Author Archives: Sofia Pedro

Primate brain folding

A recent work, analyzing the development and evolution of the primate cortical folding, evidences two separate folding processes of the neocortex. Namba and colleagues examine two subtypes of neocortex, the dorsal isocortex, defined as the portion of neocortex limited laterally by the lateral fissure (LF) and medially by the cingulate sulcus (CiS), and the proisocortex within these same boundaries, comprising the insular cortex and the cingulate cortex, respectively. Their sample was composed by three to five specimens from 13 different primate species, including two great apes (humans and chimpanzees), two Old World monkeys, four New World monkeys, one tarsier, one galago, and three lemurs. For each specimen they analyzed five comparable coronal sections. They measured the gyrencephalic index (GI) as the ratio of the length of the inner to outer cortex contours, and calculated the LF score as the ratio of the LF greatest depth to the maximum width of the hemisphere. Then they analyze the relationships between LF score, and the GI values for the dorsal isocortex, the cingulate and insular cortices, and the neocortex, which included the three cortices and the temporal isocortex. To provide an evolutionary perspective, they reconstruct GI and LF score values for the primate ancestors. Furthermore, they examine the timing of folding in a longitudinal sample of humans and long-tailed macaques, and the folding differences in human lissencephalic patients, for a developmental and genetic overview. The proisocortex showed a similar GI across the sample, and the reconstructed ancestor LF scores were in the same magnitude as those of the 13 present-day primates. Conversely, the degree of folding of the dorsal isocortex differs across the species, and between the ancestors and the extant species, increasing with increasing folding of the neocortex. Furthermore, their analyses also revealed that  LF and CiS appear earlier in development, while the dorsal isocortex starts to fold later. This portion of the cortex is also the most affected in human lissencephaly, as the LF, and CiS to a lesser degree, are still detectable in all grades of malformation. Hence, the authors conceptualize the folding of the neocortex as two distinct and sequential processes. The conserved folding occurs earlier in development, at the boundaries between the proisocortex and the dorsal isocortex, and involves the formation of the LF and CiS. The evolved folding occurs within the isocortex, after the onset of the conserved folding. Moreover, the authors suggest these two processes might be influenced by different cellular mechanisms, with neuron production contributing more to the conserved folding, and neuron migration to the evolved folding, a matter deserving further investigation.

 

Sofia Pedro

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Neonate folding patterns

Duan and colleagues developed a new computational method for automatic detection of patterns of cortical folding in large datasets. This method extracts multiple features that characterize the folding patterns, such as sulcal bottoms and gyral crest curvatures. Then, an overall similarity matrix is calculated that contains information on shared patterns and individual variation. Finally, the subjects are clustered on groups that represent a common folding pattern. The authors show their method is more efficient than previous ones in detecting folding patterns and clustering subjects into affinity groups. They validate its reproducibility and reliability in two main samples. They demonstrate the application of their methodology on a large sample of 595 healthy neonate brains, to characterize folding patterns in newborns. Then, they compare their results to a dataset of adult brains from the Human Connectome Project. They focus on four cortical regions, the superior temporal gyrus (STG), the inferior frontal gyrus (IFG), the cingulate cortex, and the precuneus, considering both sex differences and hemispheric asymmetries. Overall, the typical folding patterns of infants were consistent with those of adults, evidencing that cortical folds are largely established from an early age. On the other hand, some differences were also identified. For instance, four folding patterns were recognized in infant STG, while adults have an extra pattern. In contrast, one of the neonates’ IFG pattern is absent in adults. In both samples, there are sex differences in the proportions of some of the folding patterns of STG, IFG, and cingulate cortex. Hemispheric asymmetries were observed in the cingulate and STG, being more significant in the latter, which the authors suggest might reflect language lateralization. Considering the precuneus, their method revealed three main gyral patterns which were not associated with sex differences or hemispheric asymmetries. These gyral patterns appear to be mainly grouped based on the presence of either a gyral structure (patterns 1 and 2, more frequent) or a deep sulcus (pattern 3) in the middle of the precuneus. According to the authors, these groups are similar to the ones described in a previous study by our lab on a sample of adult healthy brains.

