The evolution of brain neuron numbers in amniotes.

SignificanceThe evolution of brain processing capacity has traditionally been inferred from data on brain size. However, similarly sized brains of distantly related species can differ in the number and distribution of neurons, their basic computational units. Therefore, a finer-grained approach is needed to reveal the evolutionary paths to increased cognitive capacity. Using a new, comprehensive dataset, we analyzed brain cellular composition across amniotes. Compared to reptiles, mammals and birds have dramatically increased neuron numbers in the telencephalon and cerebellum, which are brain parts associated with higher cognition. Astoundingly, a phylogenetic analysis suggests that as few as four major changes in neuron-brain scaling in over 300 million years of evolution pave the way to intelligence in endothermic land vertebrates.

Smarter foragers do not forage smarter: a test of the diet hypothesis for brain expansion.

A leading hypothesis for the evolution of large brains in humans and other species is that a feedback loop exists whereby intelligent animals forage more efficiently, which results in increased energy intake that fuels the growth and maintenance of large brains. We test this hypothesis for the first time with high-resolution tracking data from four sympatric, frugivorous rainforest mammal species (42 individuals) and drone-based maps of their predominant feeding trees. We found no evidence that larger-brained primates had more efficient foraging paths than smaller brained procyonids. This refutes a key assumption of the fruit-diet hypothesis for brain evolution, suggesting that other factors such as temporal cognition, extractive foraging or sociality have been more important for brain evolution.

Turbidity drives plasticity in the eyes and brains of an African cichlid.

Natural variation in environmental turbidity correlates with variation in the visual sensory system of many fishes, suggesting that turbidity may act as a strong selective agent on visual systems. Since many aquatic systems experience increased turbidity due to anthropogenic perturbations, it is important to understand the degree to which fish can respond to rapid shifts in their visual environment, and whether such responses can occur within the lifetime of an individual. We examined whether developmental exposure to turbidity (clear, <5 NTU; turbid, ∼9 NTU) influenced the size of morphological structures associated with vision in the African blue-lip cichlid Pseudocrenilabrus multicolor. Parental fish were collected from two sites (clear swamp, turbid river) in western Uganda. F1 broods from each population were split and reared under clear and turbid rearing treatments until maturity. We measured morphological traits associated with the visual sensory system (eye diameter, pupil diameter, axial length, brain mass, optic tectum volume) over the course of development. Age was significant in explaining variation in visual traits even when standardized for body size, suggesting an ontogenetic shift in the relative size of eyes and brains. When age groups were analyzed separately, young fish reared in turbid water grew larger eyes than fish reared in clear conditions. Population was important in the older age category, with swamp-origin fish having relatively larger eyes and optic lobes relative to river-origin fish. Plastic responses during development may be important for coping with a more variable visual environment associated with anthropogenically induced turbidity.

Evolutionary lability of food caching behaviour in mammals.

Food hoarding provides animals access to resources during periods of scarcity. Studies on mammalian caching indicate associations with brain size, seasonality and diet but are biased to a subset of rodents. Whether the behaviour is generalizable at other taxonomic scales and/or is influenced by other ecological factors is less understood. Population density may influence food caching due to food competition or pilferage, but this remains untested in a comparative framework. Using phylogenetic analyses, we assessed the role of morphology (body and brain size), climate, diet breadth and population density on food caching behaviour evolution at multiple taxonomic scales. We also used a long-term dataset on caching behaviour of red squirrels (Tamiasciurus fremonti) to test key factors (climate and population density) on hoarding intensity. Consistent with previous smaller scale studies, we found the mammalian ancestral state for food caching was larderhoarding, and scatterhoarding was derived. Caching strategy was strongly associated with brain size, population density and climate. Mammals with larger brains and hippocampal volumes were more likely to scatterhoard, and species living at higher population densities and in colder climates were more likely to larderhoard. Finer-scale analyses within families, sub-families and tribes indicated that the behaviour is evolutionary labile. Brain size in family Sciuridae and tribe Marmotini was larger in scatterhoarders, but not in other tribes. Scatterhoarding in tribe Marmotini was more likely in species with lower population densities while scatterhoarding in tribe Sciurini was associated with warmer climates. Red squirrel larderhoarding intensity was positively related to population density but not climate, implicating food competition or pilferage as an important mechanism mediating caching behaviour. Our results are consistent with previous smaller-scale studies on food caching and indicate the evolutionary patterns of mammalian food caching are broadly generalizable. Given the lability of caching behaviour as evidenced by the variability of our results at finer phylogenetic scales, comparative analyses must consider taxonomic scale. Applying our results to conservation could prove useful as changes in population density or climate may select for different food caching strategies and thus can inform management of threatened and endangered species and their habitats.

