hypothesis assumes that brain enlargement has been driven by neocortical expansion, cerebral white matter has expanded even more robustly than the neocortex, coinciding with the emergence of social cognition. White matter expansion is most evident in the frontal and temporal lobes, where it enhances connectivity between regions critical for social cognition. Myelination has, in turn, conferred adaptive social advantages by enabling prompt empathic concern for offspring and by strengthening networks that support cooperation and the related capacities of altruism and morality. Social cognition deficits related to myelinated tract involvement occur in many disorders, including stroke, Binswanger disease, traumatic brain injury, multiple sclerosis, glioma, and behavioral variant frontotemporal dementia. The contribution of white matter to social cognition can be conceptualized as the enhancement of cooperation through brain connectivity.

Evolutionary perspective is critical for understanding human biology, human medicine, and the traits that make human beings unique. One of the crucial characteristics that sets humans apart from other extant species is our cognitive ability, which allows for complex processes including symbolic thought, theory of mind, and syntactical-grammatical language, and is thought to arise from the expansion and specialization of the human nervous system. It has been hypothesized that the same evolutionary changes that allowed us to develop these valuable skills made humans susceptible to neurodevelopmental and neurodegenerative disease. Unfortunately, our lack of access to our extinct ancestors makes this a difficult hypothesis to test, but recent collaborations between the fields of evolution, genetics, genomics, neuroscience, neurology and psychiatry have begun to provide some clues. Here, we will outline recent work in those fields that have utilized our growing knowledge of disease risk genes and loci, identified by wide-scale genetic studies, and nervous system development and function to draw conclusions about the impact of human-specific aspects of evolution. We will discuss studies that assess evolution at a variety of scales including at the levels of whole brain regions, cell types, synapses, metabolic processes, gene expression patterns, and gene regulation. At all of these levels, there is preliminary evidence that human-specific brain features are linked to neurodevelopmental and neurodegenerative disease risk.

Adrenarche, the post-natal rise of DHEA and DHEAS, is unique to humans and the African Apes. Recent findings have linked DHEA in humans to the development of the left dorsolateral prefrontal cortex (LDPFC) between the ages of 4-8 years and the right temporoparietal junction (rTPJ) from 7 to 12 years of age. Given the association of the LDLPFC with the 5-to-8 transition and the rTPJ with mentalizing during middle childhood DHEA may have played an important role in the evolution of the human brain. I argue that increasing protein in the diet over the course of human evolution not only increased levels of DHEAS, but linked meat consumption with brain development during the important 5- to-8 transition. Consumption of animal protein has been associated with IGF-1, implicated in the development of the adrenal zona reticularis (ZR), the site of DHEAS production. In humans and chimps, the zona reticularis emerges at 3-4 years, along with the onset of DHEA/S production. For chimps this coincides with weaning and peak synaptogenesis. Among humans, weaning is completed around 2 ½ years, while synaptogenesis peaks around 5 years. Thus, in chimpanzees, early cortical maturation is tied to the mother; in humans it may be associated with post-weaning provisioning by others. I call for further research on adrenarche among the African apes as a critical comparison to humans. I also suggest research in subsistence populations to establish the role of nutrition and energetics in the timing of adrenarche and the onset of middle childhood.

The evolutionary origin of Primates' exceptionally large brains is still highly debated. Two competing explanations have received much support: the ecological hypothesis and the social brain hypothesis (SBH). We tested the SBH in (n = 82) baboons (Papio anubis) belonging to the same research centre but housed in groups with size ranging from 2 to 63 individuals. We found that baboons living in larger social groups had larger brains. This effect was driven mainly by white matter volume and to a lesser extent by grey matter volume but not by the cerebrospinal fluid. In comparison, the size of the enclosure, an ecological variable, had no such effect. In contrast to the current re-emphasis on potential ecological drivers of primate brain evolution, the present study provides renewed support for the social brain hypothesis and suggests that the social brain plastically responds to group size. Many factors may well influence brain size, yet accumulating evidence suggests that the complexity of social life might be an important determinant of brain size in primates.

According to Dunbar’s social brain hypothesis, brain capacity puts a limit on the size of social network in humans. At the same time, emotional-cognitive systems such as attachment and different relational models ( Fiske, 1991 ) may also act as driving forces behind network structure underlying relationship quality of the various ego-centered layers. The aim of our study was to examine how these cognitive systems may contribute to network organization. We examined the two inner layers of the ego-network in 274 volunteers, the support and sympathy groups, as well as close family members in comparison to friends within the support group, in terms of attachment security and underlying relational models.

This Editorial elaborates on innovative concepts presented at the 2nd European Conference of Biomedical Research and Treatments for autism held in Bari, Italy, in November 2017. We discuss the recent publication of a paper describing how relativistic time dilation at the DNA level can lead to novel approaches in disease prevention and cure, and we elaborate on the role of the human microbiota in restoring quantum entanglement at the DNA level. According to this hypothesis, microbial degradation of a glycosaminoglycan, chondroitin sulfate, leads to restauration of gene expression, induces general and sequence-specific relativistic time dilation, restores DNA quantum entanglement, and improves the ability of DNA to retain, process and transmit information both at the biochemical and the quantum levels. It can be argued that these processes played a role in the evolution of the human brain and consciousness. Fermented aliments that today would be defined as “probiotics” were the first processed foods eaten by early humans, and it is conceivable that the effects of the microbes in those aliments on the chondroitin sulfate, coming from cartilage of animals hunted or scavenged, may have led to the biochemical, relativistic and quantum effects responsible for human evolution. Finally, we discuss the implications in the field of autism where the theory of consciousness based on quantum biology presents exciting and innovative perspectives for prevention and cure.

