Author Archives: 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

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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


Microgravity and sensorimotor function

Space missions can have adverse effects on astronauts, such as the already-mentioned vision deterioration and cognitive impairment. Spending a long time on space can also impact sensorimotor function. Koppelmans et al. have recently investigated the influence of microgravity environment on sensorimotor performance and brain structure. They conducted a longitudinal study with a group of male subjects remaining in a 6-degrees head down tilt bed rest (HDBR) position, an analog environment to study the effects of spaceflight microgravity, during 70 days. MR images were collected before, during, and after HDBR, to explore changes in gray matter (GM) volume, and functional mobility and postural equilibrium tests were conducted pre- and post-HDBR, to check sensorimotor performance. For control, they used data from other subjects who had completed the same measurements at four different times over 90 days for another study, not being exposed to HDBR. Relative to controls, the HDBR subjects showed widespread changes in GM volume, as the percent of brain volume, from pre- to the last assessment during HDBR. More specifically, GM volume increased in the posterior parietal region and decreased in the fronto-temporal regions, and these changes are strongly correlated. The sensorimotor performance was decreased in HDBR subjects from pre- to post-HDBR, as they needed more time to complete the test, while controls showed no difference in performance. Following the HDBR period, both GM volume and sensorimotor changes started to recover, though not totally 12 days later. Regarding the association between brain and behavior, researchers found that larger increases in GM volume in precuneus and pre- and postcentral gyri correlated with better balance performance, though not significantly after Bonferroni correction. They propose these changes in GM volume might reflect cortical plasticity as an adaptive response to alterations in somatosensory input caused by HDBR position. The observed patterns of GM change could also be explained by alterations in intracranial fluids distribution and pressure due to posture, though this hypothesis would need further examination. The authors conclude their findings match the sensorimotor deterioration observed in astronauts, but are also of interest for individuals who are temporarily or permanently confined to a bed and will probably experience the same GM and sensorimotor alterations.

Sofia Pedro


Cortical and scalp development

In a recent study, Tsuzuki and colleagues analysed the co-development of the brain and head surfaces during the first two years of life using a sample of 16 infant MRIs, aged from 3 to 22 months. First, they digitized a set of cortical landmarks defined by the major sulci. Then they determined the position of cranial landmarks according to the 10-10 system, a standard method to place electrodes for electroencephalography, using  nasion, inion, and the pre-auriculars as a reference. Besides analysing the spatial variability of the cortical and scalp landmarks with age, they compared the variability of the cortical landmarks to the 10-10 positions, in order to evaluate the validity of the scalp system as a reference for brain development. For that, they transferred a given cortical landmark to the head surface by expressing its position as a composition of vectors in reference to the midpoint between the two pre-auriculars and to the three neighbor 10-10 points. The scalp-transferred landmarks were then transformed to the scalp template of a 12-month-old infant and depicted in reference to the 10-10 system.

Age-related changes in the cortical landmarks were most obvious in the prefrontal and parietal regions. As the brain elongates, the frontal lobe shifts anteriorly and the precentral gyri widen. In addition, the intraparietal sulci and the posterior part of the left Sylvian fissure move forward, suggesting relative enlargement of the parietal region in the anterior direction. The same result was obtained by our team by analyzing cranial and brain landmarks in adults: larger brain size is associated with a relative forward position of the parietal lobe. The scalp showed relative anteroposterior elongation and lateral narrowing with growth. Regarding the contrast between the cortical landmarks and the 10-10 system, the authors observed that the variability in the position of the former was much smaller than the area defined by 10-10 landmarks, indicating this system can be useful to predict the underlying cortical structures. Hence, they conclude that the changes in brain shape during development are well described by cortical landmarks and that the relative scalp positioning based on the 10-10 system can adjust to preserve the correspondence between the scalp and the cortical surfaces.

 

