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Structural connections between cortical areas form an intricate network with a high degree of specificity. Many aspects of this complex network organization in the adult mammalian cortex are captured by an architectonic type principle, which relates structural connections to the architectonic differentiation of brain regions. In particular, the laminar patterns of projection origins are a prominent feature of structural connections that varies in a graded manner with the relative architectonic differentiation of connected areas in the adult brain. Here we show that the architectonic type principle is already apparent for the laminar origins of cortico-cortical projections in the immature cortex of the macaque monkey. We find that prenatal and neonatal laminar patterns correlate with cortical architectonic differentiation, and that the relation of laminar patterns to architectonic differences between connected areas is not substantially altered by the complete loss of visual input. Moreover, we find that the degree of change in laminar patterns that projections undergo during development varies in proportion to the relative architectonic differentiation of the connected areas. Hence, it appears that initial biases in laminar projection patterns become progressively strengthened by later developmental processes. These findings suggest that early neurogenetic processes during the formation of the brain are sufficient to establish the characteristic laminar projection patterns. This conclusion is in line with previously suggested mechanistic explanations underlying the emergence of the architectonic type principle and provides further constraints for exploring the fundamental factors that shape structural connectivity in the mammalian brain. Supplementary Information The online version contains supplementary material available at 10.1007/s00429-021-02219-6.

Mesoscopic (0.1-0.5 mm) interrogation of the living human brain is critical for a comprehensive understanding of brain structure and function. However, in vivo techniques for mesoscopic imaging have been hampered by the sensitivity challenges of acquiring data at very high resolutions and the lack of analysis tools that can retain fine-scale detail while also accurately positioning measurements relative to the complex folded structure of the cerebral cortex. Here, we present an experimental dataset in which we image the anatomical structure of the visual and auditory cortices of five participants at 0.35 × 0.35 × 0.35 mm3 resolution. To analyze this challenging dataset, we design and implement two sets of novel methodology: a method for mitigating imaging artifacts related to blood motion and a suite of software tools for accurate quantification and visualization of the mesoscopic structure of the cortical surface. Applying these methods, we demonstrate the ability to clearly identify structures that are visible only at the mesoscopic scale, including cortical layers and intracortical blood vessels. We freely share our dataset and tools with the research community, thereby enabling investigations of fine-scale neurobiological structures in both the current and future datasets. Overall, our results demonstrate the viability of mesoscopic imaging as a quantitative tool for studying the living human brain.

Uncovering organizational principles of the cerebral cortex is essential for proper understanding of this prominent structure of the mammalian brain. The theory of the dual origin of the cerebral cortex offers such organizational principle. Here, we demonstrate that a duality pertains to the connectional architecture of the cerebral cortex of different mammals. This dual structure also constitutes a major axis of organization of the transcriptional architecture of the cortex and reflects the expression of different morphogens stemming from distinct patterning centers in the developing pallium. The duality of the cortex is also reflected in its spatial dimension, highlighting cortical areas as spatially ordered constellations that are centered around the paleocortex and archicortex, with the later primordial moieties reminiscent of antipodal points in the cortical sheet. The ontogeny of the uncovered dual connectional structure might be rooted in heterochronous neurodevelopmental gradients in the developing pallium, a suggestion corroborated by computational modeling. In all, the current results exemplify the duality of the cerebral cortex as an overarching organizational principle, reflected across the different levels of cortical architecture of different mammalian species, defining a natural axis of mammalian cortical organization.

Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by silencing of the FMR1 gene and subsequent loss of its protein product, fragile X retardation protein (FMRP). One of the most robust neuropathological findings in post-mortem human FXS and Fmr1 KO mice is the abnormal increase in dendritic spine densities, with the majority of spines showing an elongated immature morphology. However, the exact mechanisms of how FMRP can regulate dendritic spine development are still unclear. Abnormal dendritic spines can result from disturbances of multiple factors during neurodevelopment, such as alterations in neuron numbers, position and glial cells. In this study, we undertook a comprehensive histological analysis of the cerebral cortex in Fmr1 KO mice. They displayed significantly fewer neuron and PV-interneuron numbers, along with altered cortical lamination patterns. In terms of glial cells, Fmr1 KO mice exhibited an increase in Olig2-oligodendrocytes, which corresponded to the abnormally higher myelin expression in the corpus callosum. Iba1-microglia were significantly reduced but GFAP-astrocyte numbers and intensity were elevated. Using primary astrocytes derived from KO mice, we further demonstrated the presence of astrogliosis characterized by an increase in GFAP expression and astrocyte hypertrophy. Our findings provide important information on the cortical architecture of Fmr1 KO mice, and insights towards possible mechanisms associated with FXS. Electronic supplementary material The online version of this article (10.1186/s13041-019-0478-8) contains supplementary material, which is available to authorized users.