Evolution often deals in genomic trade-offs: changes in the genome that are beneficial overall persist even though they also produce disease in a subset of individuals. Here, we explore the possibility that such trade-offs have occurred as part of the evolution of the human brain. Specifically, we provide support for the possibility that the same key genes that have been major contributors to the rapid evolutionary expansion of the human brain and its exceptional cognitive capacity also, in different combinations, are significant contributors to autism and schizophrenia. Furthermore, the model proposes that one of the primary genes behind this trade-off may not technically be “a gene” or “genes” but rather are the highly duplicated sequences that encode the Olduvai protein domain family (formerly called DUF1220). This is not an entirely new idea. Others have proposed that the same genes involved in schizophrenia were also critical to the rapid expansion of the human brain, a view that has been expressed as “the same ‘genes’ that drive us mad have made us human”. What is new is that a “gene”, or more precisely a protein domain family, has been found that may satisfy these requirements.

Living in large groups and maintaining extensive social relationships, as humans do, requires special social capabilities. Past research has shown that social cognitive abilities predict people’s social network size. To extend these findings we explored the role of a social emotional ability, and investigated how empathic abilities shape people’s social network. In line with the social brain hypothesis the findings show that dispositional empathic abilities (IRI), and empathic concern specifically, predict how many close relationships people maintain. The study also found that emphatic abilities are strategically used in people’s social network, with more empathy exercised in the support group with closer relationships. The findings further demonstrate the social function of empathy and highlight the importance of understanding empathy in terms of its strategic exercise among various social relationships.

Animals living in social groups will almost inevitably experience competition for limited resources. One consequence of competition can be agonism, an activity that is not only costly to participate in at the individual level but potentially also at the group level due the detrimental effects that agonism can have on group stability and cohesion. Agonism rates across primate species have previously been associated with group size and terrestriality; therefore primates, particularly those in large groups, should develop strategies to mitigate or counter-act agonism. Here, we use phylogenetically controlled analyses to evaluate whether the known relationship between brain size and group size may partially reflect an association between agonism and brain size in large groups. We find strong positive associations between group level agonism and 2 measures of brain size (endocranial volume and neocortex ratio) in 45 separate populations across 23 different primate species. In contrast, dyadic (pair-wise) rates of agonism are inversely associated with group size and not with brain size. Moreover, we find a distinct absence of relationships between agonism and the prevalence of prosocial, cooperative behaviors. That overall rates of agonism increase but dyadic rates decrease with group size suggests that individuals in larger groups either can buffer aggression better or only species with low levels of dyadic conflict can maintain large groups.

Brain structures within an individual can change during development through modification of individual neuron morphology together with alteration of neuron numbers. Differences in the same or analogous brain structures from different species can reflect behavioral pattern variation among these species fixed by natural selection. This study used insects from two different taxonomic groups to address such brain structure changes at these two time scales: developmental and evolutionary. Mushroom bodies, as an integrative sensory center involved in learning and memory in insects, were the main structure surveyed to illustrate changes in higher brain centers in both projects. In the developmental study, the changes of higher brain centers in red flour beetle, Tribolium castaneaum, were described from late larva through adulthood. The mechanisms detected for change of brain included axon reorganization, compartment enlargement and adult neurogenesis. In a second study to comparing brain structure differences across species, with an effort to address an evolutionary question, a significant difference in mushroom body volumes from different species of eusocial termites was found. This suggests that it is possible to independently test the social brain hypothesis, which was developed for very different animal lineages including primates, within this group of successful social insects.

The social brain hypothesis is regarded as a powerful theory to understand social cognition. Individuals with autism spectrum disorder (ASD) have specific deficits in social and communicative behavior, but the exact relationship between these deficits and abnormalities in the social brain remains unclear. The high heritability of this disorder makes it important to focus on the first-degree relatives of those affected. Research focusing on genetically at-risk (yet healthy) relatives of patients with ASD is critical to the study of neuroimaging endophenotypes. We conducted a voxel-wise activation likelihood estimation (ALE) meta-analysis of 9 functional neuroimaging studies published during the period from 2006 to 2018. These studies included 200 individuals with ASD, 216 unaffected family members (UF), and 235 typical development controls (TD). The voxel-wise significance threshold was p0.01 (uncorrected p = 0.001).The ALE meta-analyses showed hyperactivation in the inferior frontal gyrus (IFG) and superior temporal gyrus (STG) among individuals with ASD and UF, compared with TD individuals. Group comparisons showed greater likelihood of hyperactivation in the amygdala for ASD, compared with UF and TD.