Sofia Pedro


Brain regional scaling

Reardon and colleagues recently published a study on the variation of human brain organization and its relationship with brain size. Using neuroimaging data from more than 3000 individuals they calculated the local surface area and estimated the areal scaling in relation to the total cortical area in order to generate a reference map for areal scaling in cortical and subcortical structures. By using three separate cohorts, three different platforms of image-acquisition, and two distinct imaging processing pipelines, they obtained the same results. Regions with positive scaling, i.e. which area increases with increasing total cortical size, were found with the prefrontal, lateral temporoparietal, and medial parietal cortices, whereas the limbic, primary visual, and primary somatosensory regions showed negative scaling. These patterns of cortical area distribution relatively to normative brain size variation were also reproduced at the individual level in terms of proportion, as, for instance, areas of positive scaling regions were positively correlated with the total cortical area. These patterns of areal scaling distribution are also comparable with patterns of brain expansion during human development and primate evolution (humans vs. macaques). In terms of cytoarchitecture, the regions of positive scaling were concentrated within association cortices, such as the default mode, dorsal attention, and frontoparietal networks, while the negative scaling regions were found within the limbic network. The association of areal scaling patterns with known patterns of mitochondria-related gene expression suggests these regions that are expanded in larger brains might differ in their metabolic profile. The authors concluded that the similarity of the areal scaling maps across development and evolution, and at the individual level, suggests a shared scaling gradient of the primate cortex. Larger brains tend to preferentially expand association cortex, specialized for integration of information, which might point to a need for an increase of the neural subtracts, such as dendrites or synapses, in order to maintain or enhance brain function in an expanded brain. Further study designs are required to investigate the relationship between cortical areal patterns and brain function.

Sofia Pedro


Woolly mammoth brain

Endocranial casts are usually the only resource for studying brain gross anatomy of an extinct species. However, sometimes, a frozen mummy can add information not only on the cortical features but also on the internal structures of the brain. Some years ago, Anastasia Kharlamova and Paul Manger published a study on the mummified brain of a Pleistocene woolly mammoth. This Yuka woolly mammoth specimen, dated approximately to 38,000 years ago, was determined to be an adolescent female aged between 6 and 9 years. Its mummified brain is unique in the state of preservation, allowing access to its external and internal morphology through the use of CT imaging techniques. Furthermore, it gave the opportunity to compare mammoths with extant African elephants’ brain, in order to characterize Elephantidae brain evolution, by determining whether elephant-specific features were already present in this specimen. The authors first compared the brains of the two species in terms of overall organization, concluding the Yuka mammoth displays the typical structure of the Elephantidae family. Direct volume comparisons were possible only for the structures which borders were clearly visible on the CT scans. The brain volume of the Yuka mammoth shrank during mummification, due to dehydration, and occupies only about 55% of the endocranial volume. Therefore, the calculated structure masses had to be corrected for such shrinkage. Moreover, due to differences in tissue fat composition, this shrinkage was heterogeneous, differing between hemispheres and between these and the cerebellum, which showed the least shrinkage. Based on subdural volume and on regression equations using extant mammals, the brain mass was determined to range between 4,230 and 4,340g. Given the average brain mass of an adult female elephant is only 300 to 400 g heavier, and that this specimen is immature, the values appear to be close to what would be expected for an adolescent woolly mammoth female. The size of the corpus callosum was also similar to that of female African and Asian elephants suggesting that, like elephants, mammoths also displayed sexual dimorphism in this structure. The comparable size of the amygdala suggests a similar organization of the limbic system, and the similarity in size and organization of the cerebellum point to a similar role in control of the trunk. This further indicates the Elephantidae family holds the largest cerebellum of all mammals, and that the cerebellar sensorimotor integration and learning movements of the trunk is a feature of this family. As the Elephantidae brain structure seems to be evolutionarily conservative, it can be assumed that the woolly mammoth could have achieved the same cognitive capacities as the extant elephants. However, further predictions of behavior and specializations would need a more detailed histological examination, which was not possible in the Yuka specimen. Nonetheless, this study provided an exceptional glimpse into the brain of an extinct species, and helped extending the understanding of the Elephantidae family.