Application of RNA sequencing has enabled the characterization of genome-wide gene expression in the human brain, including distinct layers of the neocortex. Neuroanatomically, the molecular patterns that underlie the laminar organization of the neocortex can help link structure to circuitry and function. To advance our understanding of cortical architecture, we created LaminaRGeneVis, a web application that displays across-layer cortical gene expression from multiple datasets. These datasets were collected using bulk, single-nucleus, and spatial RNA sequencing methodologies and these data were harmonized to facilitate comparisons between datasets. The online resource facilitates single- and multi-gene analyses by providing figures and statistics for user-friendly assessment of laminar gene expression patterns in the adult human neocortex.Availability and implementationLaminaRGeneVis is available at https://ethanhkim.shinyapps.io/laminargenevis. The source code and data is accessible at https://github.com/ethanhkim/laminargenevis.

Background Tributyltin, a well-known endocrine disruptor, is widely used in agriculture and industry. Previous studies have shown that tributyltin could cause deleterious effects on bone health by impairing the adipo-osteogenic balance in bone marrow. Methods To investigate further the effects of tributyltin on bone, weaned male SD rats were treated with tributyltin (0.5, 5 or 50 μg·kg− 1) or corn oil by gavage once every 3 days for 60 days in this study. Then, we analyzed the effects of tributyltin on geometry, the polar moment of inertia, mineral content, relative abundances of mRNA from representative genes related to adipogenesis and osteogenesis, serum calcium ion and inorganic phosphate levels. Results Micro-computed tomography analysis revealed that treatment with 50 μg·kg− 1 tributyltin caused an obvious decrease in femoral cortical cross sectional area, marrow area, periosteal circumference and derived polar moment of inertia in rats. However, other test results showed that exposure to tributyltin resulted in no significant changes in the expression of genes detected, femoral cancellous architecture, ash content, as well as serum calcium ion and inorganic phosphate levels. Conclusions Exposure to a low dose of tributyltin from the prepubertal to adult stage produced adverse effects on skeletal architecture and strength.

Background Cerebral arteriovenous malformations (AVMs) are rare, with incidence of 1.12-1.42 cases per 100,000 person-years(1). Few studies report applications of awake surgery. The goal of this report was to assess the interest of awake surgery in complete resection of cortical AVMs located close to eloquent speech areas, enabling detection of real functional cortical reorganization due to the AVM and parenchymal hematoma. Case report A 38-year-old right-handed patient was admitted to the University Hospital of Besancon for dysphasia due to a ruptured left temporal arteriovenous malformation. The patient underwent asleep-awake-asleep surgery. Intraoperative cortical mapping revealed the presence of functional language areas in uncommon locations compared to known neuro-functional anatomy. Discussion In this patient, speech areas were redistributed, probably due to neuroplasticity after cerebral hemorrhage, leading to a new cortical architecture, which would have been unrecognized based on preoperative radiological imaging alone. Conclusion We report the interest of awake surgery to achieve complete safe resection of ruptured AVMs located close to eloquent speech areas, using intraoperative cortical mapping.

Brain cerebral cortical architecture encoding regionally differential dendritic arborization and synaptic formation at birth underlies human behavior emergence at 2 years of age. Brain changes in 0-2 years are most dynamic across lifespan. Effective prediction of future behavior with brain microstructure at birth will reveal structural basis of behavioral emergence in typical development, and identify biomarkers for early detection and tailored intervention in atypical development. Here, we aimed to evaluate the neonate whole-brain cortical microstructure quantified by diffusion MRI for predicting future behavior. We found that individual cognitive and language functions assessed at age of 2 years were robustly predicted by neonate cortical microstructure using support vector regression. Remarkably, cortical regions contributing heavily to the prediction models exhibited distinctive functional selectivity for cognition and language. These findings highlight regional cortical microstructure at birth as potential sensitive biomarker in predicting future neurodevelopmental outcomes and identifying individual risks of brain disorders.

At the earliest developmental stages, spontaneous activity synchronizes local and large-scale cortical networks. These networks form the functional template for the establishment of global thalamocortical networks and cortical architecture. The earliest connections are established autonomously. However, activity from the sensory periphery reshapes these circuits as soon as afferents reach the cortex. The early-generated, largely transient neurons of the subplate play a key role in integrating spontaneous and sensory-driven activity. Early pathological conditions—such as hypoxia, inflammation, or exposure to pharmacological compounds—alter spontaneous activity patterns, which subsequently induce disturbances in cortical network activity. This cortical dysfunction may lead to local and global miswiring and, at later stages, can be associated with neurological and psychiatric conditions.