While the human brain is clearly large relative to body size, less is known about the timing of brain and brain component expansion within primates and the relative magnitude of volumetric increases. Using Bayesian phylogenetic comparative methods and data for both extant and fossil species, we identified that a distinct shift in brain-body scaling occurred as hominins diverged from other primates, and again as humans and Neanderthals diverged from other hominins. Within hominins, we detected a pattern of directional and accelerating evolution towards larger brains, consistent with a positive feedback process in the evolution of the human brain. Contrary to widespread assumptions, we found that the human neocortex is not exceptionally large relative to other brain structures. Instead, our analyses revealed a single increase in relative neocortex volume at the origin of haplorrhines, and an increase in relative cerebellar volume in apes., eLife digest Humans have much larger brains than other primates, but it is not clear exactly when and how this difference emerged during evolution. Some scientists believe that the expansion of a part of the brain called the neocortex – which handles sight, hearing, conscious decision-making and language – drove the increase in the size of the human brain. Newer studies have challenged that idea. One way to learn more about how humans evolved bigger brains is to compare the size of the brain, and specific parts of the brain, between humans and our closest relatives: non-human primates. To make accurate comparisons, scientists must account for many factors. Closely related primates may have more similar traits because they more recently shared a common ancestor. This means the evolutionary relationships between species need to be considered. Larger animals also tend to have larger brains so it is important to consider body size, too. Now, Miller at al. show that the human brain is much larger than expected even after accounting for these factors, and that increases in brain size accelerated over the course of early human evolution. In the analyses, the brain and skull sizes of different living primate species, like chimpanzees and gorillas, and fossils of extinct primates, including Neanderthals, were compared using mathematical models. These findings suggest that larger brains provided fitness advantages that led to large brain sizes in modern humans and Neanderthals. These increases in brain size were not driven by disproportionate growth in the neocortex alone, but rather by increases in the size of many parts of the brain. Increases in the relative size of the cerebellum, which is essential for balance and movement, were also important.

During the course of evolution the human brain has increased in size and complexity, ultimately these differences are the result of changes at the genetic level. Identifying and characterizing molecular evolution requires an understanding of both the genetic underpinning of the system as well as the comparative genetic tools to identify signatures of selection. This chapter aims to describe our current understanding of the genetics of human brain evolution. Primarily this is the story of the evolution of the human brain since our last common ape ancestor, but where relevant we will also discuss changes that are unique to the primate brain (compared to other mammals) or various other lineages in the evolution of humans more generally. It will focus on genetic changes that both directly affected the development and function of the brain as well as those that have indirectly influenced brain evolution through both prenatal and postnatal environment. This review is not meant to be exhaustive, but rather to begin to construct a general framework for understanding the full array of data being generated.

Huntington disease is a neurodegenerative disorder caused by a gene (HTT) with a unique feature of trinucleotide repeats ranging from 10 to 35 in healthy people; when expanded beyond 39 repeats, Huntington disease develops. Animal models demonstrate that HTT is vital to brain development; however, this has not been studied in humans. Moreover, evidence suggests that triplet repeat genes may have been vital in evolution of the human brain. Here we evaluate brain structure using magnetic resonance imaging and brain function using cognitive tests in a sample of school-aged children ages 6 to 18 years old. DNA samples were processed to quantify the number of CAG repeats within HTT. We find that the number of repeats in HTT, below disease threshold, confers advantageous changes in brain structure and general intelligence (IQ): the higher the number of repeats, the greater the change in brain structure, and the higher the IQ. The pattern of structural brain changes associated with HTT is strikingly different between males and females. HTT may confer an advantage or a disadvantage depending on the repeat length, playing a key role in either the evolution of a superior human brain or development of a uniquely human brain disease. © 2016 Wiley Periodicals, Inc.

The social brain hypothesis fixes to 150 the number of social relationships we are able to maintain. Similar cognitive constraints emerge in several aspects of our daily life, from our mobility up to the way we communicate, and might even affect the way we consume information online. Indeed, despite the unprecedented amount of information we can access online, our attention span still remains limited. Furthermore, recent studies showed the tendency of users to ignore dissenting information but to interact with information adhering to their point of view. In this paper, we quantitatively analyze users' attention economy in news consumption on social media by analyzing 14M users interacting with 583 news outlets (pages) on Facebook over a time span of 6 years. In particular, we explore how users distribute their activity across news pages and topics. We find that, independently of their activity, users show the tendency to follow a very limited number of pages. On the other hand, users tend to interact with almost all the topics presented by their favored pages. Finally, we introduce a taxonomy accounting for users behavior to distinguish between patterns of selective exposure and interest. Our findings suggest that segregation of users in echo chambers might be an emerging effect of users' activity on social media and that selective exposure -- i.e. the tendency of users to consume information interest coherent with their preferences -- could be a major driver in their consumption patterns., Comment: PLOS One Published: March 13, 2020

Rising atmospheric oxygen (O2) levels provided a selective pressure for the evolution of O2-dependent micro-organisms that began with the autotrophic eukaryotes. Since these primordial times, the respiring mammalian cell has become entirely dependent on the constancy of electron flow with molecular O2 serving as the terminal electron acceptor in mitochondrial oxidative phosphorylation. Indeed, the ability to “sense” O2 and maintain homeostasis is considered one of the most important roles of the central nervous system (CNS) and likely represented a major driving force in the evolution of the human brain. Today, modern humans have evolved with an oversized brain committed to a continually active state and as a consequence, paradoxically vulnerable to failure if the O2 supply is interrupted. However, our pre-occupation with O2, the elixir of life, obscures the fact that it is a gas with a Janus Face, capable of sustaining life in physiologically controlled amounts yet paradoxically deadly to the CNS when in excess. A closer look at its quantum structure reveals precisely why; the triplet ground state diatomic O2 molecule is paramagnetic and exists in air as a free radical, constrained from reacting aggressively with the brain’s organic molecules due to its “spin restriction”, a thermodynamic quirk of evolutionary fate. By further exploring O2’s free radical “quantum quirkiness” including emergent quantum physiological phenomena, our understanding of precisely how the human brain senses O2 deprivation (hypoxia) and the elaborate redox-signaling defense mechanisms that defend O2 homeostasis has the potential to offer unique insights into the pathophysiology and treatment of human brain disease.