The reduction in relative brain size in the domesticated dog is not an evolutionary singularity among the canids.

Domestication has long been considered the most powerful evolutionary engine behind dramatic reductions in brain size in several taxa, and the dog (Canis familiaris) is considered as a typical example that shows a substantial decrease in brain size relative to its ancestor, the grey wolf (Canis lupus). However, to make the case for exceptional evolution of reduced brain size under domestication requires an interspecific approach in a phylogenetic context that can quantify the extent by which domestication reduces brain size in comparison to closely related non-domesticated species responding to different selection factors in the wild. Here, we used a phylogenetic method to identify evolutionary singularities to test if the domesticated dog stands out in terms of relative brain size from other species of canids. We found that the dog does not present unambiguous signature of evolutionary singularity with regard to its small brain size, as the results were sensitive to the considerations about the ancestral trait values upon domestication. However, we obtained strong evidence for the hibernating common raccoon dog (Nyctereutes procyonoides) being an evolutionary outlier for its brain size. Therefore, domestication is not necessarily an exceptional case concerning evolutionary reductions in brain size in an interspecific perspective.

The genomics of ecological flexibility, large brains, and long lives in capuchin monkeys revealed with fecalFACS.

Ecological flexibility, extended lifespans, and large brains have long intrigued evolutionary biologists, and comparative genomics offers an efficient and effective tool for generating new insights into the evolution of such traits. Studies of capuchin monkeys are particularly well situated to shed light on the selective pressures and genetic underpinnings of local adaptation to diverse habitats, longevity, and brain development. Distributed widely across Central and South America, they are inventive and extractive foragers, known for their sensorimotor intelligence. Capuchins have among the largest relative brain size of any monkey and a lifespan that exceeds 50 y, despite their small (3 to 5 kg) body size. We assemble and annotate a de novo reference genome for Cebus imitator Through high-depth sequencing of DNA derived from blood, various tissues, and feces via fluorescence-activated cell sorting (fecalFACS) to isolate monkey epithelial cells, we compared genomes of capuchin populations from tropical dry forests and lowland rainforests and identified population divergence in genes involved in water balance, kidney function, and metabolism. Through a comparative genomics approach spanning a wide diversity of mammals, we identified genes under positive selection associated with longevity and brain development. Additionally, we provide a technological advancement in the use of noninvasive genomics for studies of free-ranging mammals. Our intra- and interspecific comparative study of capuchin genomics provides insights into processes underlying local adaptation to diverse and physiologically challenging environments, as well as the molecular basis of brain evolution and longevity.

Callosal Fiber Length Scales with Brain Size According to Functional Lateralization, Evolution, and Development.

Brain size significantly impacts the organization of white matter fibers. Fiber length scaling, the degree to which fiber length varies according to brain size, was overlooked. We investigated how fiber lengths within the corpus callosum, the most prominent white matter tract, vary according to brain size. The results showed substantial variation in length scaling among callosal fibers, replicated in two large healthy cohorts (∼2000 human subjects, including both sexes). The underscaled callosal fibers mainly connected the precentral gyrus and parietal cortices, whereas the overscaled callosal fibers mainly connected the prefrontal cortices. The variation in such length scaling was biologically meaningful: larger scaling corresponded to larger neurite density index but smaller fractional anisotropy values; cortical regions connected by the callosal fibers with larger scaling were more lateralized functionally as well as phylogenetically and ontogenetically more recent than their counterparts. These findings highlight an interaction between interhemispheric communication and organizational and adaptive principles underlying brain development and evolution.SIGNIFICANCE STATEMENT Brain size varies across evolution, development, and individuals. Relative to small brains, the neural fiber length in large brains is inevitably increased, but the degree of such increase may differ between fiber tracts. Such a difference, if it exists, is valuable for understanding adaptive neural principles in large versus small brains during evolution and development. The present study showed a substantial difference in the length increase between the callosal fibers that connect the two hemispheres, replicated in two large healthy cohorts. Together, our study demonstrates that reorganization of interhemispheric fibers length according to brain size is intrinsically related to fiber composition, functional lateralization, cortical myelin content, and evolutionary and developmental expansion.