Cortical single neuron activity and local field potential patterns change at different depths of general anesthesia. Here, we investigate the associated network level changes of functional connectivity. We recorded ongoing electrocorticographic (ECoG) activity from temporo-parieto-occipital cortex of 6 ferrets at various levels of isoflurane/nitrous oxide anesthesia and determined functional connectivity by computing amplitude envelope correlations. Through hierarchical clustering, we derived typical connectivity patterns corresponding to light, intermediate and deep anesthesia. Generally, amplitude correlation strength increased strongly with depth of anesthesia across all cortical areas and frequency bands. This was accompanied, at the deepest level, by the emergence of burst-suppression activity in the ECoG signal and a change of the spectrum of the amplitude envelope. Normalization of functional connectivity to the distribution of correlation coefficients showed that the topographical patterns remained similar across depths of anesthesia, reflecting the functional association of the underlying cortical areas. Thus, while strength and temporal properties of amplitude co-modulation vary depending on the activity of local neural circuits, their network-level interaction pattern is presumably most strongly determined by the underlying structural connectivity.

In the perinatal brain, regional cortical architecture and connectivity lay the foundations for functional circuits and emerging behaviour. Interruptions or atypical development during or before this period may therefore have long-lasting consequences. However, to be able to investigate these deviations, we need a measure of how this architecture evolves in the typically developing brain. To this end, in a large cohort of 241 term-born infants we used Magnetic Resonance Imaging to estimate cortical profiles based on morphometry and microstructure over the perinatal period (37-44 weeks post-menstrual age, PMA). Using the covariance of these profiles as a measure of inter-areal network similarity (Morphometric Similarity Networks; MSN), we clustered these networks into distinct modules. The resulting modules were consistent and symmetric, and corresponded to known functional distinctions, including sensory-motor, limbic and association regions and were spatially mapped onto known cytoarchitectonic tissue classes. Posterior (parietal, occipital) regions became more morphometrically similar with increasing PMA, while peri-cingulate and medial temporal regions became more dissimilar. Network strength was associated with PMA: Within-network similarity increased over PMA suggesting emerging network distinction. These changes in cortical network architecture over an eight-week period are consistent with, and likely underpin, the highly dynamic behavioural and cognitive development occurring during this critical period. The resulting cortical profiles might provide normative reference to investigate atypical early brain development.

Highlights • Neural correlates of clinical outcomes in pediatric PTSD are poorly understood. • Remission and persistence show unique patterns of cortical development over time. • Nonremitters exhibit atypical decreases in prefrontal, parietal, and occipital CSA. • PTSD remission was associated with cortical expansion in the prefrontal cortex., Background Previous studies have identified structural brain abnormalities in pediatric PTSD. However, little is known about what structural brain substrates may confer recovery versus persistence of PTSD in the context of the developing brain. Methods This naturalistic longitudinal study used T1-weighted MRI to evaluate cortical thickness and surface area in youth with a PTSD diagnosis (n = 28) and typically developing healthy youth (TD; n = 27) at baseline and one-year follow-up. Of the PTSD group, 10 youth were remitters at one-year follow up while 18 had persistent PTSD. Whole-brain estimates of cortical thickness and surface area were extracted to identify differences in cortical architecture associated with PTSD remission and persistence as compared to typical development. Results Youth who achieved PTSD remission entered the study with significantly lower trauma exposure and reduced symptom severity as compared to nonremitters. PTSD persistence was associated with decreased surface area over time in the ventrolateral prefrontal cortex (vlPFC) as compared to both remitters and TD youth. In contrast, PTSD remission was associated with expansion of frontal pole surface area and ventromedial PFC (vmPFC) thickness over time. Across clinical groups, vmPFC thickness was further inversely associated with symptom severity. Conclusions To our knowledge, these findings represent the first report of cortical substrates underlying persistence versus remission in pediatric PTSD. Together, these findings suggest active structural developmental processes unique to both remission and nonremission in youth with PTSD. In particular, expansion of prefrontal regions implicated in emotion regulation may facilitate recovery from PTSD in youth and would warrant further study.

