Author Archives: sofiappedro

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


Brain shape and encephalization in birds

marugan-lobon-et-al-2016Encephalization quotients (EQ) have been extensively used to characterize brain evolution, but this univariate metric only includes information on relative size. Marugán-Lobón and his colleagues recently analysed the association between endocranial shape changes and EQ by applying geometric morphometrics to a sample of modern bird endocasts. A Principal Component Analysis accounting for phylogenetic history showed that the bird endocasts varied essentially in the relative expansion of the forebrain and in the degree of flexion of the braincase. The distribution of the specimens in the morphospace has a phylogenetic structure, with morphological affinity between close evolutionary clades, particularly the landbirds, which display larger forebrains. Size explains 10% of the shape variation. EQ accounts for changes in relative forebrain expansion, with larger EQs associated with larger forebrains. A second study was computed correcting for phylogeny, i.e. computing regression analyses on the phylogenetic independent contrasts of shape and size against EQ. When allometric and phylogenetic signals were removed, shape variation was mostly associated with the degree of flexion of the endocasts, and EQ was not significantly correlated with these morphological changes. The authors conclude that, excluding the general effect of size, EQ does not explain shape differences among birds’ endocasts. Therefore, other factors are probably responsible for brain variation in birds.

Sofia Pedro


Precuneus: folding and metrics

Pereira-Pedro and Bruner 2016_1 This month we have published a study featuring the cortical extension and anatomy of the precuneus, dealing with its metrics as well as with its sulcal pattern. The analysis was based on a MRI sample of 50 adult humans from both sexes. Our previous works concerned the variation, position, and surface, as well as the phylogenetic differences in the midsagittal plane. Instead, in this survey metrics was assessed on the coronal plane, “cutting” the precuneus in its anterior, middle and posterior sections, taking into account its curvature. The lateral (inner) extension of the precuneus was measured along the subparietal sulcus and its height was measured from the subparietal sulcus to the endocranial wall. Then a set of 10 two dimensional landmarks were digitized on the middle section along the outline of the parietal lobe, to analyze the correlation between outer brain profile and inner precuneus dimensions. We found that, on average, the precuneus extends 14 mm laterally and 36 mm vertically. It is wider on the anterior and middle sections, and usually larger on the right hemisphere, possibly due to the length of the fold (surface area) rather than to the thickness of the grey matter. The precuneus height influences the outer brain morphology (vertical stretching), but the subparietal size apparently has no influence on the external outline. Therefore, at least the former trait could be investigated in paleoneurology, by indirect inference on the inner dimensions as evaluated through their external effects. The lateral (parasagittal) surface of the upper parietal lobules seems to be unrelated to the size of the precuneus. Therefore, when a change of these areas is detected (like in Neandertals) the intraparietal sulcus is a better candidate as the cortical element involved in the morphological variations.

Pereira-Pedro and Bruner 2016_2

The sulcal pattern was analyzed on the average density projection of the 5 most sagittal stacks (5 mm of the cortex), a thickness which displays most of the sulcal features. Three characteristics were taken into consideration: the connections of the subparietal sulcus, the connections of other sulci in the precuneus, and the general sulcal scheme. Some of these features have been analyzed in other surveys, but  the consideration of other folds beyond the subparietal one is specific of this study. Roughly half of the precuneus sulci that reach the external surface are not linked to the subparietal sulcus. Contrary to other studies which found higher frequencies of an H-like pattern of the subparietal sulcus, we found a larger proportion of an inverted-T pattern (subparietal sulcus connected with one precuneus sulcus). The differences between studies might be due to random effects of the samples, because of the relevant individual variability of these traits. The left hemisphere displays more sulci reaching the external surface while the right hemisphere displays deeper folding. The anterior area shows more sulcal complexity than the posterior one. There seems to be no relationship between the size of the subparietal sulcus and its folding pattern, and these characteristics might be hence influenced by genetics or folding biomechanics.