Sofia Pedro


Brain partition scaling

A group coordinated by Dr. Vera Weisbecker examined whether the evolution of mammalian brain partitions follows conserved developmental constraints, causing the brain to evolve as an integrated unit in which the partitions scale with brain size. According to this ‘late equals large’ hypothesis, the timing of neurogenesis predicts the size of the partition such that later and more extended neurogenesis produces larger partitions due to the production of more neural precursors. In order to investigate the impact of neurogenesis on patterns of brain partition growth, the volumes of the whole brain and major partitions were reconstructed from soft-tissue diceCT scans of three marsupial species, including individuals with ages ranging from 1 day to adulthood. They tested three hypotheses consistent with a conserved brain partition growth: H1 postulates that partition scaling during development reflects the evolutionary partition scaling, and thus growth patterns should be uniform between species; H2 assumes that a neurogenesis-driven pattern of partition scaling is predictable from adult brain size, i.e. brain partitions scale with brain size; and H3 states that growth with age might differ between species according to brain size and/or neurogenetic events. Regressions of log partition volume against log rest-of-the-brain volume (whole-brain volume minus partition volume) showed significant interspecific differences in slopes and intercepts of most brain partitions, indicating diverse scaling patterns between species, which could not be predicted by adult brain size, as the smallest-brained species had intermediate slope to the other two.  Growth curves of log partition volume against age were similar in all partitions within-species, but differed between species, particularly in growth rates, with the species with intermediate brain size having slower rates than the other two. Differences in growth patterns do not seem to be related to neurogenetic schedule as largest partitions are not especially late in their development and important maturation processes, like eye opening, occur closer to the end of the growth phase. Thus, none of the hypotheses are supported by these results, challenging the conserved neurogenetic schedules behind the evolution of mammal brain partitions. Moreover, the authors found high phylogenetic signal in brain partition scaling, revealing that a large part of the scaling relationship between brain and partition volumes is explained by phylogeny, which is more in agreement with a mosaic evolution of brain partition sizes, stressing its biological meaning and the level of mammalian brain plasticity. However, the intraspecific regular partition growth curves led the authors to contemplate the existence of an early brain partition pattern regulated by regional gene expression, and propose that further studies of brain partition evolution should integrate developmental neuromere expression models, neuron density, and patterns of neuron migration.

 

Sofia Pedro


Structural MRI artifacts

Magnetic resonance imaging (MRI) is a valuable and increasingly used method for studying brain anatomy as it allows large-scale, high-quality in vivo analyses. However, some artifacts might influence the digital results, and thus require cautious interpretation. In a recent review, these issues are addressed along with possible solutions. First, we need to keep in mind that the images acquired are not mere photographs of the brain, but reflect some biophysical properties of the tissues, by measuring the radio-frequency signals emitted by hydrogen atoms (present in water and fat) after being excited by magnetic waves. Thus, MRI is an indirect analysis of the brain anatomy and depends greatly on specific tissue properties. Second, researchers can choose from a variety of methods, depending on the aim of the survey. Macrostructure, i.e. the size and shape across voxels, can be studied through manual volumetry or automatic segmentation, voxel- or deformation-based morphometry, surface- based algorithms, or diffusion tractography. Microstructure, i.e. within-voxel contents, is usually analyzed through diffusion MRI, but also magnetization transfer imaging, or quantitative susceptibility mapping.

When making inferences on the biological significance of the outputs, the researcher must account for the possible digital artifacts. These can occur both during image acquisition and processing and can be subject-related and methodological-related. A common problem is subject motion, which might contaminate or influence the results, as the amount of motion varies with other factors influencing brain changes (age, sex, and disease status), or can even correlate with a specific effect being studied. For instance, motion induces gray matter reduction, which might be perceived as brain atrophy. Subject motion is unavoidable, but its influence can be reduced by using a motion detector during acquisition, or by estimating the amount of motion allowing statistical adjustments, also useful to  detect outliers. The difficulty in manipulating the magnetic and radio-frequency fields might also introduce deformation. The main magnetic field should be spatially uniform, but it is dispersed by brain tissue while concentrated by air. This can be partially compensated by applying additional fields. The radiofrequency field is not homogeneous, which affects MRI contrast and intensity. Combining multiple transmit coils might help reduce this caveat, although the contribution and sensitivity of each coil must be taken into account when processing the image.

A particular case that can affect estimates of cortical volume and thickness is the difficulty in discriminating the dura and gray matter due to the similar intensity and anatomical proximity. In this case,  MRI parameters can be manipulated in order to increase the contrast between these tissues, without reducing the contrast between gray and white matter. Individual variability in folding patterns is a further major issue in voxel-based morphometry studies because it complicates the mapping of correspondences between subjects. Registration might be enhanced by analyzing regions with larger variation to find possible anatomical alterations, aligning cortical folding patterns to locate corresponding areas, and mapping sulcal changes to improve sulci identification. Finally, researchers should continuously keep track of the constant advances and innovations in the field. The authors conclude acknowledging the importance of structural MRI when coupled with other biological information, like genetic expression (Allen Brain Atlas), cytoarchitecture (JuBrain), and cognitive associations (Neurosynth).

