Postnatal interaction of size and shape in the human endocranium and brain structures

Human phylogenetic history is directly related to brain evolution. But many biologic processes related to the appearance of this complex organ are unknown, mainly due to the fact that it is an organ composed of soft tissue, which is not sensitive to the fossilization processes. Hence, to infer human brain evolution it is essential to study the indirect evidences it leaves in the cranial bones, such as the endocranial size (cranial capacity) and shape. In this sense, the hominid fossil record has an important cranial representation in relation to other bones. However, in order to interpret the information the cranium provides about the brain it shelter and infer evolutive theories, it is vital to understand the relationship between the brain and the endocranial vault. In this PhD, modern human endocranium and brain growth and development will be characterized from a morphometric point of view, with the aim of defining how these two structures interact and correlate throughout maturation from birth to adulthood. This body of knowledge will be applied to enlighten our interpretations of the different indirect evidences we have about the human brain evolution. In this way, the present thesis research will not only contribute to our understanding of brain evolution in the human lineage, but it will also assist future medical research that investigate human brain and cranial growth and development trajectories. In order to answer these questions two data bases were created: one of them consisting of computed tomographic (CT) images to study bone structure maturation, and the other one consisting of magnetic resonance (MR) images to quantify ontogenetic changes in the soft brain tissue. These data bases contain individuals in a range from birth to the age of 31. The data was analysed by means of geometric morphometric techniques, which allow the statistic separation of size and shape changes throughout ontogeny, in this particular case. The results showed that the brain and endocranium present a close ontogenetic relationship from birth to the first adolescence (approximately to the age of 10 in females and 12.5 in males). From this time onwards the brain starts loosing volume (mainly gray matter due to neuronal rearrangements), and therefore, the close relationship between brain cortex and endocranial vault gradually diminishes, at the same time that the brain modifies its shape. For this reason, brain shape changes from adolescence onwards are not rejcted in endocranial regions. An important contribution was the construction of accurate and precise brain / endocranial volume (BV/ECV) ratio formulas dependent of sex, age and endocranial size, which may serve to extract better information from cranial data. A third main subject of this PhD was the study of asymmetric patterns in both brain and endocranium. In this sense, it was shown that the brain macroscopic asymmetries and the endocranial petal pattern are not the same for the different periods analysed, and they even change their trajectories through ontogeny. Hence, the adult asymmetric patterns are not the same than in the sub-adults. Finally, sexual dimorphism was investigated in both structures, and the characterization of growth and development divergences between females and males could be done through heterochonic processes. Growth and development of the brain and its surrounding bony endocranial tissue could be characterized in the human species, with the aid of 3D medical images and new geometric morphometric techniques specially developed for this study. New information about the ontogenetic relationship between these two structures was discovered, constituting an important tool that will enlighten human studies about brain evolution.

Neuregulin 1 (NRG1) is a multifunctional neurotrophin that mediates neurodevelopment and schizophrenia risk. The NRG1 gene undergoes extensive alternative splicing, and association of brain NRG1 type IV isoform expression with the schizophrenia-risk polymorphism rs6994992 is a potential mechanism of risk. Novel splice variants of NRG1-IV (NRG1-IVNV), with predicted unique signaling capabilities, have been cloned in fetal brain tissue. The authors investigated the temporal dynamics of transcription of NRG1-IVNV, compared with the major NRG1 isoforms, across human prenatal and postnatal prefrontal cortical development, and they examined the association of rs6994992 with NRG1-IVNV expression. NRG1 type I-IV and NRG1-IVNV isoforms were evaluated with quantitative real-time polymerase chain reaction in human postmortem prefrontal cortex tissue samples at 14 to 39 weeks gestation and postnatal ages 0-83 years. The association of rs6994992 genotype with NRG1-IVNV expression and the subcellular distribution and proteolytic processing of NRG1-IVNV isoforms were also determined. Expression of NRG1 types I, II, and III was temporally regulated during prenatal and postnatal neocortical development. NRG1-IVNV was expressed from 16 weeks gestation until age 3. Homozygosity for the schizophrenia risk allele (T) of rs6994992 conferred lower cortical NRG1-IVNV levels. Assays showed that NRG1-IVNV is a novel nuclear-enriched, truncated NRG1 protein resistant to proteolytic processing. To the authors' knowledge, this study provides the first quantitative map of NRG1 isoform expression during human neocortical development and aging. It identifies a potential mechanism of early developmental risk for schizophrenia at the NRG1 locus, involving a novel class of NRG1 proteins.