Transplant experiments demonstrate that larger brains are favoured in high-competition environments in Trinidadian killifish.

The extent to which the evolution of a larger brain is adaptive remains controversial. Trinidadian killifish (Anablepsoides hartii) are found in sites that differ in predation intensity; fish that experience decreased predation and increased intraspecific competition exhibit larger brains. We evaluated the connection between brain size and fitness (survival and growth) when killifish are found in their native habitats and when fish are transplanted from sites with predators to high-competition sites that lack predators. Selection for a larger brain was absent within locally adapted populations. Conversely, there was a strong positive relationship between brain size and growth in transplanted but not resident fish in high-competition environments. We also observed significantly larger brain sizes in the transplanted fish that were recaptured at the end of the experiment versus those that were not. Our results provide experimental support that larger brains increase fitness and are favoured in high-competition environments.

Both brain size and biological sex contribute to variation in white matter microstructure in middle-aged healthy adults.

Whether head size and/or biological sex influence proxies of white matter (WM) microstructure such as fractional anisotropy (FA) and mean diffusivity (MD) remains controversial. Diffusion tensor imaging (DTI) indices are also associated with age, but there are large discrepancies in the spatial distribution and timeline of age-related differences reported. The aim of this study was to evaluate the associations between intracranial volume (ICV), sex, and age and DTI indices from WM in a population-based study of healthy individuals (n = 812) aged 50-66 in the Nord-Trøndelag health survey. Semiautomated tractography and tract-based spatial statistics (TBSS) analyses were performed on the entire sample and in an ICV-matched sample of men and women. The tractography results showed a similar positive association between ICV and FA in all major WM tracts in men and women. Associations between ICV and MD, radial diffusivity and axial diffusivity were also found, but to a lesser extent than FA. The TBSS results showed that both men and women had areas of higher and lower FA when controlling for age, but after controlling for age and ICV only women had areas with higher FA. The ICV matched analysis also demonstrated that only women had areas of higher FA. Age was negatively associated with FA across the entire WM skeleton in the TBSS analysis, independent of both sex and ICV. Combined, these findings demonstrated that both ICV and sex contributed to variation in DTI indices and emphasized the importance of considering ICV as a covariate in DTI analysis.

Sociality, ecology and developmental constraints predict variation in brain size across birds.

Conflicting theories have been proposed to explain variation in relative brain size across the animal kingdom. Ecological theories argue that the cognitive demands of seasonal or unpredictable environments have selected for increases in relative brain size, whereas the 'social brain hypothesis' argues that social complexity is the primary driver of brain size evolution. Here, we use a comparative approach to test the relative importance of ecology (diet, foraging niche and migration), sociality (social bond, cooperative breeding and territoriality) and developmental mode in shaping brain size across 1886 bird species. Across all birds, we find a highly significant effect of developmental mode and foraging niche on brain size, suggesting that developmental constraints and selection for complex motor skills whilst foraging generally imposes important selection on brain size in birds. We also find effects of social bonding and territoriality on brain size, but the direction of these effects do not support the social brain hypothesis. At the same time, we find extensive heterogeneity among major avian clades in the relative importance of different variables, implying that the significance of particular ecological and social factors for driving brain size evolution is often clade- and context-specific. Overall, our results reveal the important and complex ways in which ecological and social selection pressures and developmental constraints shape brain size evolution across birds.

Adding the neuro to cognition: from food storing to nest building.