BackgroundBrain size is expected to evolve by a balance between cognitive benefits and energetic costs. Several influential hypotheses have suggested that large brains may be especially beneficial in social contexts. Group living and competition may pose unique cognitive challenges to individuals and favor the evolution of increased cognitive ability. Evidence comes from comparative studies on the link between social complexity and brain morphology, but the strength of empirical support has recently been challenged. In addition, the behavioral mechanisms that would link cognitive ability to sociality are rarely studied. Here we take an alternative approach and investigate experimentally how brain size can relate to the social competence of individuals within species, a problem that so far has remained unresolved. We use the unique guppy brain size selection line model system to evaluate whether large brains are advantageous by allowing individuals to better assess their performance in a social contest situation. Based on theoretical literature, we predict that contest duration should depend on the brain size of the loser, as it is the capitulation of the losing individual that ends the fight.ResultsFirst, we show that studying the movement of competitors during contests allows for precise estimation of the dominance timeline in guppies, even when overt aggression is typically one-sided and delayed. Second, we staged contests between pairs of male that had been artificially selected for large and small relative brain size, with demonstrated differences in cognitive ability. We show that dominance was established much earlier in contests with large-brained losers, whereas the brain size of the winner had no effect. Following our prediction, large-brained individuals gave up more quickly when they were going to lose.ConclusionsThese results suggest that large-brained individuals assess their performance in contests better and that social competence indeed can depend on brain size. Conflict resolution may therefore be an important behavioral mechanism behind macro-evolutionary patterns between sociality and brain size. Since conflict is ubiquitous among group-living animals, the possible effects of the social environment on the evolution of cognition may be more broadly applicable than previously thought.

We investigated associations between online and offline socialising and groups of social ties as postulated by the Social Brain Hypothesis (SBH). An online survey of social media use, social satisfaction and loneliness generated 249 complete responses from a sample of staff and students at the University of Manchester. Regression-based analyses showed that offline social activities and social time were positively associated with size of a core support group and social satisfaction. In contrast, social media time was positively associated with social satisfaction and the size of the total network, while the number of online contacts was positively related to social satisfaction, size of a wider sympathy group and total network size. No effect for loneliness was found. The number of ties reported for each SBH group was similar to that in previous studies. The more intimate support group (∼5) appears to be more closely connected with offline social activities, whereas social media use and contacts influence the less intimate sympathy group (∼15) and total network (∼150). These findings provide further support for functional differences between different layers of closeness in personal networks, and they help us in further defining the boundaries of relationship enhancement via communication technology.

Human social cognitive abilities share derived attributes with other primates, but humans excel uniquely with regard to skills such as theory of mind, perspective-taking, sharing intentions and using language. Even these apparently unique abilities, however, must be supported by neurochemistry that is in turn developmentally dependent on genes derived from our primate lineage. In the last decade, epigenetic processes have emerged as an influence on differences both within and between mammalian species, and the brain is a major target for epigenetic processes regulating gene expression. This short review looks at how epigenetic processes may have contributed to human social cognitive evolution, how this relates to differences between human and non-human primate social cognition and to what extent this is consistent with the social brain hypothesis, i.e. increasing human sociality as a driver rather than a consequence of human brain evolution. The evidence ranges from general trends in maternally and paternally expressed genes influencing different parts of the brain, quantitative differences in mechanisms such as DNA methylation and gene expression in the brains of humans and other primates and examples of species-specific epigenetic regulation of genes associated with social cognition and language.

It is important that the cortex of the australopithecine brain was apparently organized toward the modern human condition; knowing the precise amount of increase in relative size of temporal or parietal cortex would not add anything essential to understanding of the fact. The chapter describes some concrete evidence for brain reorganization resulting from studies on the early hominid endocasts from South Africa. It also describes an admittedly speculative model of early hominid evolution. There are three ways by which one may approach the evolution of the human brain: the study of the only empirical evidence of brain evolution, paleoneurology, or the study of endocasts; neurological study of an extant comparative series; study of neurological parameters and behavior, which can include neurophysiology, neurochemistry, inbred strains, and neurological genetics. Data on the non-neural contributions to cranial capacity are needed for all hominoids to provide better estimates of neural contents.

The social brain hypothesis posits that dedicated neural systems process social information. In support of this, neurophysiological data have shown that some brain regions are specialized for representing faces. It remains unknown, however, whether distinct anatomical substrates also represent more complex social variables, like the hierarchical rank of individuals within a social group. Here we show that the primate amygdala encodes the hierarchical rank of individuals in the same neuronal ensembles that encode the rewards associated with non-social stimuli. By contrast, orbitofrontal and anterior cingulate cortices lack strong representations of hierarchical rank while still representing reward values. These results challenge the conventional view that dedicated neural systems process social information. Instead, information about hierarchical rank – which contributes to the assessment of the social value of individuals within a group – is linked within the amygdala to representations of rewards associated with non-social stimuli.

The evolutionary expansion of the brain is among the most distinctive morphological features of mammals. During the past decades, considerable progress has been made in explaining brain evolution in terms of physical and adaptive principles. The objective of this chapter is to present current perspectives on primate brain evolution, especially in humans, and to examine some of the design principles and operational modes that underlie the brain's information processing capacity. It is shown that local wiring and cortical folding is a simple design principle that enables brains to be more compact and faster with increasing size. Scaling studies and computational models, furthermore, indicate that the functional capacity of the human brain is inherently constrained by its neural architecture and signal processing capacity and that with our brain we have nearly reached the physical limits and evolutionary potential of a neural-based system.