 

Sofia Pedro


Cranial vault thickness in South African Australopiths

In a recent paper, Beaudet and colleagues analyze the cranial vault thickness of StW 578, a partial cranium of Australopithecus not yet assigned to a species. The authors explore the utility of cranial vault thickness and of the organization of the diploe and cortical tables as potential diagnostic criteria for hominin species. For that, they also analyze a comparative sample including other South African Late Pliocene-Early Pleistocene fossils, extant humans, and chimpanzee specimens. Fossils include specimens of Australopithecus and Paranthropus recovered from Sterkfontein, Swartkrans, and Makapansgat sites. Based on cranial landmarks, the authors defined homologous parasagittal and coronal sections on the CT scans, preferentially on the right hemisphere, which is better preserved in StW 578. The thickness of the diploe, the thickness of the inner and outer cortical tables, and the total thickness were measured automatically in various points sampled throughout the length of the sections. The proportion of each layer was computed by dividing the thickness by the surface area calculated between two successive points. Specimens that preserved only the left side were used for qualitative comparison. Results emphasize differences between Australopithecus and Paranthropus. The former genus tends to have thicker vaults, with a larger proportion of the diploic layer, while the latter tends to have thinner vaults, with a larger proportion of the inner and outer tables. The distribution of thickness also differs, as StW 578 and other Australopithecus crania from Sterkfontein display disproportionately thicker frontal and posterosuperior parietal regions, while Paranthropus (SK 46) and extant chimpanzees have thickest regions on cranial superstructures (supraorbital and occipital tori). As the authors suggest, thickening of the cranial vault in frontal and parietal regions needs further investigation, as to unveil a possible correlation between bone thickness and brain anatomy. Moreover, as the increase in thickness is associated with an increase in diploe proportions, variation in this layer might indicate physiological (thermoregulation) or biomechanical differences between Australopithecus and Paranthropus. In sum, cranial vault thickness patterns of StW 578 are equivalent to those of other specimens from Sterkfontein (StW 505 and Sts 71). The presence of a Paranthropus-like pattern in two of the three Mangapansgat specimens further indicates the presence of different morphs or species of Australopithecus in this site. This methodology and results provide a fine base for further studies on the taxonomic significance of the cranial vault thickness. The authors suggest beginning by including more Paranthropus specimens, and by evaluating chronological, geographic, and taxonomic variation.

 

Sofia Pedro


Seasonal brain changes

As we already discussed, small mammal species with short life spans and high metabolisms which experience seasonal fluctuation of resources tend to undergo seasonal changes in skull size and morphology. More recently, Lázaro et al. examined how this seasonal variation affected brain size and organization in the common shrew (Sorex araneus). They collected specimens in Southern Germany, covering all seasons and the whole lifespan of the shrew, which is about 18 months. The sample was divided into three age groups: summer juvenile, winter subadult, and spring-summer adult (sexually mature). Right hemispheres were used to investigate the volumes of the different brain regions, and the left hemispheres for examining neuron morphology. They confirmed the patterns of seasonal volume variation, and observed there were differences between brain regions and between sexes. The overall volume decrease from summer to winter was more pronounced in females, while spring regrowth was similar for both sexes, thus resulting in adult sexual dimorphism with females having smaller brain volumes. Regarding the brain regions, most significant changes were observed in the hypothalamus and the thalamus, both in the winter decrease and spring regrowth. Neocortex and striatum (mostly caudoputamen) volumes decreased in winter but did not regrow in spring. Cerebellar volumes were smaller in females during winter, but reached the same volumes as males during spring regrowth. According to the authors, as the volume reduction from juveniles to subadults occurs before winter, it is more likely genetically encoded than a direct result of temperature or resources fluctuation. Furthermore, the independent variation of the different brain regions suggests a mosaic adaptation of each structure to the cognitive requirements and energetic limitations of each season. Other explanations for the different patterns of variation between the different regions might be associated with differences in energetic demands and in the potential for plasticity between brain structures. However, the authors could not find correlations between seasonal volume changes and functional demands, developmental timing, or metabolic consumption of the different brain regions. They conclude the variation in each brain structure might be influenced by functional adaptations and plasticity to different degrees. The authors also registered the variation in neuron size and morphology in three regions. The caudoputamen showed a decline in dendritic length and volume, in soma size, and in spine number and density, from juvenile to adult. The somatosensory cortex displayed only decline in soma size from summer to winter and in spine density from winter to adult. In the anterior cingulate cortex there was a reduction in soma size from juvenile to adult but in dendrite volume only from juvenile to subadult. These results cannot explain adequately the observed volumetric changes in the respective regions, and other factors that might affect volume, such as the space between cells and neuron density, should be considered in further studies. Moreover, changes in axonal innervations and myelin, and in the density of microvessels should be considered as these can also influence energetic costs.