Typically, investigations of animal cognition couple careful experimental manipulations with examination of the animal's behavioural responses. Sometimes those questions have included attempts to describe the neural underpinnings of the behavioural outputs. Over the past 25 years, behaviours that involve spatial learning and memory (such as navigation and food storing) has been one context in which such dual or correlated investigations have been both accessible and productive. Here I review some of that work and where it has led. Because of the wealth of data and insights gained from that work and song learning before it, it seems that it might also be useful to try to add some neurobiology to other systems in animal cognition. I finish then, with a description of recent work on the cognition and neurobiology of avian nest building. It is still relatively early days but asking questions about the cognition of nest building has already shown both neural correlates of nest building and that learning and memory play a much greater role in this behaviour than previously considered. While it is not yet clear how putting these components together will be synergistic, the examples of song learning and food storing provide encouragement. Perhaps this might be true for other behaviours too?

Brain size predicts bees' tolerance to urban environments.

The rapid conversion of natural habitats to anthropogenic landscapes is threatening insect pollinators worldwide, raising concern regarding the negative consequences on their fundamental role as plant pollinators. However, not all pollinators are negatively affected by habitat conversion, as certain species find appropriate resources in anthropogenic landscapes to persist and proliferate. The reason why some species tolerate anthropogenic environments while most find them inhospitable remains poorly understood. The cognitive buffer hypothesis, widely supported in vertebrates but untested in insects, offers a potential explanation. This theory suggests that species with larger brains have enhanced behavioural plasticity, enabling them to confront and adapt to novel challenges. To investigate this hypothesis in insects, we measured brain size for 89 bee species, and evaluated their association with the degree of habitat occupancy. Our analyses revealed that bee species mainly found in urban habitats had larger brains relative to their body size than those that tend to occur in forested or agricultural habitats. Additionally, urban bees exhibited larger body sizes and, consequently, larger absolute brain sizes. Our results provide the first empirical support for the cognitive buffer hypothesis in invertebrates, suggesting that a large brain in bees could confer behavioural advantages to tolerate urban environments.

Connecting the Pipes: Agricultural Tile Drains and Elevated Imidacloprid Brain Concentrations in Juvenile Northern Leopard Frogs (Rana pipiens).

Neonicotinoids are neurotoxic insecticides and are often released into nearby wetlands via subsurface tile drains and can negatively impact nontarget organisms, such as amphibians. Previous studies have indicated that imidacloprid, a commonly used neonicotinoid, can cross the amphibian blood-brain barrier under laboratory conditions; however, little is known about the impact of low concentrations in a field-based setting. Here, we report aqueous pesticide concentrations at wetland production areas that were either connected or not connected to agricultural tile drains, quantified imidacloprid and its break down products in juvenile amphibian brains and livers, and investigated the relationship between imidacloprid brain concentration and brain size. Imidacloprid concentrations in brain and water samples were nearly 2.5 and 5 times higher at tile wetlands (brain = 4.12 ± 1.92 pg/mg protein; water = 0.032 ± 0.045 µg/L) compared to reference wetlands, respectively. Tile wetland amphibians also had shorter cerebellums (0.013 ± 0.001 mm), depicting a negative relationship between imidacloprid brain concentration and cerebellum length. The metabolite, desnitro-imidacloprid, had liver concentrations that were 2 times higher at tile wetlands (2 ± 0.3 µg/g). Our results demonstrate that imidacloprid can cross the amphibian blood-brain barrier under ecological conditions and may alter brain dimensions and provide insight into the metabolism of imidacloprid in amphibians.

Climate Change Influences Brain Size in Humans.

Brain size evolution in hominins constitutes a crucial evolutionary trend, yet the underlying mechanisms behind those changes are not well understood. Here, climate change is considered as an environmental factor using multiple paleoclimate records testing temperature, humidity, and precipitation against changes to brain size in 298 Homo specimens over the past fifty thousand years. Across regional and global paleoclimate records, brain size in Homo averaged significantly lower during periods of climate warming as compared to cooler periods. Geological epochs displayed similar patterns, with Holocene warming periods comprising significantly smaller brained individuals as compared to those living during glacial periods at the end of the Late Pleistocene. Testing spatiotemporal patterns, the adaptive response appears to have started roughly fifteen thousand years ago and may persist into modern times. To a smaller degree, humidity and precipitation levels were also predictive of brain size, with arid periods associated with greater brain size in Homo. The findings suggest an adaptive response to climate change in human brain size that is driven by natural selection in response to environmental stress.