The brain is ultimately the centerpiece of neuroscience. However, the human brain does not appear fully formed out of nowhere. It is the product of a long process of evolution over many hundreds of millions of years, beginning with the first neural nets evolved by primitive invertebrates. These early neural systems were largely concerned with managing somatic processes—feeding, digestion, movement, orientation. The evolution of the vertebrate nervous system, based around a recognizable brain and a spinal cord encased in bony protecting vertebrae, marked a sea change in both efficiency and scale. The larger body size of vertebrates not only made a larger brain necessary (more somatic tissue to manage) but also provided the energetic and nutritional capacity to support a larger brain.

A wide range of complex social behaviors are facilitated by the recognition of individual conspecifics. Individual recognition requires sufficient phenotypic variation to provide identity information as well as receivers that process and respond to identity information. Understanding how a complex trait such as individual recognition evolves requires that we consider how each component has evolved. Previous comparative studies have examined phenotypic variability in senders and receiver learning abilities, although little work has compared receiver responses to identity information among related species with and without individual recognition. Here, we compare responses to identity information in two Polistes paper wasps: P. fuscatus, which visually recognizes individuals, and P. metricus, which does not normally show evidence of individual recognition. Although the species differ in individual recognition, the results of this study show that receiver responses to experimentally manipulated identity information are surprisingly similar in both species. Receivers direct less aggression toward identifiable individuals than unidentifiable individuals. Therefore, the responses necessary for individual recognition may pre-date its evolution in the P. fuscatus lineage. Additionally, our data demonstrate the apparent binary differences in a complex behavior between the two species, such as individual recognition, likely involve incremental differences along a number of axes.

The evolution of the large and complex brain was a big advantage to early humans in their social interactions and encounters with unfamiliar habitats. But it was not without a high cost to women’s sexual and reproductive health. The developing fetal brain needs and consumes a lot of energy. To meet this need, a more intensely invasive placenta evolved and with it, the risk of excessive bleeding when the placenta separates partially or completely from the uterine wall, a major cause of maternal death. Delivering the large fetal head is an obstetric dilemma, particularly with the relatively narrow and irregular bipedal pelvis. The additional long time needed for the postnatal growth of the brain dictated the necessity for continued paternal investment. To strengthen the pair bond, sex was completely dissociated from reproduction and ovulation was concealed. However women then became vulnerable to sexual violence, sexually transmitted infections, and unwanted pregnancy. Recently, the human brain has been repaying women in the currency of modern science, including making motherhood safer and developing women-controlled contraceptive technologies. Scientific challenges still stand. For example, the modern woman has to cope with the burden of a reproductive system evolved for a hunter gatherer. Women have already fulfilled the divine obligation to replenish the earth, and it is time for science to help women to finally emerge from behind the mother.

A key driver of brain evolution in primates and humans is the cognitive demands arising from managing social relationships. In primates, grooming plays a key role in maintaining these relationships, but the time that can be devoted to grooming is inherently limited. Communication may act as an additional, more time-efficient bonding mechanism to grooming, but how patterns of communication are related to patterns of sociality is still poorly understood. We used social network analysis to examine the associations between close proximity (duration of time spent within 10 m per hour spent in the same party), grooming, vocal communication, and gestural communication (duration of time and frequency of behavior per hour spent within 10 m) in wild chimpanzees. This study examined hypotheses formulated a priori and the results were not corrected for multiple testing. Chimpanzees had differentiated social relationships, with focal chimpanzees maintaining some level of proximity to almost all group members, but directing gestures at and grooming with a smaller number of preferred social partners. Pairs of chimpanzees that had high levels of close proximity had higher rates of grooming. Importantly, higher rates of gestural communication were also positively associated with levels of proximity, and specifically gestures associated with affiliation (greeting, gesture to mutually groom) were related to proximity. Synchronized low-intensity pant-hoots were also positively related to proximity in pairs of chimpanzees. Further, there were differences in the size of individual chimpanzees' proximity networks—the number of social relationships they maintained with others. Focal chimpanzees with larger proximity networks had a higher rate of both synchronized low- intensity pant-hoots and synchronized high-intensity pant-hoots. These results suggest that in addition to grooming, both gestures and synchronized vocalizations may play key roles in allowing chimpanzees to manage a large and differentiated set of social relationships. Gestures may be important in reducing the aggression arising from being in close proximity to others, allowing for proximity to be maintained for longer and facilitating grooming. Vocalizations may allow chimpanzees to communicate with a larger number of recipients than gestures and the synchronized nature of the pant-hoot calls may facilitate social bonding of more numerous social relationships. As group sizes increased through human evolution, both gestures and synchronized vocalizations may have played important roles in bonding social relationships in a more time-efficient manner than grooming.

The social brain hypothesis proposes that large neocortex size evolved to support cognitively demanding social interactions. Accordingly, previous studies have observed that larger orbitofrontal and amygdala structures predict the size of an individual's social network. However, it remains uncertain how an individual's social connectedness reported by other people is associated with the social brain volume. In this study, we found that a greater in-degree network size, a measure of social ties identified by a subject's social connections rather than by the subject, significantly correlated with a larger regional volume of the orbitofrontal cortex, dorsomedial prefrontal cortex and lingual gyrus. By contrast, out-degree size, which is based on an individual's self-perceived connectedness, showed no associations. Meta-analytic reverse inference further revealed that regional volume pattern of in-degree size was specifically involved in social inference ability. These findings were possible because our dataset contained the social networks of an entire village, i.e. a global network. The results suggest that the in-degree aspect of social network size not only confirms the previously reported brain correlates of the social network but also shows an association in brain regions involved in the ability to infer other people's minds. This study provides insight into understanding how the social brain is uniquely associated with sociocentric measures derived from a global network.

