Spatial-packing in the mouse skull

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Both in ontogeny and phylogeny, anatomical structures interact physically to varying degrees. Jeffery et al. (2020) explored this phenomenon by observing the spatial demands of the brain and masticatory muscles (masseter) in a hypermuscular mouse model and computational simulations. Specifically, they tested the spatial-packing hypothesis. This hypothesis states that, due to the head’s finite capacity, once it is spatially optimized, any physical change in one of its components demands subsequent change in one or more of its neighboring structures. Hence, they tested (1) if masseter growth restricts brain development directly, which predicted a synchronized ontogenetic timing of hypermuscularity and a reduced brain size; and (2) if masseter growth restricts brain development by acting on the surrounding skull (indirectly), which predicted skull markers of brain expansion to be weaker in hypermuscular mice.

Results showed that hypermuscular mice presented, for instance, a decreased facial height. In other words, skull markers of brain expansion were indeed weaker in hypermuscular mice, meaning masseter growth restricts brain development by acting on the surrounding skull. However, while hypermuscular mice presented diminished endocranial volumes at birth, their masseter volumes were normal, meaning that masseter growth does not constrain brain development directly. Furthermore, the authors suggest that the reduced endocranial volumes of hypermuscular mice at birth imply the involvement of more systemic factors. This phenomenon is attributed to a deficient prenatal neuronal growth, which is contended to stem from the metabolic demands of developing a larger masseter later in life. As a concluding remark, Jeffery et al. (2020) state that spatial-packing is best detected later in ontogeny and emphasize the importance of considering genetics in morphological studies. On Jeffery’s webpage you can find more projects on craniofacial ontogeny, evolution and plasticity.

Tim Schuurman


Anatomical organization of the primate skull

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Primate skulls host a series of distinctive anatomical features, such as a reduced number of bones due to bone fusions or losses. In his latest work, Esteve-Altava (2022) uses network theory to evaluate whether this particular anatomical organization of the skulls of primates sets them apart from other mammals. In order to perform this evaluation, the author analyzes specific network properties as proxies for integration — the amount of interconnection among skull bones — and disparity — the degree of variance in the bones’ number of connections. Results reveal that the anatomical organization of primate skulls can indeed be distinguished consistently from the skulls of other mammals. Specifically, primates present a more interconnected skull, which in turn is composed of many poorly connected bones and few highly connected bones. A strong cranial integration implies that the modification of one bone is likely to cause collateral change in adjacent ones. Meanwhile, an increased disparity of connections among bones protects the skull from random, non-targeted, damage (e.g. injury or loss): possessing more poorly than highly connected bones means that random damage is more likely to affect the former.

Esteve-Altava (2022) also investigated how integration and disparity relate to the increase in brain size relative to body size, a feature that is typical of primates. Results show that brain size does influence the anatomical organization of all mammals’ skulls. Several possible explanations are provided for this phenomenon, such as a selective pressure by bigger brains for more robust and protective skulls. However, the effect of brain size on anatomical organization is different in primates and in non-primates, and the cause behind these differences remains inconclusive. To bolster these results, as well as to find the missing pieces, the author urges future endeavors to explore the principles of the skull’s anatomical organization in other mammal orders.

Tim Schuurman


History of the brain’s lobes

According to the current official anatomical nomenclature — provided by the Federative International Programme for Anatomical Terminology (FIPAT) in the Terminologia Anatomica (1998) and the Terminologia Neuroanatomica (2017) —, the cerebrum can be divided into the frontal, parietal, occipital, temporal, insular and limbic lobes. However, this was not always the case. Moreover, the history of the brain’s lobes is severely understudied, which is precisely the gap which Casillo et al. (2019) set out to fill.

SkullBox_5_1Their timeline starts in Ancient History with Alecmeon of Croton and Hippocrates of Kos, who were among the first to attribute cognitive functions to the brain. Erasistratus of Chios then ascribed human intelligence to the number of convolutions of the cortical surface. Unfortunately, despite this early attribution of intelligence to the cerebral cortex, Galen of Pergamon proposed the ventricular system to be responsible for complex brain functions, and his train of thought prevailed for over one thousand years. It was not until the 17th century that Thomas Willis shifted the focus of brain studies to the cerebral cortex again. He proposed that the cortical surface follows a pattern and coined the term ‘lobe’. In 1796, French neuroanatomist Felix Vicq D’Azyr pioneered the use of the word ‘frontal’ when discussing the cerebral lobes. Meanwhile, in Germany, Johann-Christian Reil provided the first description of the insula. Besides providing much detail in their explanations and figures, Casillo et al. (2019) paint a clear picture of the misconceptions and misattributions surrounding the discoveries related to the brain. They explain, for instance, how Greil was the first to describe the insula in 1796, but that Franciscus Sylvius had already depicted it in 1641. Finally, all in France and in less than eighty years, François Chaussier defined the modern boundaries of the frontal, occipital and temporal lobes; Louis Pierre Gratiolet and François Leuret divided the brain into the frontal, parietal, occipital, temporal and insular lobes; and Paul Broca added the missing piece, the limbic lobe.