Two identical autonomous dynamical systems unidirectionally coupled in a sender-receiver configuration can exhibit anticipated synchronization (AS) if the Receiver neuron (R) also receives a delayed negative self-feedback. Recently, AS was shown to occur in a three-neuron motif with standard chemical synapses where the delayed inhibition was provided by an interneuron. Here we show that a two-neuron model in the presence of an inhibitory autapse, which is a massive self-innervation present in the cortical architecture, may present AS. The GABAergic autapse regulates the internal dynamics of the Receiver neuron and acts as the negative delayed self-feedback required by dynamical systems in order to exhibit AS. In this biologically plausible scenario, a smooth transition from the usual delayed synchronization (DS) to AS typically occurs when the inhibitory conductance is increased. The phenomenon is shown to be robust when model parameters are varied within a physiological range. For extremely large values of the inhibitory autapse the system undergoes to a phase-drift regime in which the Receiver is faster than the Sender. Furthermore, we show that the inhibitory autapse promotes a faster internal dynamics of the free-running Receiver when the two neurons are uncoupled, which could be the mechanism underlying anticipated synchronization and the DS-AS transition., 6 pages, 6 figures

Micro-slit-beam radiation therapy (MRT) using synchrotron-generated X-ray beams allows for extremely high-dose irradiation. However, the toxicity of MRT in central nervous system (CNS) use is still unknown. To gather baseline toxicological data, we evaluated mortality in normal mice following CNS-targeted MRT. Male C57BL/6 J mice were head-fixed in a stereotaxic frame. Synchrotron X-ray-beam radiation was provided by the SPring-8 BL28B2 beam-line. For MRT, radiation was delivered to groups of mice in a 10 × 12 mm unidirectional array consisting of 25-μm-wide beams spaced 100, 200 or 300 μm apart; another group of mice received the equivalent broad-beam radiation therapy (BRT) for comparison. Peak and valley dose rates of the MRT were 120 and 0.7 Gy/s, respectively. Delivered doses were 96–960 Gy for MRT, and 24–120 Gy for BRT. Mortality was monitored for 90 days post-irradiation. Brain tissue was stained using hematoxylin and eosin to evaluate neural structure. Demyelination was evaluated by Klüver–Barrera staining. The LD50 and LD100 when using MRT were 600 Gy and 720 Gy, respectively, and when using BRT they were 80 Gy and 96 Gy, respectively. In MRT, mortality decreased as the center-to-center beam spacing increased from 100 μm to 300 μm. Cortical architecture was well preserved in MRT, whereas BRT induced various degrees of cerebral hemorrhage and demyelination. MRT was able to deliver extremely high doses of radiation, while still minimizing neuronal death. The valley doses, influenced by beam spacing and irradiated dose, could represent important survival factors for MRT.

Brain regions of the cerebral cortex differ in their cytoarchitecture as well as in the intrinsic connectivity within an area and the organization of macroscopic connections between different cortical areas. Nonetheless, it is not clear which rules underlie the relationship of cellular and fiber architecture, and how the characteristic cortical micro- and macro-connectivity are related to each other. In order to identify principles of cortical connectivity, we systematically investigate various parameters of cortical architecture and their relation to the organization of anatomical connections among cortical areas. Characteristic parameters of cortical architecture include the differential density and distribution of neurons and neuron types across the layers of cortical areas, as well as the regional distribution of different receptors of neurotransmitter systems. The cytoarchitectonic characterization of the brain is a classic approach of neuroanatomy, which recently has been supplemented by new techniques for labeling specific neural components as well as novel optical and analytical approaches. However, the systematic quantitative acquisition of architectonic and morphological parameters of the human brain has only just begun. It is a fundamental challenge to gather and quantify the extremely extensive and detailed histological data (“big data”) by novel image processing techniques. This challenge is taken up in the BigBrain project. Extensive anatomical data already exist for a number of animal models, for example, the brains of nonhuman primates, the cat or the mouse. However, for each single parameter it has to be demonstrated how far these data can be generalized across species. Previous analyses support the notion that the regionally specific cytoarchitecture of the cerebral cortex is closely linked to the existence and the laminar projection patterns of cortico-cortical connections. These results imply systematic relationships between the patterns of macroscopic connections among cortical areas and the regionally specific intrinsic circuitry within cortical areas. Such relations are the basis of generic models of multiscale cortical connectivity, which reflect essential anatomical and functional properties of mammalian cortical organization.

The perceptual brain is designed around multisensory input. Areas once thought dedicated to a single sense are now known to work with multiple senses. It has been argued that the multisensory nature of the brain reflects a cortical architecture for which task, rather than sensory system, is the primary design principle. This supramodal thesis is supported by recent research on human echolocation and multisensory speech perception. In this review, we discuss the behavioural implications of a supramodal architecture, especially as they pertain to auditory perception. We suggest that the architecture implies a degree of perceptual parity between the senses and that cross-sensory integration occurs early and completely. We also argue that a supramodal architecture implies that perceptual experience can be shared across modalities and that this sharing should occur even without bimodal experience. We finish by briefly suggesting areas of future research.

