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Alzheimer's disease (AD) and its associated pathology have been primarily identified in humans, who have relatively large brains and long lifespans. To expand what is known about aging and neurodegeneration across mammalian species, we characterized amyloid-beta (Aβ) and tau lesions in five species of aged felids (n = 9; cheetah, clouded leopard, African lion, serval, Siberian tiger). We performed immunohistochemistry to detect Aβ40 and Aβ42 in plaques and vessels and hyperphosphorylated tau in the temporal lobe gyrus sylvius and in the CA1 and CA3 subfields of the hippocampus. We also quantified the densities and morphological types of microglia expressing IBA1. We found that diffuse Aβ42 plaques, but not dense-core plaques, were present more frequently in the temporal cortex and tended to be more common than Aβ40 plaques across species. Conversely, vascular Aβ was labeled more consistently with Aβ40 for each species on average. Although all individuals showed some degree of Aβ40 and/or Aβ42 immunoreactivity, only the cheetahs and clouded leopards exhibited intraneuronal hyperphosphorylated tau (i.e., pretangles), which was more common in the hippocampus. Reactive, intermediate microglia were significantly associated with total Aβ40 vessel area and pretangle load in the hippocampus. This study demonstrates the co-occurrence of Aβ and tau pathology in two felid species, cheetahs and clouded leopards. Overall, these results provide an initial view of the manifestation of Aβ and tau pathology in aged, large-brained felids, which can be compared with markers of neurodegeneration across different taxa, including domestic cats, nonhuman primates, and humans., (© 2024 Wiley Periodicals LLC.)

Neuronal plasticity can vary remarkably in its form and degree across animal species. Adult neurogenesis, namely the capacity to produce new neurons from neural stem cells through adulthood, appears widespread in non-mammalian vertebrates, whereas it is reduced in mammals. A growing body of comparative studies also report variation in the occurrence and activity of neural stem cell niches between mammals, with a general trend of reduction from small-brained to large-brained species. Conversely, recent studies have shown that large-brained mammals host large amounts of neurons expressing typical markers of neurogenesis in the absence of cell division. In layer II of the cerebral cortex, populations of prenatally generated, non-dividing neurons continue to express molecules indicative of immaturity throughout life (cortical immature neurons; cINs). After remaining in a dormant state for a very long time, these cINs retain the potential of differentiating into mature neurons that integrate within the preexisting neural circuits. They are restricted to the paleocortex in small-brained rodents, while extending into the widely expanded neocortex of highly gyrencephalic, large-brained species. The current hypothesis is that these populations of non-newly generated "immature" neurons might represent a reservoir of developmentally plastic cells for mammalian species that are characterized by reduced stem cell-driven adult neurogenesis. This indicates that there may be a trade-off between various forms of plasticity that coexist during brain evolution. This balance may be necessary to maintain a "reservoir of plasticity" in brain regions that have distinct roles in species-specific socioecological adaptations, such as the neocortex and olfactory structures., (© 2023. The Author(s).)

Investigating evolutionary changes in frontal cortex microstructure is crucial to understanding how modifications of neuron and axon distributions contribute to phylogenetic variation in cognition. In the present study, we characterized microstructural components of dorsolateral prefrontal cortex, orbitofrontal cortex, and primary motor cortex from 14 primate species using measurements of neuropil fraction and immunohistochemical markers for fast-spiking inhibitory interneurons, large pyramidal projection neuron subtypes, serotonergic innervation, and dopaminergic innervation. Results revealed that the rate of evolutionary change was similar across these microstructural variables, except for neuropil fraction, which evolves more slowly and displays the strongest correlation with brain size. We also found that neuropil fraction in orbitofrontal cortex layers V-VI was associated with cross-species variation in performance on experimental tasks that measure self-control. These findings provide insight into the evolutionary reorganization of the primate frontal cortex in relation to brain size scaling and its association with cognitive processes., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The cerebral cortex accounts for substantial energy expenditure, primarily driven by the metabolic demands of synaptic signaling. Mitochondria, the organelles responsible for generating cellular energy, play a crucial role in this process. We investigated ultrastructural characteristics of the primary visual cortex in 18 phylogenetically diverse mammals, spanning a broad range of brain sizes from mouse to elephant. Our findings reveal remarkable uniformity in synapse density, postsynaptic density (PSD) length, and mitochondria density, indicating functional and metabolic constraints that maintain these fundamental features. Notably, we observed an average of 1.9 mitochondria per synapse across mammalian species. When considered together with the trend of decreasing neuron density with larger brain size, we find that brain enlargement in mammals is characterized by increasing proportions of synapses and mitochondria per cortical neuron. These results shed light on the adaptive mechanisms and metabolic dynamics that govern cortical ultrastructure across mammals., (© 2024 Wiley Periodicals LLC.)

Aging is associated with progressive gray matter loss in the brain. This spatially specific, morphological change over the life span in humans is also found in chimpanzees, and the comparison between these great ape species provides a unique evolutionary perspective on human brain aging. Here, we present a data-driven, comparative framework to explore the relationship between gray matter atrophy with age and recent cerebral expansion in the phylogeny of chimpanzees and humans. In humans, we show a positive relationship between cerebral aging and cortical expansion, whereas no such relationship was found in chimpanzees. This human-specific association between strong aging effects and large relative cortical expansion is particularly present in higher-order cognitive regions of the ventral prefrontal cortex and supports the "last-in-first-out" hypothesis for brain maturation in recent evolutionary development of human faculties.