Tim Schuurman


Cerebrovascular stiffening effect

3Untitled-3Cerebral vasculature is critical to the maintenance of the brain health. Arteries deliver the oxygenated blood, glucose and other nutrients to the brain, and veins carry blood containing carbon dioxide and other waste products back to the heart. The vascular system is also involved in brain thermoregulation. However, the cerebral vasculature may also provide a mechanical protection for the brain when traumatic injury occurs. The cerebral vasculature is several orders of magnitude stiffer than the brain tissue, and, arteries are stiffer than veins. A potential cerebrovascular stiffening effect on brain strains (caused by an external head impact) has been scarcely studied, and with contradictory results. Zhao and Ji (2020) have published a study that aims at investigating the potential cerebrovascular stiffening effect in a head injury. They reanalysed the stiffening effect of cerebral vasculature by incorporating vasculature derived from the latest high-resolution neuroimaging atlases into a re-meshed Worcester Head Injury Model using an embedded element method. They simulated a head injury (sagittal impact) with and without vasculature (taking into account several material properties of the vessels) and then compared the regional strains in the whole brain, cerebrum, cerebellum, brainstem, and corpus callosum. The authors applied refitted non-linear material models that should represent the average dynamic tension behaviours of arteries and veins. The results showed that inclusion of vasculature reduced regional brain strains by ~13–36%. Moreover, the vascular stiffening effect seem to be mild for the whole brain but significant locally, especially in regions where major arteries reside, such as the brainstem and corpus callosum. Limitations of their study includes the assumption that the vessels were fully constrained to the brain, the fact that using dichotomous thresholding of the vessel atlases could cause elimination of small vessels and could lead to a discontinuity of the vessels, and that the blood flow and pressure was not considered. However, their study surely adds valuable information about the vascular stiffening effect on impact-induced brain strains and could inspire further investigation of the cerebrovascular mechanical behaviours.

Stáňa Eisová


Skull thickness and neurocranial surgery

Wittner et al., 2021Bone reconstruction is a complex procedure in which multiple factors such as size, shape and location of the defect have to be considered. With time, several approaches have arisen in order to design more precise patient-specific implants. Focusing on the skull, a new study by Wittner and colleagues (2021) explores two different approaches for cranial reconstruction. The first one is based on computer-aided design (CAD) techniques, which have traditionally been used for implants design. The second one supplies morphological information of both inner and outer cranial surfaces through thin-plate splines (TPS) interpolant function. Both methods were used in order to reconstruct cranial defects of three different clinical cases and create patient-specific implants. With this purpose, CTs from 20 complete skulls were used as a reference and three of them were used to virtually recreate the damaged areas of the corresponding clinical cases based on a set of anatomical landmarks. The results of this study show a generalized high geometric accuracy for both approaches. However, TPS is more accurate in terms of thickness deviation, and therefore allows to reproduce implants with patient-specific cranial thickness distribution. This is an advantage regarding bone biomechanics and patients aesthetics, although TPS can be a more time-consuming choice as it implies previous and personalized treatment of the data for each case. For this reason, advances in computing systems such as machine learning, as suggested by the authors of this survey, could make a difference in bone reconstruction procedures in the upcoming years.

Irene del Olmo


Imaging primate brain evolution

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The primate brain stems from millions of years of evolution, and comparing the different species is a great way to study its evolutionary history. However, comparative anatomy requires large bodies of accurate quantitative data, which the brain lacks due to its fragile and complex nature. In their latest review, Friedrich et al. (2021) set their sights on neuroimaging as the solution to this problem. They explain that recent advancements in this field now allow cross-species studies of the brain using magnetic resonance imaging (MRI). The importance of MRI resides in several of its characteristics: it is a non-invasive and therefore repeatable procedure, its costs are low, and its results are easy to share amongst researchers.

In relation to brain structure, comparative neuroimaging (1) promotes interspecies comparisons through the creation of maps of homologous sulci landmarks; (2) provides more representative parcellations, which benefit allometric studies; (3) and helps test hypotheses regarding gyrification during development, since it allows for measurements at any point in time. As for brain connectivity, studying interactions between brain areas is revealing gross differences between primate species, as well as the governing principles of information processing (e.g. proximity-based interconnections and the role of certain areas as hubs to balance communication and energy costs). Finally, MRI is also useful for brain function because it can detect increased brain activity. Nevertheless, only general cognitive abilities such as brain lateralisation and integration are widely accepted as being compatible between species.