Establishing dependencies and connectivity among different structures in the human brain is an extremely complex issue. Methods that are often used for connectivity analysis are based on correlation mechanisms. Correlation methods can analyze changes in signal shape or instantaneous power level. Although recent studies imply that observation of results from both groups of methods together can disclose some of the basic functions and behavior of the human brain during mental activity and decision-making, there is no technique covering changes in the shape of signals along with changes in their power levels. We present a method using a time evaluation of the correlation along with a comparison of power levels in every available contact pair from intracranial electrodes placed in deep brain structures. Observing shape changes in signals after stimulation together with their power levels provides us with new information about signal character between different structures in the brain during task-related events - visual stimulation with motor response. The results for a subject with 95 intracerebral contacts used in this paper demonstrate a clear methodology capable of spatially analyzing connectivity among deep brain structures.

Sizing up the soul’s seat

Birds exhibit a huge array of behavior, ecology and physiology, and occupy nearly every environment on earth, ranging from the desert outback of Australia to the tropical rain forests of Panama. Some birds have adopted a fully nocturnal lifestyle, such as the barn owl and kiwi, while others, such as the albatross, spend nearly their entire life flying over the ocean. Each species has evolved unique adaptations over millions of years to function in their respective niche. In order to increase processing power or network efficiency, many of these adaptations require enlargements and/or specializations of the brain as a whole or of specific brain regions. In this study, we examine the relative size and morphology of 9 telencephalic regions in a number of Paleognath and Neognath birds and relate the findings to differences in behavior and sensory ecology. We pay particular attention to those species that have undergone a relative enlargement of the telencephalon to determine whether this relative increase in telencephalic size is homogeneous across different brain regions or whether particular regions have become differentially enlarged. The analysis indicates that changes in the relative size of telencephalic regions are not homogeneous, with every species showing hypertrophy or hypotrophy of at least one of them. The three-dimensional structure of these regions in different species was also variable, in particular that of the mesopallium in kiwi. The findings from this study provide further evidence that the changes in relative brain size in birds reflect a process of mosaic evolution.

Morphometric Analysis of Mandibular Growth in Skeletal Class III Malocclusion

In terrestrial pulmonate gastropods Cochlodina laminata, Monachoides incarnata, Helicigona lapicida, Arianta arbustorum, Cepaea hortensis, Trochulus hispidus and Succinea putris, the morphological properties of the pupil of camera-like eyes were studied for the first time: location, spatial orientation, change in spatial orientation, structure, shape, shape change, relative size, change in relative size. Several methods were used in the work: making of preparations of isolated eyes, making of histological preparations of eyes, light microscopy, morphometric analysis, statistical analysis, calculations. All the studied morphological properties of the pupil of the camera-like eyes of C. laminata, M. incarnata, H. lapicida, A. arbustorum, C. hortensis and T. hispidus are similar to the analogous morphological properties of the pupil of the camera-like eyes of other species of terrestrial pulmonates. One of the studied morphological properties of the pupil of the camera-like eye of S. putris – the relative size – differs from the analogous morphological property of the pupil of the camera-like eyes of other species of terrestrial pulmonates.

By comparing species-specific developmental patterns, we can approach the question of how development shapes adult morphology and contributes to the evolution of novel forms. Studies of evolutionary changes to brain development in primates can provide important clues about the emergence of human cognition, but are hindered by the lack of preserved neural tissue in the fossil record. As a proxy, we study the shape of endocasts, virtual imprints of the endocranial cavity, using 3D geometric morphometrics. We have previously demonstrated that the pattern of endocranial shape development is shared by modern humans, chimpanzees and Neanderthals after the first year of life until adulthood. However, whether this represents a common hominoid mode of development is unknown. Here, we present the first characterization and comparison of ontogenetic endocranial shape changes in a cross-sectional sample of modern humans, chimpanzees, gorillas, orangutans and gibbons. Using developmental simulations, we demonstrate that from late infancy to adulthood ontogenetic trajectories are similar among all hominoid species, but differ in the amount of shape change. Furthermore, we show that during early ontogeny gorillas undergo more pronounced shape changes along this shared trajectory than do chimpanzees, indicative of a dissociation of size and shape change. As shape differences between species are apparent in even our youngest samples, our results indicate that the ontogenetic trajectories of extant hominoids diverged at an earlier stage of ontogeny but subsequently converge following the eruption of the deciduous dentition.

