Brain growth in modern humans using multiple developmental databases.

In this review we attempt to reconstruct the evolutionary history of hominin life history from extant and fossil evidence. We utilize demographic life history theory and distinguish life history variables, traits such as weaning, age at sexual maturity, and life span, from life history-related variables such as body mass, brain growth, and dental development. The latter are either linked with, or can be used to make inferences about, life history, thus providing an opportunity for estimating life history parameters in fossil taxa. We compare the life history variables of modern great apes and identify traits that are likely to be shared by the last common ancestor of Pan-Homo and those likely to be derived in hominins. All great apes exhibit slow life histories and we infer this to be true of the last common ancestor of Pan-Homo and the stem hominin. Modern human life histories are even slower, exhibiting distinctively long post-menopausal life spans and later ages at maturity, pointing to a reduction in adult mortality since the Pan-Homo split. We suggest that lower adult mortality, distinctively short interbirth intervals, and early weaning characteristic of modern humans are derived features resulting from cooperative breeding. We evaluate the fidelity of three life history-related variables, body mass, brain growth and dental development, with the life history parameters of living great apes. We found that body mass is the best predictor of great ape life history events. Brain growth trajectories and dental development and eruption are weakly related proxies and inferences from them should be made with caution. We evaluate the evidence of life history-related variables available for extinct species and find that prior to the transitional hominins there is no evidence of any hominin taxon possessing a body size, brain size or aspects of dental development much different from what we assume to be the primitive life history pattern for the Pan-Homo clade. Data for life history-related variables among the transitional hominin grade are consistent and none agrees with a modern human pattern. Aside from mean body mass, adult brain size, crown and root formation times, and the timing and sequence of dental eruption of Homo erectus are inconsistent with that of modern humans. Homo antecessor fossil material suggests a brain size similar to that of Homo erectus s. s., and crown formation times that are not yet modern, though there is some evidence of modern human-like timing of tooth formation and eruption. The body sizes, brain sizes, and dental development of Homo heidelbergensis and Homo neanderthalensis are consistent with a modern human life history but samples are too small to be certain that they have life histories within the modern human range. As more life history-related variable information for hominin species accumulates we are discovering that they can also have distinctive life histories that do not conform to any living model. At least one extinct hominin subclade, Paranthropus, has a pattern of dental life history-related variables that most likely set it apart from the life histories of both modern humans and chimpanzees.

The evaluation of hydrocephalus remains focused on ventricular size, yet the goal of treatment is to allow for healthy brain development. It is likely that brain volume is more related to cognitive development than is fluid volume in children with hydrocephalus. This study tests this hypothesis by comparing brain and fluid volumes with neurocognitive outcome in pediatric patients with hydrocephalus. Warf and colleagues previously acquired CT scans for pediatric patients in Uganda with myelomeningocele, measured frontal-occipital horn ratio (FOHR), and administered the modified Bayley Scales of Infant Development, third edition (BSID-III) to measure neurocognitive outcome that did not correlate with FOHR. In this present study, brain and fluid volumes were measured in 33 of these patients, 26 of whom required surgical treatment for hydrocephalus. Linear discrimination analysis (LDA) was used to test whether age-normalized brain and fluid volumes can discriminate neurocognitive outcome. Hydrocephalic patients show normal to small brain volumes and substantially larger fluid volumes compared with normal values. FOHR correlates highly with fluid volume (r=0.84, p<0.001) and substantially less with brain volume (r=-0.37, p=0.03), while brain and fluid volumes do not correlate with each other (p=0.99). Brain and CSF volumes correlated best with fine motor (p=0.03, p=0.01), cognitive (p=0.05, p=0.09), and expressive communication (p=0.08, p=0.08) scores. A combination of these 3 scores was used as a multivariate measure of neurocognitive outcome. Brain volume alone, unlike fluid volume, could discriminate high from low cognitive outcome (by t-test and ANOVA). It was shown that a combination of age-normalized brain and fluid volumes can discriminate neurocognitive outcome by 2-way LDA (p<0.01) and 3-way LDA (p<0.01). The multivariate LDA demonstrated the contribution of large fluid volume to a decrement in cognition. Hydrocephalus is treated by normalizing CSF, but normal brain development depends on brain growth. A combination of brain and CSF volumes appears to be significantly more powerful at predicting good versus poor neurocognitive outcomes in patients with hydrocephalus than either volume alone.