Numerous field researchers have described cooperative hunting in social carnivores, but experimental evidence of cooperative problem solving typically derives from laboratory studies of nonhuman primates. We present the first experimental evidence of cooperation in a social carnivore, the spotted hyaena, Crocuta crocuta. Eight captive hyaenas, paired in 13 combinations, coordinated their behaviour temporally and spatially to solve cooperation tasks that modelled group-hunting strategies. Unlike many primates that cooperate infrequently or require extensive shaping, spotted hyaenas displayed a natural aptitude for teamwork: all teams achieved success rapidly, repeatedly, and without specific training. Social influences on cooperative performance included an audience effect that could influence party formation and hunting success in the wild. Performance also varied across dyads, notably with rank-related aggression between partners impairing performance. Efficiency improved as partners increasingly attended to one another and coordinated their actions. Lastly, experienced cooperators modified their behaviour to accommodate a naive companion, using visual monitoring and tracking to promote coordination. We suggest that social carnivores should be considered relevant models for the study of cooperative problem solving, as their abilities provide a comparative framework for testing theories about the mechanisms of social learning and the evolution of intelligence.

Many of the most distinctive attributes of our species are a product of our brains. To understand the function, development, variability, and evolution of the human brain, we must engage with the field of neuroscience. Neuroscientific methods can be used to investigate research topics that are of special interest to anthropologists, such as the neural bases of primate behavioral diversity, human brain evolution, and human brain development. Traditional neuroscience methods had to rely on investigation of postmortem brains, as well as invasive studies in living nonhuman primates. However, recent neuroimaging methods have made it possible to compare living human and nonhuman primate brains using noninvasive techniques such as structural and functional magnetic resonance imaging, positron emission tomography, and diffusion tensor imaging. These methods are providing an integrated picture of brain structure and function that was not previously available. With a combination of these traditional and modern neuroscience methods, we are beginning to explore and understand the neural bases of some of the most distinctive cognitive and behavioral attributes of the human species, including language, tool use, altruism, and mental self-projection, and we can now begin to propose plausible scenarios by which the neural substrates supporting these human specializations evolved from pre-existing neural circuitry serving related functions in common ancestors we shared with the living nonhuman primates. Consideration of the process of neurodevelopment suggests plausible mechanisms by which the highly encephalized human brain might have evolved. Neurodevelopmental studies also demonstrate that experience can shape both brain structure and function, providing a mechanism by which people of different cultures learn to act and think differently. Finally, not only can anthropologists benefit from neuroscience, neuroscience can benefit from the more sophisticated concept of evolution that anthropology offers, including an appreciation of evolutionary diversity as well as consideration of the process by which the human brain was formed during evolution. Yrbk Phys Anthropol 51:2–32, 2008. © 2008 Wiley-Liss, Inc.

Although the study of the human brain is a rapidly developing and expanding science, we must take pause to examine the historical and evolutionary events that helped shape the brain of Homo sapiens. From an examination of the human lineage to a discussion of evolutionary principles, we describe the basic principles and theories behind the evolution of the human brain. Specifically, we examine several theories concerning changes in overall brain size during hominid evolution and relate them to the fossil record. This overview is intended to provide a broad understanding of some of the controversial issues that are currently being debated in the multidisciplinary field of brain evolution research.