Lastly, the authors share their hopes for a fully imaged primate evolutionary tree, which would allow us to comprehend the adaptations of a specific brain to its environmental niche within the framework of its evolutionary history. There is much work to be done, but this emerging field promises the opportunity to research brain evolution across interacting species, providing a novel neuro-ecological perspective.

Tim Schuurman


Tullia

Tullia Curto 2021A new PhD project is beginning this month, carrying out our research line on the structural relationship between eyes and orbits. Tullia Curto is an ophthalmologist at the “Hospital Universitario de Burgos” (Spain), and she will investigate the spatial integration between soft and hard tissues of the orbital cavity. Through multivariate statistics and topological models, we will develop quantitative approaches to identify spatial constraints within the eye-skull functional system. As a medical doctor, she is interested in considering the possibility that such spatial constraints can influence the eyeball growth and development, with consequent effects on vision. That’s why, for this study, we will collaborate with Michael Masters.


Parietal bone size and orbit orientation in humans

In previous studies on modern human craniofacial integration, we have shown that variation in antero-posterior length of the parietal bone is associated with rotation of the anterior cranial base, and that the vertical rotation of the orbits relative to the frontal bone profile is an important source of individual variation. This week, we have published a study on the relationship between these two patterns of shape variation, as to investigate the association between parietal bone size and orbit orientation. In a CT sample of 30 adult modern humans, we merged the landmark sets from the two previous analyses, to include the parietal and frontal bone outlines, the anterior cranial base, the temporal tips, and the orbits. The main pattern of shape variation deals with enlargement of the parietal bone, extension of the cranial base, and rotation of the and orbits. Individuals with antero-posteriorly elongated vaults tend to have vertically shorter cranial bases and ventrally oriented bases and orbits. This confirms that, in adult modern humans, the orientation of the orbits changes in coordination with that of the anterior cranial base, and in association with the extension of the parietal bone. We also show that covariation between the parietal bone and the cranial base and orbits depends on their reciprocal spatial relationships, more than on shape influences. The modularity analysis points to an anterior-to-posterior partition, with stronger integration among the orbits, anterior base, and frontal bone on the one hand, and the posterior vault and cranial base on the other. The orientation of the orbits, related to the direction of gaze, certainly is a critical factor in craniofacial architecture. The seemingly complementary variation in parietal bone size and orbit-base orientation might contribute to accommodate brain and skull variability while maintaining gaze direction and head balance. Further studies should consider a three-dimensional approach, and examine the parietal-orbit relationship in an inter-specific sample, possibly considering the influence of the upper body morphology, as well as the effect of posture or locomotion.

Sofia Pedro


Skull lights

Andreas Feininger - 1951

Andreas Feininger, 1951


Inside reptile skulls

Research on brain evolution is becoming more and more interested in reptiles. The ecological diversity and complex sensory systems of snakes, for example, make them great models for investigating the link between structure and function.

Segall et al. tested whether they could link the endocranial morphology of snakes to ecological factors affecting sensory processing. They used a phylogenetically diverse sample of 36 snakes species with different aquatic habits to ensure the results reflected specific sensory adaptations to shared ecological pressures. They considered the species’ differences in foraging habitat (land or water) and activity period (diurnal, nocturnal, cathemeral), among other sensory-ecology factors. The snakes’ endocrania were reconstructed from micro-CT data and analyzed through 3D geometric morphometrics. The results showed that size drove shape variation across the first component. It distinguished between the long and narrow endocrania of large-headed snakes and the more globular ones of small-headed snakes. Shape variation along the second component reflected phylogenetic differences, mainly between the smaller snake species. Regarding the ecological traits, the authors observed that the activity period was associated with shape variation in the optic and olfactory tracts, and the foraging habitat was associated with shape changes in the cerebellum. This study shows that endocranial shape can supply valuable information in the studies of sensory adaptations of snakes; however, it cannot infer snake ecology without phylogenetic information.

Studies like this, linking structure and function, especially if using brain data, can benefit from reference brain models and atlases to identify the anatomical areas.

In the same issue of Brain Structure and Function, Hoops et al. have published an atlas of a lizard brain based on a consensus model generated from MRIs from 13 male tawny dragons (Ctenophorus decresii). Using the average of several individuals instead of a single brain increases the contrast and resolution of the atlas and helps to identify the boundaries between adjacent structures. Apart from the olfactory bulbs, the 3D atlas includes 224 brain structures segmented on the left hemisphere. This atlas is available as supplementary material and through the Open Science Framework. In the future, atlases should make use of multimodal imaging and include histological and connectivity information.

Sofia Pedro