Treadmill running and tibial loading are two common modalities used to assess the role of mechanical stimulation on the skeleton preclinically. The primary advantage of treadmill running is its physiological relevance. However, the applied load is complex and multiaxial, with observed results influenced by cardiovascular and musculoskeletal effects. In contrast, with tibial loading, a direct uniaxial load is applied to a single bone, providing the advantage of greater control but with less physiological relevance. Despite the importance and wide-spread use of both modalities, direct comparisons are lacking. In this study, we compared effects of targeted tibial loading, treadmill running, and their combination on cancellous and cortical architecture in a murine model. We show that tibial loading and treadmill running differentially improve bone mass, with tibial loading resulting in thicker trabeculae and increased cortical mass, and exercise resulting in greater number of trabeculae and no cortical mass-based effects. Combination of the modalities resulted in an additive response. These data suggest that tibial loading and exercise may improve mass differentially., Highlights • Tibial loading increased trabecular thickness while exercise increased number. • Combined effects of loading and exercise were additive in cancellous bone. • In cortical bone, loading increased cross-sectional area. • No mass-based effects were noted due to exercise.

The architectonic type principle relates patterns of cortico-cortical connectivity to the relative architectonic differentiation of cortical regions. One mechanism through which the observed close relation between cortical architecture and connectivity may be established is the joint development of cortical areas and their connections in developmental time windows. Here, we describe a theoretical exploration of the possible mechanistic underpinnings of the architectonic type principle, by performing systematic computational simulations of cortical development. The main component of our in silico model was a developing two-dimensional cortical sheet, which was gradually populated by neurons that formed cortico-cortical connections. To assess different explanatory mechanisms, we varied the spatiotemporal trajectory of the simulated neurogenesis. By keeping the rules governing axon outgrowth and connection formation constant across all variants of simulated development, we were able to create model variants which differed exclusively by the specifics of when and where neurons were generated. Thus, all differences in the resulting connectivity were due to the variations in spatiotemporal growth trajectories. Our results demonstrated that a prescribed targeting of interareal connection sites was not necessary for obtaining a realistic replication of the experimentally observed relation between connection patterns and architectonic differentiation. Instead, we found that spatiotemporal interactions within the forming cortical sheet were sufficient if a small number of empirically well-grounded assumptions were met, namely planar, expansive growth of the cortical sheet around two points of origin as neurogenesis progressed, stronger architectonic differentiation of cortical areas for later neurogenetic time windows, and stochastic connection formation. Thus, our study highlights a potential mechanism of how relative architectonic differentiation and cortical connectivity become linked during development. We successfully predicted connectivity in two species, cat and macaque, from simulated cortico-cortical connection networks, which further underscored the general applicability of mechanisms through which the architectonic type principle can explain cortical connectivity in terms of the relative architectonic differentiation of cortical regions., Author summary The mechanisms that govern the establishment of cortico-cortical connections during the development of the mammalian brain are poorly understood. In computational simulation experiments reported here, we explored the foundations of an architectonic type principle, which attributes adult cortical connectivity to the differences in architectonic differentiation between cortical areas. Architectonic differentiation refers, among other characteristics, to the cellular composition of cortical areas. This architectonic type principle has been found to account for diverse properties of cortical connectivity across mammalian species. Our in silico model generated connectivity patterns that were consistent with the architectonic type principle, as they are typically observed in mammalian cortices, if model settings were chosen such that they corresponded to empirical observations of cortical development. Our computational experiments systematically evaluated previously proposed mechanisms of cortical development and showed that connectivity consistent with the architectonic type principle arose only from realistic assumptions about the growth of the cortical sheet.

Calcium sulfate (CS) combines remarkable properties of biodegradability, biocompatibility, and osteoconductivity but its low strength limits the range of its applications in orthopaedic surgery. In this study we have addressed this limitation by optimizing the fabrication process for pure CS, and by using mechanical testing procedures which are relevant for load carrying, or structural bone grafts (flexural tests in hydrated condition). By optimizing the processing parameters (pressure during setting, CS powder to water ratio, saturated solution) we produced CS samples with the highest flexural strength ever reported in hydrated conditions. Once these optimal conditions are used, the addition of "reinforcing" inclusions in the material decreased its strength because these inclusions actually act as defects instead of reinforcements. In addition, the CS can be formed in precise shapes while maintaining optimal processing conditions and provided a strength similar to that of bone with the same dimensions. Dense and porous materials can be combined to duplicate the trabecular and cortical architecture of long bones, with only a small loss of overall strength.