Overview The seismic method utilizes the propagation of waves through the earth. To introduce the basic concepts of wave motion, we first discuss waves on a stretched string (§2.1.1) and introduce definitions of phase, frequency, wavelength, and other terms dealing with periodicity. Because wave propagation depends upon the elastic properties of the rocks, we next discuss some of the basic concepts of elasticity. (For more thorough treatments, see Saada, 1974, or Landau and Lifshitz, 1986.) The size and shape of a solid body can be changed by applying forces to the external surface of the body. These external forces are opposed by internal forces, which resist the changes in size and shape. As a result, the body tends to return to its original condition when the external forces are removed. Similarly, a fluid resists changes in size (volume) but not changes in shape. This property of resisting changes in size or shape and of returning to the undeformed condition when the external forces are removed is called elasticity . A perfectly elastic body is one that recovers completely after being deformed. Many substances including rocks can be considered perfectly elastic without appreciable error provided the deformations are small, as they are in seismic surveys. The theory of elasticity relates the forces that are applied to the external surface of a body to the resulting changes in size and shape. The relations between the applied forces and the deformations are most conveniently expressed in terms of the concepts of stress and strain.

IntroductionRegional changes in brain stiffness were previously demonstrated in an experimental obstructive hydrocephalus juvenile rat model. The open cranial sutures in the juvenile rats have influenced brain compression and mechanical properties during hydrocephalus development and the extent by which closed cranial sutures in adult hydrocephalic rat models affect brain stiffness in-vivo remains unclear. The aims of this study were to determine changes in brain tissue mechanical properties and brain structure size during hydrocephalus development in adult rat with fixed cranial volume and how these changes were related to brain tissue deformation.MethodsHydrocephalus was induced in 9 female ten weeks old Sprague-Dawley rats by injecting 60 μL of a kaolin suspension (25%) into the cisterna magna under anaesthesia. 6 sham-injected age-matched female SD rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before and then at 3 days post injection. T2-weighted anatomical MR images were collected to quantify ventricle and brain tissue cross-sectional areas. MR elastography (800 Hz) was used to measure the brain stiffness (G*, shear modulus).ResultsBrain tissue in the adult hydrocephalic rats was more compressed than the juvenile hydrocephalic rats because the skulls of the adult hydrocephalic rats were unable to expand like the juvenile rats. In the adult hydrocephalic rats, the cortical gray matter thickness and the caudate-putamen cross-sectional area decreased (Spearman, P < 0.001 for both) but there were no significant changes in cranial cross-sectional area (Spearman, P = 0.35), cortical gray matter stiffness (Spearman, P = 0.24) and caudate-putamen (Spearman, P = 0.11) stiffness. No significant changes in the size of brain structures were observed in the controls.ConclusionsThis study showed that although brain tissue in the adult hydrocephalic rats was severely compressed, their brain tissue stiffness did not change significantly. These results are in contrast with our previous findings in juvenile hydrocephalic rats which had significantly less brain compression (as the brain circumference was able to stretch with the cranium due to the open skull sutures) and had a significant increase in caudate putamen stiffness. These results suggest that change in brain mechanical properties in hydrocephalus is complex and is not solely dependent on brain tissue deformation. Further studies on the interactions between brain tissue stiffness, deformation, tissue oedema and neural damage are necessary before MRE can be used as a tool to track changes in brain biomechanics in hydrocephalus.

The brain is a highly plastic organ and is shaped not only during prenatal but also during postnatal development. The analysis and comparison of ontogenetic patterns of endocranial size increase and endocranial shape changes can therefore add further evidence for the interpretation of hominin brain evolution. Here we focus on digital endocast data and the methodology used to document and compare developmental patterns of endocranial shape changes. We outline how geometric morphometrics of endocranial landmark data can be used in an evo-devo approach to human brain evolution, discuss how developmental simulations help to compare ontogenetic patterns among species, present different visualization techniques that help to interpret ontogenetic shape changes, provide an overview of our current knowledge, present new data on early postnatal shape changes in apes, and discuss open questions.