Sofia Pedro


Notoungulata endocasts

Dozo and Martínez 2016Notoungulata is an extinct order of ungulates, endemic from South America. It has two main suborders: Toxodontia, including the large-bodied ungulates, and Typotheria. Researchers from Argentina have described the endocasts from two species of Notohippids, a family from the South American Oligocene that is included in the Toxodontia group. The endocasts from Rynchippus equinus and Eurygenium latirostris were virtually reconstructed from CT scans and compared to other fossil and extant ungulates. Both endocasts were similar in size and in their overall shape, proportions and sulci morphology. They fitted into the general “design” of the Toxodontia endocasts, which have the most complex surface within the Notoungulates, with pronounced telencephalic flexure, a developed Sylvian sulcus, and a bulging temporal lobe. These features are also similar to those displayed by the rabbit-like Typotheria group, although Notohippids had larger frontal region. In contrast, extinct and extant ungulates display a different endocast morphology, without prominent Sylvian and temporal regions. According to the authors, functional interpretations for the expansion of the frontal region and the Sylvian and temporal areas in the Notohippids can suggest an increase in the snout sensitivity and an auditory specialization, respectively.

Sofia Pedro


Brain gyrification and simulations

The advantages of brain gyrification are well established, but the mechanisms behind this process are yet matter of discussion. However, early this month, a group of researchers published two models for brain gyrification based on the mechanical stress generated by the differential growth of the cortical layer. They created a physical model of a brain in three steps: (1) 3D printing a plastic replica from a MRI of a smooth fetal brain; (2) build a silicon negative mould to cast the core of a gel brain, which would represent the white matter; and after cooled, (3)  deposited the same gel polymer in the surface of the core to form the cortical layer. These polymer layers act as elastic solids. The mimicking of fetal brain growth was accomplished by placing the gel brain in a substrate of hexanes that would cause swelling and differential growth of the outer cortical layer, in respect to the core of the model. Starting from the same MRI, they also built a numerical model based on finite element and parameters like cortical thickness, brain growth and tissue stiffness, creating functions for folding and unfolding simulations. The combined results of the physical and numerical simulations showed that the pattern of gyrification depends on the overall shape of the brain, and the primary sulci are formed perpendicularly to the largest compressive stress. Their models are robust and reproducible, capturing the main gyral scheme and even account for variability and hemispherical differences. Furthermore, when comparing the simulated brain to a real one, they were able to find a correspondence with all the primary folds.

Sofia Pedro


Non-human primate microCT dataset

Copes et al 2016A new dataset of non-human primate microCT scans is now available. The original specimens (59 species) belong to the Museum of Comparative Zoology at Harvard University. The dataset includes 431 skulls of adults and juveniles (and also some postcranial elements) with resolutions between 18 and 125 microns, depending on the size of the specimen. The scans can be freely downloaded, under registration, from the MorphoSource website, which is an open-access archive of 3D data. From the MorphoSource front page you can easily browse by Institutions, and access the specimens. In addition, the authors have also provided a dataset of landmark configurations digitized from the skull sample, available from Dryad Digital Repository.

Sofia Pedro


Microcephaly and Zika virus

microcephalyRecently Brazil has declared state of emergency due to an epidemic of newborn microcephaly. Children with microcephaly have significantly smaller head circumference than the mean for their age and body size. It results from abnormal brain development before birth or during infancy that can be caused by genetic (e.g. Down syndrome) or environmental factors affecting development, for instance craniosynostosis, malnutrition, and infection. Children with this condition may be cognitively impaired and need special medical care throughout their lives. During 2015 Brazil has been registering a drastic increase in the cases of microcephaly, mainly in the northeastern states. For instance in Pernambuco there was 141 cases while the mean is around 10 per year. Coincident with this epidemic, Brazil was also affected by a Zika virus outbreak firstly detected in late April and confirmed in 14 states by November. This virus was first identified in the 1940’s in Uganda, and it is now distributed throughout several tropical countries. It is transmitted to humans by bites of infected mosquitoes of the genus Aedes, the same that transmit dengue and yellow fever. Because symptoms of infection by Zika virus are mild it has not been given much attention. However the coincidence between the virus outbreak and increased microcephaly incidence in Brazil led to a suspicion that there was an association, further reinforced by the confirmation of the virus during an autopsy of a microcephalic baby.

The relationship between microcephaly and Zika virus is now being investigated and the government is taking steps to control the mosquitoes’ population and to assist the children with microcephaly. This virus may have spread from the French Polynesia, where there was an outbreak in 2013-2014, and where the Zika virus was associated with neurological complications like Guillain-Barré syndrome. If an association between a mosquito-transmitted virus and neurological conditions is confirmed, further measures of prevention must be taken as the area favorable for mosquitoes spreading seems to be increasing.

Sofia Pedro