This review provides an overview on the development of the rodent whisker-to-barrel cortex system from late embryonic stage to the end of the first postnatal month. During this period the system shows a remarkable transition from a mostly genetic-molecular driven generation of crude connectivity, providing the template for activity-dependent structural and functional maturation and plasticity, to the manifestation of a complex behavioral repertoire including social interactions. Spontaneous and sensory-evoked activity is present in neonatal barrel cortex and control the generation of the cortical architecture. Half a century after its first description by Woolsey and van der Loos the whisker-to-barrel cortex system with its unique and clear topographic organization still offers the exceptional opportunity to study sensory processing and complex behavior.

For decades, it has been largely unknown to what extent multiple functional networks spatially overlap/interact with each other and jointly realize the total cortical function. Here, by developing novel sparse representation of whole-brain fMRI signals and by using the recently publicly released large-scale Human Connectome Project high-quality fMRI data, we show that a number of reproducible and robust functional networks, including both task-evoked and resting state networks, are simultaneously distributed in distant neuroanatomic areas and substantially spatially overlapping with each other, thus forming an initial collection of holistic atlases of functional networks and interactions (HAFNIs). More interestingly, the HAFNIs revealed two distinct patterns of highly overlapped regions and highly specialized regions and exhibited that these two patterns of areas are reciprocally localized, revealing a novel organizational principle of cortical function.

The objective of this thesis is to develop mathematical models of visual perception based on cortical architectures and to apply them to reproduce phenomenological experiments and to process natural images. We primarly focus on low level vision tasks and in particular we are interested in the problem of grouping and of individuation of perceptual units. In this setting we will face the problem of the reconstruction of illusory figures and the detection of retinal vessels in optical images. Then we consider the problem of encoding and decoding of the fMRI signal from in vivo acquired brain activity of visual cortex. This allows to estimate the structure of the cortex of a specific human patient and eventually to reconstruct the visual stimulus from fMRI activity, in a so called “brain reading” strategy. The difference between our approach and the state of the art literature consists in using previously defined neuromathematical models of the cortices as a-priori knowledge to regularise in vivo estimated structure. Even if it is a long term objective, we propose a first approach to improve the results in this field. The entire work of this thesis has been developed taking into account results from phenomenology of perception and results of neurophysiology.In the field of the phenomenology of perception, at the beginning of the last century, the theory of the Gestalt psychology [Wertheimer, 1938, Kohler, 1947, Kofka, 1935] defined the integration of contours and in particular they defined grouping laws underlying perception. These are crucial in the construction of visual objects: points with characteristics in common can be grouped together to form a new visual object. Many psychophysical experiments have been proposed to measure the quantitative parameters of these laws. A particular interest of this thesis is the concept of association fields introduced by Field et al. [1993] which encodes different Gestalt principles (as good continuation, proximity). They showed that stimulus co-linearity and co-circularity play an important role for the feature of grouping. Their study showed how chances of perceiving the curvilinear path were high if the orientation of its features was the one tangent at that point and collapsed as their relative orientation deviated from being tangent...; L’objectif de cette thèse est de développer des modèles mathématiques de perception visuelle basés sur des architectures corticales et de les appliquer pour reproduire des expériences phénoménologiques ainsi que pour traiter des images naturelles. Nous nous concentrons sur les tâches de vision de bas niveau et nous sommes intéressés par le problème du groupement et de l’individuation des unités perceptives. Nous ferons face au problème de la reconstruction des figures illusoires et de la détection des vaisseaux rétiniens dans les images optiques. Ensuite, nous considérerons le problème du codage et du décodage de l’activité cérébrale du cortex visuel obtenue par Imagerie par Résonance Magnétique fonctionnelle (IRMf). Ceci permet d’estimer la structure du cortex d’un patient spécifique et éventuellement de reconstruire le stimulus visuel de l’activité IRMf, dans une stratégie “de lecture du cerveau”. La distinction entre notre approche et l’état de la littérature consiste à utiliser des modèles neuromathématiques du cortex comme connaissance a priori pour régulariser la structure estimée. Même si c’est un objectif à long terme, nous proposons une première approche pour améliorer les résultats dans ce domaine. L’ensemble du travail de cette thèse a été développé en tenant compte des résultats de la phénoménologie de la perception et des résultats de la neurophysiologie. Dans le domaine de la phénoménologie de la perception, au début du siècle dernier, la théorie de la psychologie de la Gestalt a défini l’intégration des contours et en particulier Wertheimer [1938], Kohler [1947], Kofka [1935] ont défini le regroupement des lois de perception. Celles-ci sont cruciales dans la construction d’objets visuels : les éléments avec des caractéristiques en commun peuvent être regroupés pour former un nouvel objet visuel plus grand. Des expériences psychophysiques ont été proposées pour mesurer les paramètres quantitatifs de ces lois. Un intérêt particulier de cette thèse est le concept de champ d’association introduit par Field et al. [1993] lequel code différents principes de la Gestalt (dont la bonne continuation et la proximité).Ces auteurs ont montré que la co-linéarité de stimulus et la co-circularité jouent un rôle important dans la caractéristique du groupement. Leur étude a montré comment les chances de percevoir un chemin curviligne étaient élevées si l’orientation de ses éléments était tangente à ce chemin. D’autre part, en neurophysiologie, une grande quantité d’expériences confirment que le problème du groupement et de détection des contours est effectué par le cortex visuel primaire (V1) [Hubel, 1995]. Un cadre mathématique, basé sur les instruments différentiels, a été introduit pour formaliser ces résultats. Les premiers modèles géométriques sont dus à Koenderink and van Doorn...