Vision in humans and other primates enlists parallel processing streams in the dorsal and ventral visual cortex, known to support spatial and object processing, respectively. These streams are bridged, however, by a prominent white matter tract, the vertical occipital fasciculus (VOF), identified in both classical neuroanatomy and recent diffusion-weighted magnetic resonance imaging (dMRI) studies. Understanding the evolution of the VOF may shed light on its origin, function, and role in visually guided behaviors. To this end, we acquired high-resolution dMRI data from the brains of select mammalian species, including anthropoid and strepsirrhine primates, a tree shrew, rodents, and carnivores. In each species, we attempted to delineate the VOF after first locating the optic radiations in the occipital white matter. In all primate species examined, the optic radiation was flanked laterally by a prominent and coherent white matter fasciculus recognizable as the VOF. By contrast, the equivalent analysis applied to four non-primate species from the same superorder as primates (tree shrew, ground squirrel, paca, and rat) failed to reveal white matter tracts in the equivalent location. Clear evidence for a VOF was also absent in two larger carnivore species (ferret and fox). Although we cannot rule out the existence of minor or differently organized homologous fiber pathways in the non-primate species, the results suggest that the VOF has greatly expanded, or possibly emerged, in the primate lineage. This adaptation likely facilitated the evolution of unique visually guided behaviors in primates, with direct impacts on manual object manipulation, social interactions, and arboreal locomotion., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Humans exhibit sex differences in the prevalence of many neurodevelopmental disorders and neurodegenerative diseases. Here, we generated one of the largest multi-brain-region bulk transcriptional datasets for the rhesus macaque and characterized sex-biased gene expression patterns to investigate the translatability of this species for sex-biased neurological conditions. We identify patterns similar to those in humans, which are associated with overlapping regulatory mechanisms, biological processes, and genes implicated in sex-biased human disorders, including autism. We also show that sex-biased genes exhibit greater genetic variance for expression and more tissue-specific expression patterns, which may facilitate rapid evolution of sex-biased genes. Our findings provide insights into the biological mechanisms underlying sex-biased disease and support the rhesus macaque model for the translational study of these conditions., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Chimpanzees ( Pan troglodytes ) are humans' closest living relatives, making them the most directly relevant comparison point for understanding human brain evolution. Zeroing in on the differences in brain connectivity between humans and chimpanzees can provide key insights into the specific evolutionary changes that might have occured along the human lineage. However, conducting comparisons of brain connectivity between humans and chimpanzees remains challenging, as cross-species brain atlases established within the same framework are currently lacking. Without the availability of cross-species brain atlases, the region-wise connectivity patterns between humans and chimpanzees cannot be directly compared. To address this gap, we built the first Chimpanzee Brainnetome Atlas (ChimpBNA) by following a well-established connectivity-based parcellation framework. Leveraging this new resource, we found substantial divergence in connectivity patterns across most association cortices, notably in the lateral temporal and dorsolateral prefrontal cortex between the two species. Intriguingly, these patterns significantly deviate from the patterns of cortical expansion observed in humans compared to chimpanzees. Additionally, we identified regions displaying connectional asymmetries that differed between species, likely resulting from evolutionary divergence. Genes associated with these divergent connectivities were found to be enriched in cell types crucial for cortical projection circuits and synapse formation. These genes exhibited more pronounced differences in expression patterns in regions with higher connectivity divergence, suggesting a potential foundation for brain connectivity evolution. Therefore, our study not only provides a fine-scale brain atlas of chimpanzees but also highlights the connectivity divergence between humans and chimpanzees in a more rigorous and comparative manner and suggests potential genetic correlates for the observed divergence in brain connectivity patterns between the two species. This can help us better understand the origins and development of uniquely human cognitive capabilities.

The central sulcus divides the primary motor and somatosensory cortices in many anthropoid primate brains. Differences exist in the surface area and depth of the central sulcus along the dorso-ventral plane in great apes and humans compared to other primate species. Within hominid species, there are variations in the depth and aspect of their hand motor area, or knob, within the precentral gyrus. In this study, we used post-image analyses on magnetic resonance images to characterize the central sulcus shape of humans, chimpanzees (Pan troglodytes), gorillas (Gorilla gorilla), and orangutans (Pongo pygmaeus and Pongo abelii). Using these data, we examined the morphological variability of central sulcus in hominids, focusing on the hand region, a significant change in human evolution. We show that the central sulcus shape differs between great ape species, but all show similar variations in the location of their hand knob. However, the prevalence of the knob location along the dorso-ventral plane and lateralization differs between species and the presence of a second ventral motor knob seems to be unique to humans. Humans and orangutans exhibit the most similar and complex central sulcus shapes. However, their similarities may reflect divergent evolutionary processes related to selection for different positional and habitual locomotor functions., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The evolutionary history of canids and felids is marked by a deep time separation that has uniquely shaped their behavior and phenotype toward refined predatory abilities. The caudate nucleus is a subcortical brain structure associated with both motor control and cognitive, emotional, and executive functions. We used a combination of three-dimensional imaging, allometric scaling, and structural analyses to compare the size and shape characteristics of the caudate nucleus. The sample consisted of MRI scan data obtained from six canid species (Canis lupus lupus, Canis latrans, Chrysocyon brachyurus, Lycaon pictus, Vulpes vulpes, Vulpes zerda), two canid subspecies (Canis lupus familiaris, Canis lupus dingo), as well as three felids (Panthera tigris, Panthera uncia, Felis silvestris catus). Results revealed marked conservation in the scaling and shape attributes of the caudate nucleus across species, with only slight deviations. We hypothesize that observed differences in caudate nucleus size and structure for the domestic canids are reflective of enhanced cognitive and emotional pathways that possibly emerged during domestication., (© 2024 Wiley Periodicals LLC.)

Like the cerebralcortex, the surface of the cerebellum is repeatedly folded. Unlike the cerebralcortex, however, cerebellar folds are much thinner and more numerous; repeatthemselves largely along a single direction, forming accordion-like folds transverseto the mid-sagittal plane; and occur in all but the smallest cerebella. We haveshown previously that while the location of folds in mammalian cerebral cortex isclade-specific, the overall degree of folding strictly follows a universalpower law relating cortical thickness and the exposed and total surface areas predictedfrom the minimization of the effective free energy of an expanding, self-avoidingsurface of a certain thickness. Here we show that this scaling law extends tothe folding of the mid-sagittal sections of the cerebellum of 53 speciesbelonging to six mammalian clades. Simultaneously, we show that each clade hasa previously unsuspected distinctive spatial pattern of folding evident at themid-sagittal surface of the cerebellum. We note, however, that the mammaliancerebellum folds as a multi-fractal object, because of the difference betweenthe outside-in development of the cerebellar cortex around a preexisting coreof already connected white matter, compared to the inside-out development ofthe cerebral cortex with a white matter volume that develops as the cerebralcortex itself gains neurons. We conclude that repeated folding, one of the mostrecognizable features of biology, can arise simply from the interplay betweenthe universal applicability of the physics of self-organization and biological,phylogenetical clade-specific contingency, without the need for invokingselective pressures in evolution., (© 2024 The Authors. The Journal of Comparative Neurology published by Wiley Periodicals LLC.)

Introduction: Auditory information is relayed from the cochlea via the eighth cranial nerve to the dorsal and ventral cochlear nuclei (DCN, VCN). The organization, neurochemistry and circuitry of the cochlear nuclei (CN) have been studied in many species. It is well-established that glycine is an inhibitory transmitter in the CN of rodents and cats, with glycinergic cells in the DCN and VCN. There are, however, major differences in the laminar and cellular organization of the DCN between humans (and other primates) and rodents and cats. We therefore asked whether there might also be differences in glycinergic neurotransmission in the CN., Methods: We studied brainstem sections from humans, chimpanzees, and cats. We used antibodies to glycine receptors (GLYR) to identify neurons receiving glycinergic input, and antibodies to the neuronal glycine transporter (GLYT2) to immunolabel glycinergic axons and terminals. We also examined archival sections immunostained for calretinin (CR) and nonphosphorylated neurofilament protein (NPNFP) to try to locate the octopus cell area (OCA), a region in the VCN that rodents has minimal glycinergic input., Results: In humans and chimpanzees we found widespread immunolabel for glycine receptors in DCN and in the posterior (PVCN) and anterior (AVCN) divisions of the VCN. We found a parallel distribution of GLYT2-immunolabeled fibers and puncta. The data also suggest that, as in rodents, a region containing octopus cells in cats, humans and chimpanzees has little glycinergic input., Discussion: Our results show that glycine is a major transmitter in the human and chimpanzee CN, despite the species differences in DCN organization. The sources of the glycinergic input to the CN in humans and chimpanzees are not known., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Baizer, Sherwood, Hof, Baker and Witelson.)