Sex and species differences in mouse and rat forebrain commissures depend on the method of adjusting for brain size

Expansion of the human brain, and specifically the neocortex, is among the most remarkable evolutionary processes that correlates with cognitive, emotional, and social abilities. Cortical expansion is determined through a tightly orchestrated process of neural stem cell proliferation, migration, and ongoing organization, synaptogenesis, and apoptosis. Perturbations of each of these intricate steps can lead to abnormalities of brain size in humans, whether small (microcephaly) or large (megalencephaly). Abnormalities of brain growth can be clinically isolated or occur as part of complex syndromes associated with other neurodevelopmental problems (eg, epilepsy, autism, intellectual disability), brain malformations, and body growth abnormalities. Thorough review of the genetic literature reveals that human microcephaly and megalencephaly are caused by mutations of a rapidly growing number of genes linked within critical cellular pathways that impact early brain development, with important pathomechanistic links to cancer, body growth, and epilepsy. Given the rapid rate of causal gene identification for microcephaly and megalencephaly understanding the roles and interplay of these important signaling pathways is crucial to further unravel the mechanisms underlying brain growth disorders and, more fundamentally, normal brain growth and development in humans. In this review, we will (a) overview the definitions of microcephaly and megalencephaly, highlighting their classifications in clinical practice; (b) overview the most common genes and pathways underlying microcephaly and megalencephaly based on the fundamental cellular processes that are perturbed during cortical development; and (c) outline general clinical molecular diagnostic workflows for children and adults presenting with microcephaly and megalencephaly.

We investigated the relationship between body size, brain size, and fibers in selected cranial nerves in shrews and moles. Species include tiny masked shrews (S. cinereus) weighing only a few grams and much larger mole species weighing up to 90 grams. It also includes closely related species with very different sensory specializations – such as the star-nosed mole and the common, eastern mole. We found that moles and shrews have tiny optic nerves with fiber counts not correlated with body or brain size. Auditory nerves were similarly small but increased in fiber number with increasing brain and body size. Trigeminal nerve number was by far the largest and also increased with increasing brain and body size. The star-nosed mole was an outlier, with more than twice the number of trigeminal nerve fibers than any other species. Despite this hypertrophied cranial nerve, star-nosed mole brains were not larger than predicted from body size, suggesting that magnification of their somatosensory systems does not result in greater overall CNS size.

1. The hominid brain has increased approximately three times in size since the Pliocene, but so has the brain of equids. The tripling of hominid brain size has been considered as an indicator of increased mental abilities, as it coincided with the production of tools, weapons and other artefacts of increasing sophistication. No indicators of the increase in equid intelligence are known. Intraspecific correlation between brain size and variously measured 'intelligence' is, in modern humans, very weak if not completely absent. With the exception of size, there are no major differences between the anatomy of ape and human brains. 2. A study of 297 estimates of body height, 626 estimates of bodyweight and 276 estimates of the cranial capacity of hominids dated at various periods over the past 5 million years shows that the increase in hominid brain size was paralleled by an increase in body size. 3. In a sample of 45 variously dated fossil hominids, brain size correlates isometrically with body size. 4. Since the Late Pleistocene (approximately 30,000 years ago), human brain size decreased by approximately 10%; yet again, this decrease was paralleled by a decrease in body size. 5. Therefore, it may be concluded that the gross anatomy of the hominid brain is not related to its functional capabilities. The large human brain:body size ratio may be a result of the structural reduction of the size of the gastrointestinal tract and, consequently, its musculoskeletal supports. It is related to richer, meat-based diets and extra-oral food processing rather than the exceptional increase in the size of the cerebrum. The exceptional mental abilities of humans may be a result of functional rather than anatomical evolution.