Patterns of change in mandibular and facial shape associated with the use of forces to retract the maxilla

Ribbon synapses differ from conventional chemical synapses in that they contain, within the cloud of synaptic vesicles (SV's), a specialized synaptic body, most often termed synaptic ribbon (SR). This body assumes various forms. Reconstructions reveal that what appear as rod- or ribbon-like profiles in sections are in fact rectangular or horseshoe-shaped plates. Moreover, spherical, T-shaped, table-shaped, and highly pleomorphic bodies may be present. In mammals, ribbon synapses are present in afferent synapses of photoreceptors, bipolar nerve cells, and hair cells of both the organ of Corti and the vestibular organ. Synaptic ribbons (SR's) are also found in the intrinsic cells of the third eye, the pineal gland, and in the lateral line system. The precise function of SR's is enigmatic. The prevailing concept is that SR's function as conveyor belts to channel SV's to the presynaptic membrane for neurotransmitter release by means of exocytosis. The present article reviews the evidence that speaks for a plasticity of these organelles in the retina and the third eye, as reflected in changes in number, size, shape, location, and grouping pattern. SR plasticity is especially pronounced in the mammalian and submammalian pineal gland and in cones and bipolar cells of teleost fishes. Here, SR number and size wax and wane according to the environmental lighting conditions. In the pineal SR numbers increase at night and decrease during the day. In teleost cones, SR's are in their prime during daytime and decrease or disappear at night, when transmitter release is enhanced. In addition to numerical changes, SR's may also exhibit changes in size, shape, grouping pattern, and location. In the mammalian retina of adults, in contrast to the developing retina, the reported signs of SR plasticity are subtle and not always consistent. They may reflect changes in function or may represent signs of degradation. To distinguish between the-two, more detailed studies under selected experimental conditions are required. Probably the strongest evidence for SR plasticity in the mammalian retina is that in hibernating squirrels SR's leave the synaptic site and accumulate in areas as far as 5 microns from the synapse. Changes in shape include the occurrence of club-shaped SR's and round SR's or synaptic spheres (SS's). SS's may represent a special type of synaptic body, yet belonging to the family of SR's, or may be related to the catabolism of SR's. SR number is regulated by Ca2+ in teleost cones, whereas in the mammalian pineal gland cGMP is involved. An interesting biochemical feature of ribbon synapses is that they lack synapsins. The presently reviewed results suggest to us that SR's do not primarily function as conveyor belts, but are devices to immobilize SV's in inactive ribbon synapses.

Throughout hominin evolution, the brain of our ancestors underwent a 3-fold increase in size and substantial structural reorganization. However, inferring brain reorganization from fossil hominin neurocrania (=braincases) remains a challenge, above all because comparative data relating brain to neurocranial structures in living humans and great apes are still scarce. Here we use MRI and same-subject spatially aligned computed tomography (CT) and MRI data of humans and chimpanzees to quantify the spatial relationships between these structures, both within and across species. Results indicate that evolutionary changes in brain and neurocranial structures are largely independent of each other. The brains of humans compared to chimpanzees exhibit a characteristic posterior shift of the inferior pre- and postcentral gyri, indicative of reorganization of the frontal opercular region. Changes in human neurocranial structure do not reflect cortical reorganization. Rather, they reflect constraints related to increased encephalization and obligate bipedalism, resulting in relative enlargement of the parietal bones and anterior displacement of the cerebellar fossa. This implies that the relative position and size of neurocranial bones, as well as overall endocranial shape (e.g., globularity), should not be used to make inferences about evolutionary changes in the relative size or reorganization of adjacent cortical regions of fossil hominins.

Closure in geochemical data serves to complicate interpretation because it adds variation un-related to geochemical processes. Geoscientists have used three methods to avoid closure: the Theorem of Geochemical Material Transfer, Molar Element Ratio Analysis, and Compositional Data Analysis. Whereas each has its advantages, in many scenarios, mathematically induced closure effects are modest and/or overwhelmed by the effects of material transfer, preventing closure from impairing conclusions derived using geochemical data analysis. This paper derives an equation from the definition of a concentration illustrating that the relative concentration change is a function of the relative change in the amount of the element (material transfer) and the relative change in the size of the rock (closure): dx/x = dX/X – dS/S , where x is component concentration, X is the amount of that component in a rock, and S is the size of the rock. Functional analysis of this equation identifies two scenarios where closure does not add significant variance or distortion to concentration data: (i) in perfect exchange processes (when the system size doesn't change, so closure effects are absent; dS = 0 ), and (ii) when the relative amount of material transfer is larger than the relative change in system size ( dX/X &gt;&gt; dS/S ). This latter scenario occurs when X is small (the concentration is at minor/trace levels), or when dX is large (the amount of material transfer is large relative to S ). In each scenario, the effect of material transfer ( dX/X ) is larger than that of closure ( dS/S ), making geochemical data easy to interpret.