Primate evolution has led to a remarkable diversity of behavioral specializations and pronounced brain size variation among species (Barton, 2012; DeCasien and Higham, 2019; Powell et al., 2017). Gene expression provides a promising opportunity for studying the molecular basis of brain evolution, but it has been explored in very few primate species to date (e.g. Khaitovich et al., 2005; Khrameeva et al., 2020; Ma et al., 2022; Somel et al., 2009). To understand the landscape of gene expression evolution across the primate lineage, we generated and analyzed RNA-seq data from four brain regions in an unprecedented eighteen species. Here, we show a remarkable level of variation in gene expression among hominid species, including humans and chimpanzees, despite their relatively recent divergence time from other primates. We found that individual genes display a wide range of expression dynamics across evolutionary time reflective of the diverse selection pressures acting on genes within primate brain tissue. Using our samples that represent a 190-fold difference in primate brain size, we identified genes with variation in expression most correlated with brain size. Our study extensively broadens the phylogenetic context of what is known about the molecular evolution of the brain across primates and identifies novel candidate genes for the study of genetic regulation of brain evolution., Competing Interests: KR, TZ, JP, EM, JE, MR, WH, PH, CS, AB, CB No competing interests declared, (© 2024, Rickelton et al.)

Introduction: Felids have evolved a specialized suite of morphological adaptations for obligate carnivory. Although the musculoskeletal anatomy of the Felidae has been studied extensively, the comparative neuroanatomy of felids is relatively unexplored. Little is known about how variation in the cerebral anatomy of felids relates to species-specific differences in sociality, hunting strategy, or activity patterns., Methods: We quantitatively analyzed neuropil variation in the prefrontal, primary motor, and primary visual cortices of six species of Felidae (Panthera leo, Panthera uncia, Panthera tigris, Panthera leopardus, Acinonyx jubatus, Felis sylvestris domesticus) to investigate relationships with brain size, neuronal cell parameters, and select behavioral and ecological factors. Neuropil is the dense, intricate network of axons, dendrites, and synapses in the brain, playing a critical role in information processing and communication between neurons., Results: There were significant species and regional differences in neuropil proportions, with African lion, cheetah, and tiger having more neuropil in all three cortical regions in comparison to the other species. Based on regression analyses, we find that the increased neuropil fraction in the prefrontal cortex supports social and behavioral flexibility, while in the primary motor cortex, this facilitates the neural activity needed for hunting movements. Greater neuropil fraction in the primary visual cortex may contribute to visual requirements associated with diel activity patterns., Conclusion: These results provide a cross-species comparison of neuropil fraction variation in the Felidae, particularly the understudied Panthera, and provide evidence for convergence of the neuroanatomy of Panthera and cheetahs., (© 2024 S. Karger AG, Basel.)

Human newborns are considered altricial compared with other primates because they are relatively underdeveloped at birth. However, in a broader comparative context, other mammals are more altricial than humans. It has been proposed that altricial development evolved secondarily in humans due to obstetrical or metabolic constraints, and in association with increased brain plasticity. To explore this association, we used comparative data from 140 placental mammals to measure how altriciality evolved in humans and other species. We also estimated how changes in brain size and gestation length influenced the timing of neurodevelopment during hominin evolution. Based on our data, humans show the highest evolutionary rate to become more altricial (measured as the proportion of adult brain size at birth) across all placental mammals, but this results primarily from the pronounced postnatal enlargement of brain size rather than neonatal changes. In addition, we show that only a small number of neurodevelopmental events were shifted to the postnatal period during hominin evolution, and that they were primarily related to the myelination of certain brain pathways. These results indicate that the perception of human altriciality is mostly driven by postnatal changes, and they point to a possible association between the timing of myelination and human neuroplasticity., (© 2023. The Author(s).)

Comparative "omics" studies have revealed unique aspects of human neurobiology, yet an evolutionary perspective of the brain N-glycome is lacking. We performed multiregional characterization of rat, macaque, chimpanzee, and human brain N-glycomes using chromatography and mass spectrometry and then integrated these data with complementary glycotranscriptomic data. We found that, in primates, the brain N-glycome has diverged more rapidly than the underlying transcriptomic framework, providing a means for rapidly generating additional interspecies diversity. Our data suggest that brain N-glycome evolution in hominids has been characterized by an overall increase in complexity coupled with a shift toward increased usage of α(2-6)-linked N -acetylneuraminic acid. Moreover, interspecies differences in the cell type expression pattern of key glycogenes were identified, including some human-specific differences, which may underpin this evolutionary divergence. Last, by comparing the prenatal and adult human brain N-glycomes, we uncovered region-specific neurodevelopmental pathways that lead to distinct spatial N-glycosylation profiles in the mature brain.

The cognitive abilities of humans are distinctive among primates, but their molecular and cellular substrates are poorly understood. We used comparative single-nucleus transcriptomics to analyze samples of the middle temporal gyrus (MTG) from adult humans, chimpanzees, gorillas, rhesus macaques, and common marmosets to understand human-specific features of the neocortex. Human, chimpanzee, and gorilla MTG showed highly similar cell-type composition and laminar organization as well as a large shift in proportions of deep-layer intratelencephalic-projecting neurons compared with macaque and marmoset MTG. Microglia, astrocytes, and oligodendrocytes had more-divergent expression across species compared with neurons or oligodendrocyte precursor cells, and neuronal expression diverged more rapidly on the human lineage. Only a few hundred genes showed human-specific patterning, suggesting that relatively few cellular and molecular changes distinctively define adult human cortical structure.

The nucleus accumbens (NAc) is central to motivation and action, exhibiting one of the highest densities of neuropeptide Y (NPY) in the brain. Within the NAc, NPY plays a role in reward and is involved in emotional behavior and in increasing alcohol and drug addiction and fat intake. Here, we examined NPY innervation and neurons of the NAc in humans and other anthropoid primates in order to determine whether there are differences among these various species that would correspond to behavioral or life history variables. We quantified NPY-immunoreactive axons and neurons in the NAc of 13 primate species, including humans, great apes, and monkeys. Our data show that the human brain is unique among primates in having denser NPY innervation within the NAc, as measured by axon length density to neuron density, even after accounting for brain size. Combined with our previous finding of increased dopaminergic innervation in the same region, our results suggest that the neurochemical profile of the human NAc appears to have rendered our species uniquely susceptible to neurophysiological conditions such as addiction. The increase in NPY specific to the NAc may represent an adaptation that favors fat intake and contributes to an increased vulnerability to eating disorders, obesity, as well as alcohol and drug dependence. Along with our findings for dopamine, these deeply rooted structural attributes of the human brain are likely to have emerged early in the human clade, laying the groundwork for later brain expansion and the development of cognitive and behavioral specializations.