Humans usually attribute themselves the prerogative of being the pinnacle of evolution. They have large brains with many billion neurons and glial cells (Lent et al., 2012), trillions of synapses and besides all, a plastic hardware that may change either subtly or strongly in response to the external or internal environment (Tovar-Moll et al., 2014). With this hypercomplex apparatus, they are capable of very sophisticated inward computations and outward behaviors that include self-recognition, metacognition, different forms of language expression and reception, prediction of future events, planning and performing long streams of motor acts, subtle emotional feelings, and many other exceedingly complex properties. The main challenge for research is: how do we explain this gigantic achievement of evolution? Is it a direct consequence of having acquired a brain larger than our primate ancestors, with huge numbers of computational units? Would it be determined by a particular way these units came to relate to each other, building up logic circuits of powerful capacities? What along development has “made the difference” for the construction of such a complex brain machine? How much of this complexity is innate, how much is sculpted by influence of the external world, by social interaction with our human fellows, and by the history of our own mental trajectory along life? This special issue of Frontiers addresses some of these intriguing issues. It is comprised of ten reviews by experts in the field. A reductionist approach is taken by Seth Dobson from Dartmouth College, and Lauren Brent from Duke University, USA. They examine how genomic features of individuals link up to behavioral patterns, in health and disease. Their hypothesis is that polymorphisms of the serotonin transporter gene, typical of primates including humans, offer allelic diversity that make some of us more prone to face adverse social situations (those expressing low levels of the transporter proteins), while others deal better with nonconflictive daily situations (those with high levels). Having two different alleles, therefore, provides long-term benefits to the species to face diverse competition levels within the social group. Branka Hrvoj-Mihic and her collaborators from the University of California at San Diego, USA, comment about an old suggestion by Greenough et al. (1987) on the two basic mechanisms of plasticity: experience-expectant plasticity, by which the brain is provided by development with exuberant hardware (connections, dendrites, synapses), sculpted postnatally to achieve the best configuration for survival; and experience-dependent plasticity, associated to the critical periods in development, by which our late-maturing brain allows change and modulation oriented by environmental input. They argue that the brain faces two opposing needs along life: one is to maintain its circuitry functionally stable, the other is to provide it with enough flexibility (=plasticity) to respond appropriately to the environment. Franco Cauda and his colleagues from the University of Turin, Italy, review the role of an intriguing cortical cell—the von Economo's neuron—described almost 100 years ago (von Economo and Koskinas, 1925). Present in large-brained mammals, including humans, these fusiform neurons are thought to participate in the conscious perception of bodily states, related to the “sentient-self” as proposed by Bud Craig (2010), as well as to differentiation between the self, the others, and the external environment, a strong ability that humans acquired along evolution. More common and universal than von Economo's neurons are the commissural ones. Commissures are inter-hemispheric connections that exist from lampreys to humans. In the latter, the number of commissures has increased to at least six, and the amount of commissural axons connecting the cerebral hemispheres has reached some hundred millions in humans. This evolutionary trajectory as related to developmental mechanisms is reviewed by Rodrigo Suarez and his colleagues from Queensland Brain Institute, Australia. The corpus callosum, in particular, is the target of their interest, and the knowledge of the developmental events underlying its formation is instrumental to unravel its striking long-distance plasticity, as shown in cases of humans born without it (Tovar-Moll et al., 2014). Using a histological approach, on the other hand, Milos Judas and his colleagues from the Croatian Institute for Brain Research tackled the significance of the cortical subplate as a transient waiting compartment in the developing brain. Situated below the developing cortex, the subplate may possibly be involved in synchronizing and amplifying a period of neurogenesis that gets longer along the evolution of primates, and in relating it with the ingrowing afferent innervation from subcortical regions. Along the same line, Eric Lewitus and his colleagues from the Max Planck Institute of Molecular Cell Biology and Genetics at Dresden, Germany, examine the role of the subventricular zone on cortical folding, characteristic of large brains. They suggest that this region placed adjacent to the earlier ventricular zone becomes more and more complex along evolution, and constrains radial processes and proliferating precursors to assume a conical organization, ending up by mechanically forcing the tissue to fold and generate gyri and sulci. Leah Krubitzer and James Dooley from the University of California at Davis, USA, take a more systemic approach: they review how the numerous functional areas of the cerebral cortex appear in evolution, related to developmental mechanisms and examples of epigenetic changes on the genome. They comment that cortical expansion follows scaling rules for the different mammalian groups, in line with what was found by Herculano-Houzel et al. (2006, 2007) for the different mammalian orders. The most important issue they tackle here is whether epigenetic influences can be incorporated into the genome and be transmitted across generations. They mention the example of maternal licking and grooming in rats, a behavior that causes increased glucocorticoid receptor transcription persistent along adult life because of a reduction in DNA methylation that can be transferred to the following generation (Kappeler and Meaney, 2010). Similar to the rat example raised by Krubitzer and Dooley, Louis Lefebvre from McGill University, Montreal, Canada, brings to scene the intriguing examples of social learning that may appear at a given individual, and then prove so useful that becomes rapidly selected by evolution to stay engrained in the species. Even more intriguingly, he reveals that the same phenomenon was observed in tits (Fisher and Hinde, 1949) and chimpanzees (Kawai, 1965): convergent evolution of high cognitive abilities? Ricardo Garcia and his collaborators from Universidad de Chile, Universidad del Desarrollo and Pontificia Universidad Catolica de Chile, tackle an even more complex cognitive ability, supposedly characteristic of humans: language. They review in detail the intricate circuits of monkey and human brains, point out similar features between them, and propose a “trajectory” for the evolution of language, from imitation of hand movements with communicative meaning, to a more complex system of manual and facial pantomimes, and finally a protospeech that opened way to full language. Finally, Michael Anderson and Barbara Finlay, from the University of Maryland and Cornell University, USA, wrap up data on brain development, plasticity and evolution, providing a deep, broad, historical review about the concept of modularity of brain organization. They also end up by questioning if brain evolution has really been made possible only by increase or decrease of modules (neurons, connections, functional regions etc.), or if, alternatively, existing basic modules are simply reused in different ways to provide diversity in animal behavior and cognitive abilities.

This article offers a conceptual framework for integrated analysis of subprocesses in action and language, based on goal-directed action. Anatomical substrates are discussed in the companion paper (Arbib and Bota, 2003) which approaches “Integrative Models of Broca's Area and the Ventral Premotor Cortex” within the context of explaining why the evolution of the human brain yielded mechanisms which support language in a multi-modal vocal-manual-facial system rather than privileging the vocal mode. Arbib and Bota (2003) examine homologies between different cortical areas in macaque and human to revisit the Mirror System Hypothesis (MSH) of Rizzolatti and Arbib (1998) — the notion that the mirror system for grasping (which has its frontal outpost in premotor area F5 of the macaque) provides the substrate for the evolution of the language-ready brain which supports parity of communication. They also offer a critique and extension based on the work of Aboitiz and Garcia (1997; Aboitiz et al., 2006). Arbib and Bota (2003) also discussed the utility of neuroinformatics in relating information across diverse cortical atlases and evaluating degrees of homology for brain regions of interest in different species (for discussion, see Deacon, 2004; Arbib and Bota, 2004).