Sofia Pedro


Parietal lobes and tool use

The parietal lobe has a unique central location in the brain, and it is involved in higher cognitive functions. Investigating its functions and connectivity is essential to understand its role in uniquely human abilities. Two recent works have put emphasis on the importance of the parietal lobe for tool use.

Catani and colleagues investigated the intralobar parietal connectivity in human and monkey brains, using diffusion imaging tractography. In general, the patterns of white matter connectivity are similar in both species, although with some differences for areas that are distinct in humans. The larger tract connects the superior parietal lobule (SPL) to the angular and supramarginal gyri of the inferior parietal lobule, within the IPS. The authors suggest it might act to mediate the interaction between the two lobules during object manipulation, and to coordinate both dorsal and ventral visuospatial networks. The second and third larger tracts link the postcentral gyrus to the inferior parietal lobule and to the SPL, respectively. These might transmit tactile and proprioceptive information on the body orientation relatively to an object for guiding motor actions and grasp. The connection between the postcentral and the angular gyri was only observed in humans, leading the authors to highlight its role in specific cognitive functions. Particularly, its connections to SPL are key for tool use, mathematical thinking, and language and communication.

Kastner and coworkers reviewed the organization and function of the dorsal pathway of the visual system of monkey and human brains, focusing on the areas of the posterior parietal cortex within and adjacent to the intraparietal sulcus (IPS). Monkeys and humans have diverged in the functional contributions of the IPS since their last common ancestor, as some functionally-defined areas that are located within the IPS in monkeys have been partially relocated outside this sulcus in humans. The authors suggest this relocation might be due to expansion for accommodation of human-specific abilities, such as tool use. They hypothesize that humans might have developed a derived and advanced tool network from the modification of the macaque circuit for object manipulation. First, the human dorsal vision pathway must provide object shape information regardless of size and viewpoint, facilitating object recognition and mental manipulation. Second, object information is integrated with cognitive information such as working memory, allowing maintaining the information over a period of time. Finally, humans have areas that respond specifically to tool use, some of which also integrate frontal and temporal networks involved in action recognition and semantic knowledge related to tools and actions, respectively.

Both studies point at the parietal lobes and visuospatial integration as key elements for human cognitive capacity, as suggested by evidence in paleoneurology, evolutionary neuroanatomy, and cognitive archaeology.

 

Sofia Pedro


Skulls and brains in reptiles and birds

In a recent paper, Fabbri et al analyzed the relationship between brain and cranial vault shape in the transition from reptiles to birds. To assess the evolution of this relationship they used a broad sample including Aves, Lepidosauria, Crocodylia, Archosauria, and Reptilia. To assess developmental differences they included an ontogenetic sample of Alligator mississipiensis and Gallus gallus. The results showed that the relationship between the vault bones and the brain is conserved across these taxa, with the frontal bone positioned over the forebrain and the parietal bone over the midbrain or over midbrain and posterior forebrain. Nonetheless, they observed some shape variations, namely on the relative sizes of the frontal and parietal bones and in the position of the fronto-parietal suture relative to the forebrain-midbrain boundary. These two structures are significantly correlated, with the fronto-parietal suture being either anterior to (e.g. stem reptiles) or nearly aligned with (e.g. crown birds) the forebrain-midbrain boundary. In terms of ontogeny, chickens have a shorter ontogenetic trajectory than alligators, as the brain and skull of embryos are similar to the adult ones. The brain and skull of alligators develop with negative allometry, with the brain relatively large in early stages but becoming relatively small during growth. Conversely, the skull and brain of chicken grow with positive allometry, and the authors suggest the brain should be considered peramorphic in Aves. Overall the results stress the important role of the brain in shaping the cranial vault. The authors wonder whether the intimate relationship between brain and frontal and parietal bones is the key for the conservation of the cranial vault across vertebrates.