Human language is supported by a cortical network involving Broca's area, which comprises Brodmann Areas 44 and 45 (BA44 and BA45). While cytoarchitectonic homolog areas have been identified in nonhuman primates, it remains unknown how these regions evolved to support human language. Here, we use histological data and advanced cortical registration methods to precisely compare the morphology of BA44 and BA45 in humans and chimpanzees. We found a general expansion of Broca's areas in humans, with the left BA44 enlarging the most, growing anteriorly into a region known to process syntax. Together with recent functional and receptorarchitectural studies, our findings support the conclusion that BA44 evolved from an action-related region to a bipartite system, with a posterior portion supporting action and an anterior portion supporting syntactic processes. Our findings add novel insights to the longstanding debate on the relationship between language and action, and the evolution of Broca's area., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Gallardo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Human-specific genomic changes contribute to the unique functionalities of the human brain 1-5 . The cellular heterogeneity of the human brain 6,7 and the complex regulation of gene expression highlight the need to characterize human-specific molecular features at cellular resolution. Here we analysed single-nucleus RNA-sequencing and single-nucleus assay for transposase-accessible chromatin with sequencing datasets for human, chimpanzee and rhesus macaque brain tissue from posterior cingulate cortex. We show a human-specific increase of oligodendrocyte progenitor cells and a decrease of mature oligodendrocytes across cortical tissues. Human-specific regulatory changes were accelerated in oligodendrocyte progenitor cells, and we highlight key biological pathways that may be associated with the proportional changes. We also identify human-specific regulatory changes in neuronal subtypes, which reveal human-specific upregulation of FOXP2 in only two of the neuronal subtypes. We additionally identify hundreds of new human accelerated genomic regions associated with human-specific chromatin accessibility changes. Our data also reveal that FOS::JUN and FOX motifs are enriched in the human-specifically accessible chromatin regions of excitatory neuronal subtypes. Together, our results reveal several new mechanisms underlying the evolutionary innovation of human brain at cell-type resolution., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Identifying the evolutionary origins of human speech remains a topic of intense scientific interest. Here we describe a unique feature of adult human neuroanatomy compared to chimpanzees and other primates that may provide an explanation of changes that occurred to enable the capacity for speech. That feature is the Prefrontal extent of the Frontal Operculum (PFOp) region, which is located in the ventrolateral prefrontal cortex, adjacent and ventromedial to the classical Broca's area. We also show that, in chimpanzees, individuals with the most human-like PFOp, particularly in the left hemisphere, have greater oro-facial and vocal motor control abilities. This critical discovery, when combined with recent paleontological evidence, suggests that the PFOp is a recently evolved feature of human cortical structure (perhaps limited to the genus Homo) that emerged in response to increasing selection for cognitive and motor functions evident in modern speech abilities., (© 2023. The Author(s).)

Fossil endocasts record features of brains from the past: size, shape, vasculature, and gyrification. These data, alongside experimental and comparative evidence, are needed to resolve questions about brain energetics, cognitive specializations, and developmental plasticity. Through the application of interdisciplinary techniques to the fossil record, paleoneurology has been leading major innovations. Neuroimaging is shedding light on fossil brain organization and behaviors. Inferences about the development and physiology of the brains of extinct species can be experimentally investigated through brain organoids and transgenic models based on ancient DNA. Phylogenetic comparative methods integrate data across species and associate genotypes to phenotypes, and brains to behaviors. Meanwhile, fossil and archeological discoveries continuously contribute new knowledge. Through cooperation, the scientific community can accelerate knowledge acquisition. Sharing digitized museum collections improves the availability of rare fossils and artifacts. Comparative neuroanatomical data are available through online databases, along with tools for their measurement and analysis. In the context of these advances, the paleoneurological record provides ample opportunity for future research. Biomedical and ecological sciences can benefit from paleoneurology's approach to understanding the mind as well as its novel research pipelines that establish connections between neuroanatomy, genes and behavior., (© 2023. The Author(s).)

Aging and neurodegenerative disorders, such as Alzheimer's disease (AD), trigger an immune response known as glial activation in the brain. Recent evidence indicates species differences in inflammatory responses to AD pathology, highlighting the need for additional comparative studies to further understand human-specific neuropathologies. In the present study, we report on the occurrence of astrogliosis, microglial activation, and their relationship with age and AD-like pathology in a cohort of male and female chimpanzees (Pan troglodytes). Chimpanzees with severe astrogliosis exhibited widespread upregulation of hypertrophic astrocytes immunoreactive for glial fibrillary acidic protein (GFAP) throughout all layers of the dorsolateral prefrontal cortex and a loss of the interlaminar palisade. In addition, extreme astrogliosis was associated with increased astrocyte density in the absence of significant microglial activation and AD lesions. A shift from decreased resting to increased phagocytotic microglia occurred with aging, although proliferation was absent and no changes in astrogliosis was observed. Vascular amyloid correlated with decreased astrocyte and microglia densities, while tau lesions were associated with morphological changes in microglia and greater total glia density and glia: neuron ratio. These results further our understanding of inflammatory processes within the chimpanzee brain and provide comparative data to improve our understanding of human aging and neuropathological processes., (© 2023 The Authors. Journal of Neuroscience Research published by Wiley Periodicals LLC.)

Humans and chimpanzees are genetically similar and share a number of life history, behavioral, cognitive and neuroanatomical similarities. Notwithstanding, our understanding of age-related changes in cognitive and motor functions in chimpanzees remains largely unstudied despite recent evident demonstrating that chimpanzees exhibit many of the same neuropathological features of Alzheimer's disease observed in human postmortem brains. Here, we examined age-related differences in cognition and cortical thickness measured from magnetic resonance images in a sample of 215 chimpanzees ranging in age between 9 and 54 years. We found that chimpanzees showed global and region-specific thinning of cortex with increasing age. Further, within the elderly cohort, chimpanzees that performed better than average had thicker cortex in frontal, temporal and parietal regions compared to chimpanzees that performed worse than average. Independent of age, we also found sex differences in cortical thickness in 4 brain regions. Males had higher adjusted cortical thickness scores for the caudal anterior cingulate, rostral anterior cingulate, and medial orbital frontal while females had higher values for the inferior parietal cortex. We found no evidence that increasing age nor sex was associated with asymmetries in cortical thickness. Moreover, age-related differences in cognitive function were only weakly associated with asymmetries in cortical thickness. In summary, as has been reported in humans and other primates, elderly chimpanzees show thinner cortex and variation in cortical thickness is associated with general cognitive functions., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Joint attention (JA) is an important milestone in human infant development and is predictive of the onset of language later in life. Clinically, it has been reported that children at risk for or with a diagnosis of autism spectrum disorder (ASD) perform more poorly on measures of JA compared to neurotypical controls. JA is not unique to humans but has also been reported in great apes and to a lesser extent in more distantly related monkeys. Further, individual differences in JA among chimpanzees are associated with polymorphisms in the vasopressin and oxytocin genes, AVPR1A and OXTR. Here, we tested whether individual variation in DNA methylation of OXTR and AVPR1A were associated with performance on JA tasks in chimpanzees. We found that individual differences in JA performance was associated with AVPR1A methylation, but not OXTR methylation in the chimpanzees. The collective results provide further evidence of the role of AVPR1A in JA abilities in chimpanzees. The results further suggest that methylation values for AVPR1A may be useful biomarkers for identifying individuals at risk for ASD or related neurodevelopmental disorders associated with impairments in JA abilities., (© 2023 International Society for Autism Research and Wiley Periodicals LLC.)