The social complexity hypothesis posits that natural selection has favoured the evolution of intelligence in animals living in challenging social environments. Although several primate species have been shown to use information about the social relationships between conspecifics in activities such as recruiting allies or reconciling after fights, this ability to recognize third-party relationships has never been demonstrated in nonprimate mammals. However, the social complexity hypothesis predicts that nonprimates should show some of the same cognitive abilities as primates when many features of their social lives resemble those of primates. Here we tested this prediction with data from a group of free-living spotted hyaenas, Crocuta crocuta, which are gregarious carnivores that live in primate-like societies. First, we examined whether hyaenas consistently supported dominant animals over subordinates when they joined in dyadic fights. The hyaenas overwhelmingly supported the dominant animal in each fight, even when both fighting animals ranked below the supporter, and even when the dominant individual was losing the fight. Next, we examined whether hyaenas preferentially attacked relatives of their opponents after a fight. We found that they were more likely to attack relatives of their opponents after a fight than during a control period, and that they were also more likely to attack relatives of their opponents than to attack low-ranking animals unrelated to their opponents. These results suggest that hyaenas can recognize third-party relationships, and support the idea that social complexity drives the evolution of intelligence in phylogenetically disparate taxa.

Human evolution is characterized by a dramatic increase in brain size and complexity. To probe its genetic basis, we examined the evolution of genes involved in diverse aspects of nervous system biology. We found that these genes display significantly higher rates of protein evolution in primates than in rodents. Importantly, this trend is most pronounced for the subset of genes implicated in nervous system development. Moreover, within primates, the acceleration of protein evolution is most prominent in the lineage leading from ancestral primates to humans. Thus, the remarkable phenotypic evolution of the human nervous system has a salient molecular correlate, i.e., accelerated evolution of the underlying genes, particularly those linked to nervous system development. In addition to uncovering broad evolutionary trends, our study also identified many candidate genes—most of which are implicated in regulating brain size and behavior—that might have played important roles in the evolution of the human brain.

The size of human brain tripled over a period of ∼2 million years (MY) that ended 0.2–0.4 MY ago. This evolutionary expansion is believed to be important to the emergence of human language and other high-order cognitive functions, yet its genetic basis remains unknown. An evolutionary analysis of genes controlling brain development may shed light on it. ASPM (abnormal spindle-like microcephaly associated) is one of such genes, as nonsense mutations lead to primary microcephaly, a human disease characterized by a 70% reduction in brain size. Here I provide evidence suggesting that human ASPM went through an episode of accelerated sequence evolution by positive Darwinian selection after the split of humans and chimpanzees but before the separation of modern non-Africans from Africans. Because positive selection acts on a gene only when the gene function is altered and the organismal fitness is increased, my results suggest that adaptive functional modifications occurred in human ASPM and that it may be a major genetic component underlying the evolution of the human brain.

Structural genomic variations represent a major driving force of evolution and a burst of large segmental gene duplications occurred in the human lineage during its separation from non-human primates. SRGAP2, a gene recently implicated in neocortical development, has undergone two human-specific duplications. Here we find that both duplications (SRGAP2B and SRGAP2C) are partial and encode a truncated F-BAR domain. SRGAP2C is expressed in the developing and adult human brain and dimerizes with ancestral SRGAP2 to inhibit its function. In the mouse neocortex, SRGAP2 promotes spine maturation and limits spine density. Expression of SRGAP2C phenocopies SRGAP2 deficiency. It underlies sustained radial migration and leads to the emergence of human-specific features, including neoteny during spine maturation and increased density of longer spines. These results suggest that inhibition of SRGAP2 function by its human-specific paralogs has contributed to the evolution of the human neocortex and plays an important role during human brain development.

Design principles and operational modes are explored that underlie the information processing capacity of the human brain. The hypothesis is put forward that in higher organisms, especially in primates, the complexity of the neural circuitry of the cerebral cortex is the neural correlate of the brain’s coherence and predictive power, and, thus, a measure of intelligence. It will be argued that with the evolution of the human brain we have nearly reached the limits of biological intelligence.

The evolution of the human brain has been marked by a nearly 3-fold increase in size since our divergence from the last common ancestor shared with chimpanzees and bonobos. Despite increased interest in comparative neuroanatomy and phylogenetic methods, relatively little is known regarding the effects that this enlargement has had on its internal organization, and how certain areas of the brain have differentially expanded over evolutionary time. Analyses of the microstructure of several regions of the human cortex and subcortical structures have demonstrated subtle changes at the cellular and molecular level, suggesting that the human brain is more than simply a ‘scaled-up' primate brain. Ongoing research in comparative neuroanatomy has much to offer regarding our understanding of human brain evolution. Through analysis of the neuroanatomical phenotype at the level of reorganization in cytoarchitecture and cellular morphology, new data continue to highlight changes in cell density and organization associated with volumetric changes in discrete regions. An understanding of the functional significance of variation in neural circuitry can further be approached through studies of atypical human development. Many neurodevelopmental disorders cause disruption in systems associated with uniquely human features of cognition, including language and social cognition. Understanding the genetic and developmental mechanisms that underlie variation in the human cognitive phenotype can help to clarify the functional significance of interspecific variation. By uniting approaches from comparative neuroanatomy and neuropathology, insights can be gained that clarify trends in human evolution. Here, we explore these lines of evidence and their significance for understanding functional variation between species as well as within neuropathological variation in the human brain.