The objective of this thesis is to develop mathematical models of visual perception based on cortical architectures and to apply them to reproduce phenomenological experiments and to process natural images. We primarly focus on low level vision tasks and in particular we are interested in the problem of grouping and of individuation of perceptual units. In this setting we will face the problem of the reconstruction of illusory figures and the detection of retinal vessels in optical images. Then we consider the problem of encoding and decoding of the fMRI signal from in vivo acquired brain activity of visual cortex. This allows to estimate the structure of the cortex of a specific human patient and eventually to reconstruct the visual stimulus from fMRI activity, in a so called “brain reading” strategy. The difference between our approach and the state of the art literature consists in using previously defined neuromathematical models of the cortices as a-priori knowledge to regularise in vivo estimated structure. Even if it is a long term objective, we propose a first approach to improve the results in this field. The entire work of this thesis has been developed taking into account results from phenomenology of perception and results of neurophysiology.In the field of the phenomenology of perception, at the beginning of the last century, the theory of the Gestalt psychology [Wertheimer, 1938, Kohler, 1947, Kofka, 1935] defined the integration of contours and in particular they defined grouping laws underlying perception. These are crucial in the construction of visual objects: points with characteristics in common can be grouped together to form a new visual object. Many psychophysical experiments have been proposed to measure the quantitative parameters of these laws. A particular interest of this thesis is the concept of association fields introduced by Field et al. [1993] which encodes different Gestalt principles (as good continuation, proximity). They showed that stimulus co-linearity and co-circularity play an important role for the feature of grouping. Their study showed how chances of perceiving the curvilinear path were high if the orientation of its features was the one tangent at that point and collapsed as their relative orientation deviated from being tangent...; L’objectif de cette thèse est de développer des modèles mathématiques de perception visuelle basés sur des architectures corticales et de les appliquer pour reproduire des expériences phénoménologiques ainsi que pour traiter des images naturelles. Nous nous concentrons sur les tâches de vision de bas niveau et nous sommes intéressés par le problème du groupement et de l’individuation des unités perceptives. Nous ferons face au problème de la reconstruction des figures illusoires et de la détection des vaisseaux rétiniens dans les images optiques. Ensuite, nous considérerons le problème du codage et du décodage de l’activité cérébrale du cortex visuel obtenue par Imagerie par Résonance Magnétique fonctionnelle (IRMf). Ceci permet d’estimer la structure du cortex d’un patient spécifique et éventuellement de reconstruire le stimulus visuel de l’activité IRMf, dans une stratégie “de lecture du cerveau”. La distinction entre notre approche et l’état de la littérature consiste à utiliser des modèles neuromathématiques du cortex comme connaissance a priori pour régulariser la structure estimée. Même si c’est un objectif à long terme, nous proposons une première approche pour améliorer les résultats dans ce domaine. L’ensemble du travail de cette thèse a été développé en tenant compte des résultats de la phénoménologie de la perception et des résultats de la neurophysiologie. Dans le domaine de la phénoménologie de la perception, au début du siècle dernier, la théorie de la psychologie de la Gestalt a défini l’intégration des contours et en particulier Wertheimer [1938], Kohler [1947], Kofka [1935] ont défini le regroupement des lois de perception. Celles-ci sont cruciales dans la construction d’objets visuels : les éléments avec des caractéristiques en commun peuvent être regroupés pour former un nouvel objet visuel plus grand. Des expériences psychophysiques ont été proposées pour mesurer les paramètres quantitatifs de ces lois. Un intérêt particulier de cette thèse est le concept de champ d’association introduit par Field et al. [1993] lequel code différents principes de la Gestalt (dont la bonne continuation et la proximité).Ces auteurs ont montré que la co-linéarité de stimulus et la co-circularité jouent un rôle important dans la caractéristique du groupement. Leur étude a montré comment les chances de percevoir un chemin curviligne étaient élevées si l’orientation de ses éléments était tangente à ce chemin. D’autre part, en neurophysiologie, une grande quantité d’expériences confirment que le problème du groupement et de détection des contours est effectué par le cortex visuel primaire (V1) [Hubel, 1995]. Un cadre mathématique, basé sur les instruments différentiels, a été introduit pour formaliser ces résultats. Les premiers modèles géométriques sont dus à Koenderink and van Doorn...