The superior olivary complex (SOC) is a collection of nuclei in the hindbrain of mammals with numerous roles in hearing, including localization of sound sources in the environment, encoding temporal and spectral elements of sound, and descending modulation of the cochlea. While there have been several investigations of the SOC in primates, there are discrepancies in the descriptions of nuclear borders and even the presence of certain cell groups among studies and species. Herein, we aimed to clarify some of these issues by characterizing the SOC from chimpanzees using Nissl staining, quantitative morphometry and immunohistochemistry. We found the medial superior olive (MSO) to be the largest of the SOC nuclei and the arrangement of its neurons and peri-MSO to be very similar to humans. Additionally, we found neurons in the medial nucleus of the trapezoid body (MNTB) to be immunopositive for the calcium binding protein calbindin. Further, most neurons in the MNTB, and some neurons in the lateral nucleus of the trapezoid body were associated with large, calretinin-immunoreactive calyx terminals. Together, these findings indicate the organization of the SOC of chimpanzees is organized very similar to the SOC in humans and suggests modifications to this region among species consistent with differences in head/body size, restricted hearing range and sensitivity to low frequency sounds., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The superior temporal sulcus (STS) is a conserved fold that divides the middle and superior temporal gyri. In humans, there is considerable variation in the shape, folding pattern, lateralization, and depth of the STS that have been reported to be associated with social cognition and linguistic functions. We examined the role that genetic factors play on individual variation in STS morphology in chimpanzees. The surface area and depth of the STS were quantified in sample of 292 captive chimpanzees comprised of two genetically isolated population of individuals. The chimpanzees had been previously genotyped for AVPR1A and KIAA0319, two genes that play a role in social cognition and communication in humans. Single nucleotide polymorphisms in the KIAA0319 and AVPR1A genes were associated with average depth as well as asymmetries in the STS. By contrast, we found no significant effects of these KIA0319 and AVPR1A polymorphism on surface area and depth measures for the central sulcus. The overall findings indicate that genetic factors account for a small to moderate amount of variation in STS morphology in chimpanzees. These findings are discussed in the context of the role of the STS in social cognition and language in humans and their potential evolutionary origins., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The parietal lobe is a region of especially pronounced change in human brain evolution. Based on comparative neuroanatomical studies, the inferior parietal lobe (IPL) has been shown to be disproportionately larger in humans relative to chimpanzees and macaques. However, it remains unclear whether the underlying histological architecture of IPL cortical areas displays human-specific organization. Chimpanzees are among the closest living relatives of humans, making them an ideal comparative species to investigate potential evolutionary changes in the IPL. We parcellated the chimpanzee IPL using cytoarchitecture and myeloarchitecture, in combination with quantitative comparison of cellular features between the identified cortical areas. Four major areas on the lateral convexity of the chimpanzee IPL (PF, PFG, PG, OPT) and two opercular areas (PFOP, PGOP) were identified, similar to what has been observed in macaques. Analysis of the quantitative profiles of cytoarchitecture showed that cell profile density was significantly different in a combination of layers III, IV, and V between bordering cortical areas, and that the density profiles of these six areas supports their classification as distinct. The similarity to macaque IPL cytoarchitecture suggests that chimpanzees share homologous IPL areas. In comparison, human rostral IPL is reported to differ in its anatomical organization and to contain additional subdivisions, such as areas PFt and PFm. These changes in human brain evolution might have been important as tool making capacities became more complex., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Language and complex tool use are often cited as behaviors unique to humans and may be evolutionarily linked owing to the underlying cognitive processes they have in common. We executed a quantitative activation likelihood estimation (ALE) meta-analysis (GingerALE 2.3) on published, whole-brain neuroimaging studies to identify areas associated with syntactic processing and/or tool use in humans. Significant clusters related to syntactic processing were identified in areas known to be related to language production and comprehension, including bilateral Broca's area in the inferior frontal gyrus. Tool use activation clusters were all in the left hemisphere and included the primary motor cortex and premotor cortex, in addition to other areas involved with sensorimotor transformation. Activation shared by syntactic processing and tool use was only significant at one cluster, located in the pars opercularis of the left inferior frontal gyrus. This minimal overlap between syntactic processing and tool use activation from our meta-analysis of neuroimaging studies indicates that there is not a widespread common neural network between the two. Broca's area may serve as an important hub that was initially recruited in early human evolution in the context of simple tool use, but was eventually co-opted for linguistic purposes, including the sequential and hierarchical ordering processes that characterize syntax. In the future, meta-analyses of additional components of language may allow for a more comprehensive examination of the functional networks that underlie the coevolution of human language and complex tool use., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Astrocytes are the main homeostatic cell of the brain involved in many processes related to cognition, immune response, and energy expenditure. It has been suggested that the distribution of astrocytes is associated with brain size, and that they are specialized in humans. To evaluate these, we quantified astrocyte density, soma volume, and total glia density in layer I and white matter in Brodmann's area 9 of humans, chimpanzees, baboons, and macaques. We found that layer I astrocyte density, soma volume, and ratio of astrocytes to total glia cells were highest in humans and increased with brain size. Overall glia density in layer I and white matter were relatively invariant across brain sizes, potentially due to their important metabolic functions on a per volume basis. We also quantified two transporters involved in metabolism through the astrocyte-neuron lactate shuttle, excitatory amino acid transporter 2 (EAAT2) and glucose transporter 1 (GLUT1). We expected these transporters would be increased in human brains due to their high rate of metabolic consumption and associated gene activity. While humans have higher EAAT2 cell density, GLUT1 vessel volume, and GLUT1 area fraction compared to baboons and chimpanzees, they did not differ from macaques. Therefore, EAAT2 and GLUT1 are not related to increased energetic demands of the human brain. Taken together, these data provide evidence that astrocytes play a unique role in both brain expansion and evolution among primates, with an emphasis on layer I astrocytes having a potentially significant role in human-specific metabolic processing and cognition., (© 2022 Wiley Periodicals LLC.)