The cerebellum contains most of the neurons in the human brain, and exhibits unique modes of development, malformation, and aging. For example, granule cells—the most abundant neuron type—develop unusually late and exhibit unique nuclear morphology. Here, by developing our high-resolution single-cell 3D genome assay Dip-C into population-scale (Pop-C) and virus-enriched (vDip-C) modes, we were able to resolve the first 3D genome structures of single cerebellar cells, create life-spanning 3D genome atlases for both human and mouse, and jointly measure transcriptome and chromatin accessibility during development. We found that while the transcriptome and chromatin accessibility of human granule cells exhibit a characteristic maturation pattern within the first year of postnatal life, 3D genome architecture gradually remodels throughout life into a non-neuronal state with ultra-long-range intra-chromosomal contacts and specific inter-chromosomal contacts. This 3D genome remodeling is conserved in mice, and robust to heterozygous deletion of chromatin remodeling disease-associated genes (Chd8 or Arid1b). Together these results reveal unexpected and evolutionarily-conserved molecular processes underlying the unique development and aging of the mammalian cerebellum.

Changes in body proportions over the first year of life: comparisons between ‘light-for-dates’ and ‘appropriate-for-dates’ term infants

Extract: The serum levels of free amino acids have been investigated during the first year of postnatal life in the rhesus monkey (M. mulatta). Samples of umbilical vein blood were obtained following normal full-term pregnancies. Infant monkeys were fed Similac®, a proprietary milk formulation with constant amino acid composition, at four-hour intervals throughout the first year of life. Blood samples were obtained at 2 weeks and at 1, 3, 6, 9 and 12 months of age, and the serum analyzed for all free amino acids. A wide range of values was evident for each amino acid at each age studied (table I). When all values obtained for each amino acid during the entire first year were analyzed, however, it was apparent that taurine, lysine, and 3-methyl-histidine were significantly elevated, and serine, tyrosine, and leucine were significantly reduced in the umbilical vein samples. By the end of the first month of life, values for all amino acids were within the normal range for adolescent and nonpregnant adult animals; further significant changes in amino acid levels did not occur during the remainder of the year of study. Speculation: The nutritional correlates of growth and development in most laboratory animals are sufficiently different from those in the human to question their use in studies related to human nutrition. This study demonstrates that the patterns of change in the free amino acids of serum in the infant rhesus monkey are generally comparable to those observed in the human infant, and indicates that this species may be a suitable experimental counterpart for investigations of protein and amino acid metabolism which cannot be performed in children.

Teratology is the science that investigates the congenital malformations and their causes Intrauterine exposure to a toxicant particularly in early pregnancy induces embryonic and fetal changes ranging from none up to malformations and stillbirths The teratogenic agents include some viral spirochetal and protozoal infections physical agents as ionizing radiations and excessive heat pharmacological drugs as thalidomide excessive vitamin A corticosteroids antiepileptic antimalarial antileishmaniasis and antihypertensive agents industrial pollutants as toluene and cadmium alcohol and smoking abuse and narcotics Maternal health problems as diabetes mellitus multiple sclerosis and rheumatoid arthritis may also add to the etiology list of teratogenesis The prevalence of the congenital birth defects ranges from to throughout the first year of postnatal life