Sofia Pedro


Primates brain shape

We have published one more paper on the morphology of the precuneus, this time featuring a sample of non-human primates, in collaboration with James Rilling and Todd Preuss from the Emory University (Atlanta, USA). Modern humans have a much larger precuneus than chimpanzees both in absolute and relative size. Taking into account the large brain size in our species, we investigated the midsagittal morphology in non-human primates as to test whether precuneus proportions are influenced by allometric factors. We did a geometric morphometric analysis on a total of 42 MRIs from the National chimpanzee brain resource database, including 5 species of apes and 4 species of monkeys. A first analysis, conducted on the species averages, showed that the main pattern of midsagittal variation involves the general shape of the braincase, which might be due to cranial constraints rather than to changes in proportions of specific brain regions. This main shape pattern separates monkeys from apes, as the former display flatter, elongated brains (with capuchins being the flattest), while the latter exhibit rounder brains with frontal bulging (especially orangutans). This morphological variation correlates with brain size, except for gorillas (which brain is large but elongated), and gibbons (which have smaller but round brains). A second analysis was conducted only on chimpanzees and macaques, to compare two species with different brain size. In neither case the proportions of the precuneus displayed major differences between species or size-related changes. However, as in humans, precuneus size is very variable within each species, suggesting a remarkable plasticity. Overall, the results suggest that precuneus expansion in modern humans is a species-specific characteristic of our species, rather than a simple consequence of increase in brain size. Further studies should address the histological and functional processes involved in this morphological change.

Sofia Pedro


Eye-brain spatial relationship

We have just published a new study on the spatial relationship between visual and endocranial structures in adult modern humans, chimpanzees, and fossil humans. The survey was conducted in collaboration with Michael Masters from Montana Tech (USA), who previously hypothesized that, in modern humans, the positioning of the orbits below the frontal lobes coupled with a reduced face could result in spatial conflict among ocular, cerebral, and craniofacial structures. This could lead to vision problems, such as myopia. In addition, another study evidenced that eye and orbit dimensions have a stronger correlation with the frontal lobes, rather than with the occipital lobes, indicating that the ocular structures can be more constrained by spatial (physical) than by functional (vision) relationships. In this study we used geometric morphometrics to investigate the longitudinal (antero-posterior) spatial relationships between orbito-ocular and endocranial structures. First, we addressed the the position of the eye relatively to the frontal and temporal cortex, on a sample of 63 modern humans’ MRIs. Second, we addressed the spatial relationship between orbital and endocranial structures on a CT sample comprising 30 modern humans, 3 chimpanzees, and 3 fossil humans (Bodo, Broken Hill 1, Gibraltar 1).

The results of the MRI analysis show that in adult modern humans the main pattern of shape variation deals with the antero-posterior position of the eye relative to the temporal lobes. Individuals which eyes are closer to the temporal lobes exhibit rounder frontal outline and antero-posterior shorter eyes, indicating a possible physical constraint associated with the spatial contiguity between the eye and the middle cranial fossa. A second pattern describes the supero-inferior position of the eye, relatively to the frontal lobe. Also in this case, proximity is apparently associated with slight changes in eye form. Individuals with larger volumes of the frontal and temporal lobes tend to have eyes located more posteriorly, closer to the temporal lobe, although with no apparent change in the shape of the eye. These results partially support Master’s hypothesis, suggesting reciprocal spatial patterns influencing brain and eye form.

When analyzing orbits and braincase through CT data, the main intra-specific variation among modern humans concerns the orientation of the orbit, not the position. Nonetheless, analyzing humans, apes, and fossil hominids all together, the main differences deal with the distance between orbits and braincase: they are separated in chimps, overlapped in modern humans, and in intermediate position in fossils. In this case, fossils belong to the hypodigm of Homo heidelbergensis. Modern humans are characterized by larger temporal lobes when compared with other living primates, and longer middle cranial fossa. The proximity with the eyeballs due to face reduction can stress further a morphogenetic spatial conflict between orbits and brain. Next step: 3D analyses, ontogenetic series, and vision impairment.

Sofia Pedro