Chimpanzees have consistent individual differences in behaviour, also referred to as personality. Similar to human personality structure, five dimensions are commonly found in chimpanzee studies that show evidence for convergent and predictive validity (Dominance, Openness, Extraversion, Agreeableness, and Reactivity/Undependability). These dimensions are to some extent heritable, indicating a genetic component that explains part of the variation in personality scores, but are also influenced by environmental factors, such as the early social rearing background of the individuals. In this study, we investigated the role of epigenetic modification of the dopamine receptor D2 gene ( DRD2 ) as a potential mechanism underlying personality variation in 51 captive chimpanzees. We used previously collected personality trait rating data and determined levels of DRD2 CpG methylation in peripheral blood samples for these same individuals. Results showed that DRD2 methylation is most strongly associated with Extraversion, and that varying methylation levels at specific DRD2 sites are associated with changes in Extraversion in nursery-reared, but not mother-reared, individuals. These results highlight the role of dopaminergic signalling in chimpanzee personality, and indicate that environmental factors, such as social experiences early in life, can have long-lasting behavioural effects, potentially through modification of the epigenome. These findings add to the growing evidence demonstrating the importance of the experience-dependent methylome for the development of complex social traits like personality.

Epigenetic age has emerged as an important biomarker of biological ageing. It has revealed that some tissues age faster than others, which is vital to understanding the complex phenomenon of ageing and developing effective interventions. Previous studies have demonstrated that humans exhibit heterogeneity in pace of epigenetic ageing among brain structures that are consistent with differences in structural and microanatomical deterioration. Here, we add comparative data on epigenetic brain ageing for chimpanzees, humans' closest relatives. Such comparisons can further our understanding of which aspects of human ageing are evolutionarily conserved or specific to our species, especially given that humans are distinguished by a long lifespan, large brain, and, potentially, more severe neurodegeneration with age. Specifically, we investigated epigenetic ageing of the dorsolateral prefrontal cortex and cerebellum, of humans and chimpanzees by generating genome-wide CpG methylation data and applying established epigenetic clock algorithms to produce estimates of biological age for these tissues. We found that both species exhibit relatively slow epigenetic ageing in the brain relative to blood. Between brain structures, humans show a faster rate of epigenetic ageing in the dorsolateral prefrontal cortex compared to the cerebellum, which is consistent with previous findings. Chimpanzees, in contrast, show comparable rates of epigenetic ageing in the two brain structures. Greater epigenetic change in the human dorsolateral prefrontal cortex compared to the cerebellum may reflect both the protracted development of this structure in humans and its greater age-related vulnerability to neurodegenerative pathology.

While low serotonergic activity is often associated with psychological disorders such as depression, anxiety, mood, and personality disorders, variations in serotonin also contribute to normal personality differences. In this study, we investigated the role of blood DNA methylation levels at individual CpG sites of two key serotonergic genes (serotonin receptor gene 1A, HTR1A ; serotonin transporter gene, SLC6A4 ) in predicting the personalities of captive chimpanzees. We found associations between methylation at 9/48 CpG sites with four personality dimensions: Dominance, Reactivity/Dependability, Agreeableness, and Openness. Directionality of effects were CpG location-dependent and confirmed a role of serotonergic methylation in reducing anxiety (Dominance) and aggression-related personality (Reactivity/Undependability) while simultaneously promoting prosocial (Agreeableness) and exploratory personalities (Openness). Although early-life adversity has been shown to impact serotonergic methylation patterns in other species, here, atypical early social rearing experiences only had a modest impact on CpG methylation levels in this chimpanzee sample. The precise environmental factors impacting serotonergic methylation in chimpanzees remain to be identified. Nevertheless, our study suggests a role in shaping natural variation in animal personalities. The results of this study offer a basis for future hypothesis-driven testing in additional populations and species to better understand the impact of ecology and evolution on complex behavioral traits.

Background: Dehydroepiandrosterone-sulfate is the most abundant circulating androgen in humans and other catarrhines. It is involved in several biological functions, such as testosterone production, glucocorticoid antagonist actions, neurogenesis and neuroplasticty. Although the role of dehydroepiandrosterone-sulfate (DHEAS) in cognition remains elusive, the DHEAS/cortisol ratio has been positively associated with a slower cognitive age-decline and improved mood in humans. Whether this relationship is found in nonhuman primates remains unknown., Methods: We measured DHEAS and cortisol levels in serum of 107 adult chimpanzees to investigate the relationship between DHEAS levels and age. A subset of 21 chimpanzees was used to test the potential associations between DHEAS, cortisol, and DHEAS/cortisol ratio in cognitive function, taking into account age, sex, and their interactions. We tested for cognitive function using the primate cognitive test battery (PCTB) and principal component analyses to categorize cognition into three components: spatial relationship tasks, tool use and social communication tasks, and auditory-visual sensory perception tasks., Results: DHEAS levels, but not the DHEAS/cortisol ratio, declined with age in chimpanzees. Our analyses for spatial relationships tasks revealed a significant, positive correlation with the DHEAS/cortisol ratio. Tool use and social communication had a negative relationship with age. Our data show that the DHEAS/cortisol ratio, but not DHEAS individually, is a promising predictor of spatial cognition in chimpanzees., Competing Interests: The authors declare there are no competing interests., (©2022 Takeshita et al.)

The granular dorsolateral prefrontal cortex (dlPFC) is an evolutionary specialization of primates that is centrally involved in cognition. We assessed more than 600,000 single-nucleus transcriptomes from adult human, chimpanzee, macaque, and marmoset dlPFC. Although most cell subtypes defined transcriptomically are conserved, we detected several that exist only in a subset of species as well as substantial species-specific molecular differences across homologous neuronal, glial, and non-neural subtypes. The latter are exemplified by human-specific switching between expression of the neuropeptide somatostatin and tyrosine hydroxylase, the rate-limiting enzyme in dopamine production in certain interneurons. The above molecular differences are also illustrated by expression of the neuropsychiatric risk gene FOXP2 , which is human-specific in microglia and primate-specific in layer 4 granular neurons. We generated a comprehensive survey of the dlPFC cellular repertoire and its shared and divergent features in anthropoid primates.