Myrtle McGraw's Unrecognized Conceptual Contribution to Developmental Psychology

The relationship between brain size and body size across species “from mouse to elephant” is described by a function of positive slope. Almost uniformly, the relationship between brain size and body size within a species has a positive slope, though this is less steep than across species. The spotted hyena, Crocuta crocuta, differs from most other mammals in a number of ways including the fact that, on average, adult females weigh more than adult males and occasionally display greater body lengths. Brains of 5 female and 4 male hyenas were weighed in the field near Moyale in Northern Kenya, and body weights and body lengths were obtained from the same animals. When our analyses of brain/body relationships in these animals revealed an unanticipated negative relationship between brain size and body length, we extended our measurements to include intracranial volume in 19 skulls (8 females and 11 males) from the collection at the Museum of Vertebrate Zoology, University of California Berkeley; body weights and lengths were also available. A third dataset was formed by measuring intracranial volumes in 60 spotted hyena skulls (27 females and 33 males) in the Natural History Museum, London, UK; body lengths and intracranial volumes were available. Brain/body size slopes, in general, were not significantly different from zero except in 3 cases: brain weight/body length for Moyale males alone and males and females together, and cranial volume/body weight for Museum of Vertebrate Zoology males and females together. Although most of the slopes were not significantly different from zero, they were all negative, and a statistical test which combined probabilities from the 3 datasets supports the conclusion that there is a negative relationship between brain size and body size in spotted hyenas. Possible explanations for the negative slopes are discussed, including costs and benefits of large brains and large bodies and physiological mechanisms.

Magnetic resonance imaging was used to evaluate the influence of sex and brain size on compartmental brain volumes (grey matter, white matter, CSF) in a large and well-matched sample of neurologically normal women (n = 50) and men (n = 50). As expected, we found a significant sex difference for the absolute volumes of total brain, grey matter, white matter and CSF, with greater volumes for men. Relating these compartmental volume measures to brain volume resulting in proportional volume measures revealed a higher proportion of grey matter in women. No significant sex differences were found for white matter and CSF proportions. However, when the influence of sex was partialized out by regression analyses, brain volume explained 40-81% of the variance of the absolute grey matter, white matter and CSF volumes. Performing these regression analyses for the proportional volume measures revealed that brain volume explained approximately 16% of the variance in grey matter proportion. Sex or the interaction between sex and brain volume revealed no additional predicitve values. Interestingly, the correlation between brain volume and grey matter proportion was negative, with larger brains exhibiting relatively smaller proportions of grey matter. Thus, sex is not the main variable explaining the variability in grey matter volume. Rather, we suggest that brain size is the main variable determining the proportion of grey matter.

Considerable controversy exists about which hypotheses and variables best explain mammalian brain size variation. We use a new, high-coverage dataset of marsupial brain and body sizes, and the first phylogenetically imputed full datasets of 16 predictor variables, to model the prevalent hypotheses explaining brain size evolution using phylogenetically corrected Bayesian generalized linear mixed-effects modelling. Despite this comprehensive analysis, litter size emerges as the only significant predictor. Marsupials differ from the more frequently studied placentals in displaying a much lower diversity of reproductive traits, which are known to interact extensively with many behavioural and ecological predictors of brain size. Our results therefore suggest that studies of relative brain size evolution in placental mammals may require targeted co-analysis or adjustment of reproductive parameters like litter size, weaning age or gestation length. This supports suggestions that significant associations between behavioural or ecological variables with relative brain size may be due to a confounding influence of the extensive reproductive diversity of placental mammals.

Because brains do not fossilize, the internal surface of the braincase (endocast) serves as an important source of information about brain growth, development, and evolution. Recent studies of endocranial morphology and development in great apes, fossil hominins, and modern humans have revealed taxon-specific differences. However, it remains to be investigated to which extent differences in endocranial morphology reflect differences in actual brain morphology and development, and to which extent they reflect different interactions of the brain and its case with the cranial base and face. Here we address this question by analyzing the effects of cranial integration on endocranial morphology. We test the 'spatial packing' and 'facial orientation' hypotheses, which propose that size and orientation of the neurocranium relative to the viscerocranium influence endocranial shape. Results show that a substantial proportion of endocranial shape variation along and across ontogenetic trajectories is due to cranial integration. Specifically, the uniquely globular shape of the human endocast mainly results from the combination of an exceptionally large brain with a comparatively small face. Overall, thus, cranial integration has pervasive effects on endocranial morphology, and only a comparatively small proportion of inter- and intra-taxon variation can directly be associated with variation in brain morphology.