Sofia Pedro


Seasonal skull reduction

dechmann-et-al-2017Braincase shrinkage during winter was firstly described in shrews by Dehnel in 1949, and is known as the Dehnel’s Phenomenon. Recently, Dechmann et al. investigated the seasonal size variation in the skulls of shrews (Sorex araneus) and least weasels (Mustela nivalis). They measured skull length and braincase depth on specimens previously collected from a Polish National Park, sampling all seasons. Both species showed an initial juvenile growth until the first winter, followed by shrinkage until spring in the adults, and a subsequent re-grow on the second summer, though never reaching the initial size. Heat maps built from high resolution CT scans demonstrated that size changes also involved changes in shape and in bone thickness, with the thinnest skulls coinciding with the smallest braincase size. Interestingly, these patterns differed between sexes, especially in weasels as only males were observed to re-grow. Despite phylogenetically distant, both species have similar life histories, having short life spans and high metabolisms, and inhabiting an environment with seasonal fluctuation of resources availability. Winter shrinkage would reduce energetic requirements and prepare individuals for the harder conditions, and re-growth during the resources-abundant season would prepare the males for reproduction while females would allocate the energy into caring for the offspring.  The authors conclude these seasonal reversible size changes are genetically fixed and exclusive of animals with such life histories, as an adaptation to extreme environmental conditions. Future investigation shall clarify the potential drivers and consequences of this phenomenon, including how the variation in size affects brain size and reorganization.

Sofia Pedro


Face and cranial base

neauxDimitri Neaux and colleagues have published a series of comprehensive analyses on the influence of the cranial base in facial morphology of humans and apes. In one of the papers, they assessed the integration between the face and the two basicranial modules: the sagittal and the lateral cranial base. They tested the covariation between the three sets of 3D landmarks (face vs. midline base and face vs. lateral base) on modern humans and chimpanzees, separately. Only the correlation between the face and the lateral cranial base was significant, confirming the important role of the lateral cranial base in facial morphology. Though the levels of covariation were comparable, the patterns differed between the two species, as taller faces were associated with wider and shorter cranial fossae in chimps and with longer and narrower cranial fossae in humans. In another article, they assessed the relationship between cranial base flexion, facial orientation, and facial shape in modern humans, chimpanzees, and gorillas. Using 3D landmark analysis, they evaluated the within-species patterns of covariation, confirming the intraspecific relationship between facial structures and base flexion. Base flexion is associated with downward rotation of the facial block in both humans and chimps (confirming previous works) but not in gorillas. On the other hand, an upward rotation of the facial block is associated with anterior face vertical elongation on the three species. In humans, facial elongation is also associated with base flexion, which might have been selected during evolution to match the elongation of the nasomaxillary complex, as proposed before. The authors further tested whether increased base flexion is associated with the shortening of the facial length or with the decrease of facial projection. The relationship between base flexion and facial length was only observed in chimps, while facial projection was not related with cranial base flexion in chimpanzees and gorillas. In humans, contrary to what was expected, basicranial flexion was associated with increasing facial projection, which the authors attribute to sexual dimorphism, as males have increased base flexion and facial projection. Again, the main patterns of correlation differed between the species. Cranial base angle is negatively correlated with facial projection in modern humans, with facial length in chimps, and with the angle between the posterior-maxillary plane and the anterior facial plane in gorillas. As the authors conclude, these differences in the patterns of integration might reflect changes in the structural relationships between the face and the cranial base during hominoid evolution.

Sofia Pedro


Hyena paleoneurology

hyenasA series of works by Sharleen T. Sakai’s group have correlated the proportions of the anterior endocranial region with social behaviour in hyenas. They found that in spotted hyenas (Crocuta crocuta), males have relatively larger anterior cerebrum than females. The relative volume of the anterior endocranial region is also significantly larger in this species when compared to other extant species of hyenas. The spotted hyenas are the most gregarious species, living in large clans, where females are dominant and philopatric, and males disperse and must adapt to the hierarchic system of a new clan. The anterior region of the hyena’s brain comprises mostly the frontal cortex, which mediates social behaviour. The authors hypothesize, in the light of the social brain hypothesis, that the development of the frontal region in this species, and particularly in males, might have been enhanced by the need for a larger behavioural flexibility in their complex social environment. More recently, Joan Madurell-Malapeira and his colleagues compared the endocasts of two extinct spotted hyenas (C. spelaea and C. ultima) with those of extant species. The fossil specimens have similar morphology to that of C. crocuta, but less developed anterior portion of their endocranium. The authors therefore propose this feature to be an autapomorphy of C. crocuta. Consequently, the social and foraging behaviour of these fossil species are presumably less specialized, and this might contradict some speculations about competition between hyenas and humans during Pleistocene.

Sofia Pedro