Humans and chimpanzees both exhibit a diverse set of tool use skills which suggests selection for tool manufacture and use occurred in the common ancestors of the two species. Our group has previously reported phenotypic and genetic associations between tool use skill and gray matter covariation, as quantified by source-based morphometry (SBM), in chimpanzees. As a follow up study, here we evaluated repeatability in heritability in SBM components and their phenotypic association with tool use skill in two genetically independent chimpanzee cohorts. Within the two independent cohorts of chimpanzees, we identified 8 and 16 SBM components, respectively. Significant heritability was evident for multiple SBM components within both cohorts. Further, phenotypic associations between tool use performance and the SBM components were largely consistent between the two cohorts; the most consistent finding being an association between tool use performance and an SBM component including the posterior superior temporal sulcus (STS) and superior temporal gyrus (STG), and the interior and superior parietal regions (p < 0.05). These findings indicate that the STS, STG, and parietal cortices are phenotypically and genetically implicated in chimpanzee tool use abilities., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Using choline acetyltransferase immunohistochemistry, we describe the nuclear parcellation of the cholinergic system in the brains of two apes, a lar gibbon (Hylobates lar) and a chimpanzee (Pan troglodytes). The cholinergic nuclei observed in both apes studied are virtually identical to that observed in humans and show very strong similarity to the cholinergic nuclei observed in other primates and mammals more generally. One specific difference between humans and the two apes studied is that, with the specific choline acetyltransferase antibody used, the cholinergic pyramidal neurons observed in human cerebral cortex were not labeled. When comparing the two apes studied and humans to other primates, the presence of a greatly expanded cholinergic medullary tegmental field, and the presence of cholinergic neurons in the intermediate and dorsal horns of the cervical spinal cord are notable variations of the distribution of cholinergic neurons in apes compared to other primates. These neurons may play an important role in the modulation of ascending and descending neural transmissions through the spinal cord and caudal medulla, potentially related to the differing modes of locomotion in apes compared to other primates. Our observations also indicate that the average soma volume of the neurons forming the laterodorsal tegmental nucleus (LDT) is larger than those of the pedunculopontine nucleus (PPT) in both the lar gibbon and chimpanzee. This variability in soma volume appears to be related to the size of the adult derivatives of the alar and basal plate across mammalian species., (© 2021 American Association for Anatomy.)

Using tyrosine hydroxylase immunohistochemistry, we describe the nuclear parcellation of the catecholaminergic system in the brains of a lar gibbon (Hylobates lar) and a chimpanzee (Pan troglodytes). The parcellation of catecholaminergic nuclei in the brains of both apes is virtually identical to that observed in humans and shows very strong similarities to that observed in mammals more generally, particularly other primates. Specific variations of this system in the apes studied include an unusual high-density cluster of A10dc neurons, an enlarged retrorubral nucleus (A8), and an expanded distribution of the neurons forming the dorsolateral division of the locus coeruleus (A4). The additional A10dc neurons may improve dopaminergic modulation of the extended amygdala, the enlarged A8 nucleus may be related to the increased use of communicative facial expressions in the hominoids compared to other primates, while the expansion of the A4 nucleus appears to be related to accelerated evolution of the cerebellum in the hominoids compared to other primates. In addition, we report the presence of a compact division of the locus coeruleus proper (A6c), as seen in other primates, that is not present in other mammals apart from megachiropteran bats. The presence of this nucleus in primates and megachiropteran bats may reflect homology or homoplasy, depending on the evolutionary scenario adopted. The fact that the complement of homologous catecholaminergic nuclei is mostly consistent across mammals, including primates, is advantageous for the selection of model animals for the study of specific dysfunctions of the catecholaminergic system in humans., (© 2021 American Association for Anatomy.)

Employing orexin-A immunohistochemical staining we describe the nuclear parcellation of orexinergic neurons in the hypothalami of a lar gibbon and a chimpanzee. The clustering of orexinergic neurons within the hypothalamus and the terminal networks follow the patterns generally observed in other mammals, including laboratory rodents, strepsirrhine primates and humans. The orexinergic neurons were found within three distinct clusters in the ape hypothalamus, which include the main cluster, zona incerta cluster and optic tract cluster. In addition, the orexinergic neurons of the optic tract cluster appear to extend to a more rostral and medial location than observed in other species, being observed in the tuberal region in the anterior ventromedial aspect of the hypothalamus. While orexinergic terminal networks were observed throughout the brain, high density terminal networks were observed within the hypothalamus, medial and intralaminar nuclei of the dorsal thalamus, and within the serotonergic and noradrenergic regions of the midbrain and pons, which is typical for mammals. The expanded distribution of orexinergic neurons into the tuberal region of the ape hypothalamus, is a feature that needs to be investigated in other primate species, but appears to correlate with orexin gene expression in the same region of the human hypothalamus, but these neurons are not revealed with immunohistochemical staining in humans. Thus, it appears that apes have a broader distribution of orexinergic neurons compared to other primate species, but that the neurons within this extension of the optic tract cluster in humans, while expressing the orexin gene, do not produce the neuropeptide., (© 2021 American Association for Anatomy.)

In the current study, we detail, through the analysis of immunohistochemically stained sections, the morphology and nuclear parcellation of the serotonergic neurons present in the brainstem of a lar gibbon and a chimpanzee. In general, the neuronal morphology and nuclear organization of the serotonergic system in the brains of these two species of apes follow that observed in a range of Eutherian mammals and are specifically very similar to that observed in other species of primates. In both of the apes studied, the serotonergic nuclei could be readily divided into two distinct groups, a rostral and a caudal cluster, which are found from the level of the decussation of the superior cerebellar peduncle to the spinomedullary junction. The rostral cluster is comprised of the caudal linear, supralemniscal, and median raphe nuclei, as well as the six divisions of the dorsal raphe nuclear complex. The caudal cluster contains several distinct nuclei and nuclear subdivisions, including the raphe magnus nucleus and associated rostral and caudal ventrolateral (CVL) serotonergic groups, the raphe pallidus, and raphe obscurus nuclei. The one deviation in organization observed in comparison to other primate species is an expansion of both the number and distribution of neurons belonging to the lateral division of the dorsal raphe nucleus in the chimpanzee. It is unclear whether this expansion occurs in humans, thus at present, this expansion sets the chimpanzee apart from other primates studied to date., (© 2021 American Association for Anatomy.)

The midsagittal area of the corpus callosum (CC) is frequently studied in relation to brain development, connectivity, and function. Here we quantify myelin characteristics from electron microscopy to understand more fully differential patterns of white matter development occurring within the CC. We subdivided midsagittal regions of the CC into: I-rostrum and genu, II-rostral body, III-anterior midbody, IV-posterior midbody, and V-isthmus and splenium. The sample represented capuchin monkeys ranging in age from 2 weeks to 35 years (Sapajus [Cebus] apella, n = 8). Measurements of myelin thickness, myelin fraction, and g-ratio were obtained in a systematic random fashion. We hypothesized there would be a period of rapid myelin growth within the CC in early development. Using a locally weighted regression analysis (LOESS), we found regional differences in myelin characteristics, with posterior regions showing more rapid increases in myelin thickness and sharper decreases in g-ratio in early development. The most anterior region showed the most sustained growth in myelin thickness. For all regions over the lifespan, myelin fraction increased, plateaued, and decreased. These results suggest differential patterns of nonlinear myelin growth occur early in development and well into adulthood in the CC of capuchin monkeys., (© 2022. The Author(s).)