Hippocampal, Whole Midbrain, Red Nucleus, and Ventral Tegmental Area Volumes Are Increased by Selective Breeding for High Voluntary Wheel-Running Behavior.

Uncovering relationships between neuroanatomy, behavior, and evolution are important for understanding the factors that control brain function. Voluntary exercise is one key behavior that both affects, and may be affected by, neuroanatomical variation. Moreover, recent studies suggest an important role for physical activity in brain evolution. We used a unique and ongoing artificial selection model in which mice are bred for high voluntary wheel-running behavior, yielding four replicate lines of high runner (HR) mice that run ∼3-fold more revolutions per day than four replicate nonselected control (C) lines. Previous studies reported that, with body mass as a covariate, HR mice had heavier whole brains, non-cerebellar brains, and larger midbrains than C mice. We sampled mice from generation 66 and used high-resolution microscopy to test the hypothesis that HR mice have greater volumes and/or cell densities in nine key regions from either the midbrain or limbic system. In addition, half of the mice were given 10 weeks of wheel access from weaning, and we predicted that chronic exercise would increase the volumes of the examined brain regions via phenotypic plasticity. We replicated findings that both selective breeding and wheel access increased total brain mass, with no significant interaction between the two factors. In HR compared to C mice, adjusting for body mass, both the red nucleus (RN) of the midbrain and the hippocampus (HPC) were significantly larger, and the whole midbrain tended to be larger, with no effect of wheel access nor any interactions. Linetype and wheel access had an interactive effect on the volume of the periaqueductal gray (PAG), such that wheel access increased PAG volume in C mice but decreased volume in HR mice. Neither linetype nor wheel access affected volumes of the substantia nigra, ventral tegmental area, nucleus accumbens, ventral pallidum (VP), or basolateral amygdala. We found no main effect of either linetype or wheel access on neuronal densities (numbers of cells per unit area) for any of the regions examined. Taken together, our results suggest that the increased exercise phenotype of HR mice is related to increased RN and hippocampal volumes, but that chronic exercise alone does not produce such phenotypes.

Phenotypic responses to climate change are significantly dampened in big-brained birds.

Anthropogenic climate change is rapidly altering local environments and threatening biodiversity throughout the world. Although many wildlife responses to this phenomenon appear largely idiosyncratic, a wealth of basic research on this topic is enabling the identification of general patterns across taxa. Here, we expand those efforts by investigating how avian responses to climate change are affected by the ability to cope with ecological variation through behavioural flexibility (as measured by relative brain size). After accounting for the effects of phylogenetic uncertainty and interspecific variation in adaptive potential, we confirm that although climate warming is generally correlated with major body size reductions in North American migrants, these responses are significantly weaker in species with larger relative brain sizes. Our findings suggest that cognition can play an important role in organismal responses to global change by actively buffering individuals from the environmental effects of warming temperatures.

A Positively Selected MAGEE2 LoF Allele Is Associated with Sexual Dimorphism in Human Brain Size and Shows Similar Phenotypes in Magee2 Null Mice.

A nonsense allele at rs1343879 in human MAGEE2 on chromosome X has previously been reported as a strong candidate for positive selection in East Asia. This premature stop codon causing ∼80% protein truncation is characterized by a striking geographical pattern of high population differentiation: common in Asia and the Americas (up to 84% in the 1000 Genomes Project East Asians) but rare elsewhere. Here, we generated a Magee2 mouse knockout mimicking the human loss-of-function mutation to study its functional consequences. The Magee2 null mice did not exhibit gross abnormalities apart from enlarged brain structures (13% increased total brain area, P = 0.0022) in hemizygous males. The area of the granular retrosplenial cortex responsible for memory, navigation, and spatial information processing was the most severely affected, exhibiting an enlargement of 34% (P = 3.4×10-6). The brain size in homozygous females showed the opposite trend of reduced brain size, although this did not reach statistical significance. With these insights, we performed human association analyses between brain size measurements and rs1343879 genotypes in 141 Chinese volunteers with brain MRI scans, replicating the sexual dimorphism seen in the knockout mouse model. The derived stop gain allele was significantly associated with a larger volume of gray matter in males (P = 0.00094), and smaller volumes of gray (P = 0.00021) and white (P = 0.0015) matter in females. It is unclear whether or not the observed neuroanatomical phenotypes affect behavior or cognition, but it might have been the driving force underlying the positive selection in humans.