The corpus callosum (CC) is the major white matter tract connecting the left and right cerebral hemispheres. It has been hypothesized that individual variation in CC morphology is negatively associated with forebrain volume (FBV) and this accounts for variation in behavioral and brain asymmetries as well as sex differences. To test this hypothesis, CC surface area and thickness as well as FBV was quantified in 221 chimpanzees with known pedigrees. CC surface area, thickness and FBV were significantly heritable and phenotypically associated with each other; however, no significant genetic association was found between FBV, CC surface area and thickness. The CC surface area and thickness measures were also found to be significantly heritable in both chimpanzee cohorts as were phenotypic associations with variation in asymmetries in tool use skill, suggesting that these findings are reproducible. Finally, significant phenotypic and genetic associations were found between hand use skill and region-specific variation in CC surface area and thickness. These findings suggest that common genes may underlie individual differences in chimpanzee tool use skill and interhemispheric connectivity as manifest by variation in surface area and thickness within the anterior region of the CC., (© 2021 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.)

Varicose projection astrocytes (VP-As) are found in the cerebral cortex and have been described to be specific to humans and chimpanzees. To further examine the phylogenetic distribution of this cell type, we analyzed cortical tissue from several primates ranging from primitive primates to primates evolutionary closer to human such as apes. We specifically analyzed tissue from four strepsirrhine species, one tarsier, six species of platyrrhine monkeys, ten species of cercopithecoid monkeys, two hylobatid ape species, four to six cases each of chimpanzee, bonobo, gorilla, and orangutan, and thirteen human. We found that VP-As were present only in human and other apes (hominoids) and were absent in all other species. We showed that VP-As are localized to layer VI and the superficial white matter of the cortex. The presence of VP-As co-occured with interlaminar astrocytes that also had varicosities in their processes. Due to their location, their long tangential processes, and their irregular presence within species, we propose that VP-As are astrocytes that develop varicosities under specific conditions and that are not a distinct astrocyte type., (© 2021 Wiley Periodicals LLC.)

Determining the impact that the KIAA0319 gene has on primate brain morphology can provide insight into the evolution of human cognition and language systems. Here, we tested whether polymorphisms in KIAA0319 in chimpanzees account for gray matter volumetric variation in brain regions implicated in language and communication (particularly within the posterior superior temporal gyrus and inferior frontal gyrus). First, we identified the nature and frequencies of single nucleotide variants (SNVs) in KIAA0319 in a sample of unrelated chimpanzees ( Pan troglodytes spp.). Next, we genotyped a subset of SNVs (those important for gene regulation or likely to alter protein structure/function) in a sample of chimpanzees for which in vivo T1-structural magnetic resonance imaging scans had been obtained. We then used source-based morphometry (SBM) to test for whole-brain gray matter covariation differences between chimpanzees with different KIAA0319 alleles. Finally, using histologic sections of 15 postmortem chimpanzee brains, we analyzed microstructural variation related to KIAA0319 polymorphisms in the posterior superior temporal cortex. We found that the SNVs were associated with variation in gray matter within several brain regions, including the posterior superior temporal gyrus (a region associated with language comprehension and production in humans). The microstructure analysis further revealed hemispheric differences in neuropil fraction, indicating that KIAA0319 expression may be involved in regulation of processes related to the formation and maintenance of synapses, dendrites, or axons within regions associated with communication., (Copyright © 2021 Hopkins et al.)

While humans exhibit a significant degree of neuropathological changes associated with deficits in cognitive and memory functions during aging, non-human primates (NHP) present with more variable expressions of pathological alterations among individuals and species. As such, NHP with long life expectancy in captivity offer an opportunity to study brain senescence in the absence of the typical cellular pathology caused by age-related neurodegenerative illnesses commonly seen in humans. Age-related changes at neuronal population, single cell, and synaptic levels have been well documented in macaques and marmosets, while age-related and Alzheimer's disease-like neuropathology has been characterized in additional species including lemurs as well as great apes. We present a comparative overview of existing neuropathologic observations across the primate order, including classic age-related changes such as cell loss, amyloid deposition, amyloid angiopathy, and tau accumulation. We also review existing cellular and ultrastructural data on neuronal changes, such as dendritic attrition and spine alterations, synaptic loss and pathology, and axonal and myelin pathology, and discuss their repercussions on cellular and systems function and cognition., (© 2021 Wiley Periodicals LLC.)

Early life experiences, including separation from caregivers, can result in substantial, persistent effects on neural, behavioral, and physiological systems as is evidenced in a long-standing literature and consistent findings across species, populations, and experimental models. In humans and other animals, differential rearing conditions can affect brain structure and function. We tested for whole brain patterns of morphological difference between 108 chimpanzees reared typically with their mothers (MR; N = 54) and those reared decades ago in a nursery with peers, human caregivers, and environmental enrichment (NR; N = 54). We applied support vector machine (SVM) learning to archival MRI images of chimpanzee brains to test whether we could, with any degree of significant probability, retrospectively classify subjects as MR and NR based on variation in gray matter within the entire brain. We could accurately discriminate MR and NR chimpanzee brains with nearly 70% accuracy. The combined brain regions discriminating the two rearing groups were widespread throughout the cortex. We believe this is the first report using machine language learning as an analytic method for discriminating nonhuman primate brains based on early rearing experiences. In this sense, the approach and findings are novel, and we hope they stimulate application of the technique to studies on neural outcomes associated with early experiences. The findings underscore the potential for infant separation from caregivers to leave a long-term mark on the developing brain., (© 2021 John Wiley & Sons Ltd.)

In the current study, we examined the number, distribution, and aspects of the neurochemical identities of infracortical white matter neurons, also termed white matter interstitial cells (WMICs), in the brains of a southern lesser galago (Galago moholi), a black-capped squirrel monkey (Saimiri boliviensis boliviensis), and a crested macaque (Macaca nigra). Staining for neuronal nuclear marker (NeuN) revealed WMICs throughout the infracortical white matter, these cells being most dense close to inner cortical border, decreasing in density with depth in the white matter. Stereological analysis of NeuN-immunopositive cells revealed estimates of approximately 1.1, 10.8, and 37.7 million WMICs within the infracortical white matter of the galago, squirrel monkey, and crested macaque, respectively. The total numbers of WMICs form a distinct negative allometric relationship with brain mass and white matter volume when examined in a larger sample of primates where similar measures have been obtained. In all three primates studied, the highest densities of WMICs were in the white matter of the frontal lobe, with the occipital lobe having the lowest. Immunostaining revealed significant subpopulations of WMICs containing neuronal nitric oxide synthase (nNOS) and calretinin, with very few WMICs containing parvalbumin, and none containing calbindin. The nNOS and calretinin immunopositive WMICs represent approximately 21% of the total WMIC population; however, variances in the proportions of these neurochemical phenotypes were noted. Our results indicate that both the squirrel monkey and crested macaque might be informative animal models for the study of WMICs in neurodegenerative and psychiatric disorders in humans., (© 2021 Wiley Periodicals LLC.)