Allometry in the corpus callosum in neonates: Sexual dimorphism.

The corpus callosum (CC) is the largest fiber tract in the human brain, allowing interhemispheric communication by connecting homologous areas of the two cerebral hemispheres. In adults, CC size shows a robust allometric relationship with brain size, with larger brains having larger callosa, but smaller brains having larger callosa relative to brain size. Such an allometric relationship has been shown in both males and females, with no significant difference between the sexes. But there is some evidence that there are alterations in these allometric relationships during development. However, it is currently not known whether there is sexual dimorphism in these allometric relationships from birth, or if it only develops later. We study this in neonate data. Our results indicate that there are already sex differences in these allometric relationships in neonates: male neonates show the adult-like allometric relationship between CC size and brain size; however female neonates show a significantly more positive allometry between CC size and brain size than either male neonates or female adults. The underlying cause of this sexual dimorphism is unclear; but the existence of this sexual dimorphism in neonates suggests that sex-differences in lateralization have prenatal origins.

Evolutionary divergence in phenotypic plasticity shapes brain size variation between coexisting sunfish ecotypes.

Mechanisms that generate brain size variation and the consequences of such variation on ecological performance are poorly understood in most natural animal populations. We use a reciprocal-transplant common garden experiment and foraging performance trials to test for brain size plasticity and the functional consequences of brain size variation in Pumpkinseed sunfish (Lepomis gibbosus) ecotypes that have diverged between nearshore littoral and offshore pelagic lake habitats. Different age-classes of wild-caught juveniles from both habitats were exposed for 6 months to treatments that mimicked littoral and pelagic foraging. Plastic responses in oral jaw size suggested that treatments mimicked natural habitat-specific foraging conditions. Plastic brain size responses to foraging manipulations differed between ecotypes, as only pelagic sourced fish showed brain size plasticity. Only pelagic juveniles under 1 year-old expressed this plastic response, suggesting that plastic brain size responses decline with age and so may be irreversible. Finally, larger brain size was associated with enhanced foraging performance on live benthic but not pelagic prey, providing the first experimental evidence of a relationship between brain size and prey-specific foraging performance in fishes. The recent post-glacial origin of these ecotypes suggests that brain size plasticity can rapidly evolve and diverge in fish under contrasting ecological conditions.

The costs and benefits of larger brains in fishes.

The astonishing diversity of brain sizes observed across the animal kingdom is typically explained in the context of trade-offs: the benefits of a larger brain, such as enhanced cognitive ability, are balanced against potential costs, such as increased energetic demands. Several hypotheses have been formulated in this framework, placing different emphasis on ecological, behavioural, or physiological aspects of trade-offs in brain size evolution. Within this body of work, there exists considerable taxonomic bias towards studies of birds and mammals, leaving some uncertainty about the generality of the respective arguments. Here, we test three of the most prominent such hypotheses, the 'expensive tissue', 'social brain' and 'cognitive buffer' hypotheses, in a large dataset of fishes, derived from a publicly available resource (FishBase). In accordance with predictions from the 'expensive tissue' and the 'social brain' hypothesis, larger brains co-occur with reduced fecundity and increased sociality in at least some Classes of fish. Contrary to expectations, however, lifespan is reduced in large-brained fishes, and there is a tendency for species that perform parental care to have smaller brains. As such, it appears that some potential costs (reduced fecundity) and benefits (increased sociality) of large brains are near universal to vertebrates, whereas others have more lineage-specific effects. We discuss our findings in the context of fundamental differences between the classically studied birds and mammals and the fishes we analyse here, namely divergent patterns of growth, parenting and neurogenesis. As such, our work highlights the need for a taxonomically diverse approach to any fundamental question in evolutionary biology.