Two competing hypotheses address neuroplasticity during early brain development: the "Kennard principle" describes the compensatory capacities of the immature developing CNS as superior to those of the adult brain, whereas the "Hebb principle" argues that the young brain is especially sensitive to insults. We provide evidence that these principles are not mutually exclusive. Following early brain lesions that are unilateral, the brain can refer to homotopic areas of the healthy hemisphere. This potential for reorganization is unique to the young brain but available only when, during ontogenesis of brain development, these areas have been used for the functions addressed. With respect to motor function, ipsilateral motor tracts can be recruited, which are only available during early brain development. Language can be reorganized to the right after early left hemispheric lesions, as the representation of the language network is initially bilateral. However, even in these situations, compensatory capacities of the developing brain are found to have limitations, probably defined by early determinants. Thus, plasticity and adaptivity are seen only within ontogenetic potential; that is, axonal or cortical structures cannot be recruited beyond early developmental possibilities. The young brain is probably more sensitive and vulnerable to lesions when these are bilateral. This is shown here for bilateral periventricular white matter lesions that clearly have an impact on cortical architecture and function, thus probably interfering with early network building.

In the last few years, several studies have revisited long-held assumptions in the field of brain development and evolution providing us with a fundamentally new vision on the mechanisms controlling its size and shape, hence function. Among these studies, some described hitherto unforeseeable subtypes of neural progenitors while others reinterpreted long-known observations about their cell cycle in alternative new ways. Most remarkably, this knowledge combined has allowed the generation of mammalian model organisms in which brain size and folding has been selectively increased giving us the means to understand the mechanisms underlying the evolution of the most complex and sophisticated organ. Here we review the key findings made in this area and make a few conjectures about their evolutionary meaning including the likelihood of Martians conquering our planet., VB and FC are supported by the Ministerio de Economía y Competitividad (BFU2012-33473) and European Research Council (309633) (VB), DFG Collaborative Research Center SFB655, Center for Regenerative Therapies and Medical Faculty of the TU–Dresden (FC).

Making good predictions about the outcome of one’s actions woul d seem to be essential in the context of social interaction and decision-making. This paper proposes a computational model for learning articulated motion patterns for action recognition, wh ich mimics biological-inspired visual perception processing of huma n brain. Developed model of cortical architecture for the unsup ervised learning of motion sequence, builds upon neurophysiological kno wledge about the cortical sites such as IT, MT, STS and specifi c neuronal representation which contribute to articulated motion perception. Experiments show how the model automatically selects significant motion patterns as well as meaningful static snapsh ot categories from continuous video input. Such key poses corre spond to articulated postures which are utilized in probing the train ed network to impose implied motion perception from static views. We also present how sequence selective representations are learned in STS by fusing snapshot and motion input and how learned feedback connections enable making predictions about future inp ut sequence. Network simulations demonstrate the computational capacity of the proposed model for motion recognition.

A distinguishing architectural property of the mammalian cortex is its segregation into gray and white matter. While universal in mammals, most nonmammalian brains do not show any sign of the same organization. In this chapter, the discussion centers around the evolutionary history of white matter—how it came to be—and what possible advantages come from having a cerebral cortex with such segregation.

A minicolumn is the smallest anatomical module in the cortical architecture, but it is still in debate whether it serves as functional units for cortical processing. In the rodent primary visual cortex (V1), neurons with different preferred orientations are mixed horizontally in a salt and pepper manner, but vertical functional organization was not examined. In this study, we found that neurons with similar orientation preference are weakly but significantly clustered vertically in a short length and horizontally in the scale of a minicolumn. Interestingly, the vertical clustering is found only in a part of minicolumns, and others are composed of neurons with a variety of orientation preferences. Thus, the mouse V1 is a mixture of vertical clusters of neurons with various degrees of orientation similarity, which may be the compromise between the brain size and keeping the vertical clusters of similarly tuned neurons at least in a subset of clusters., Primary visual cortical neurons display mostly a salt and pepper arrangement of orientation preferences along the horizontal cortical axis. Here the authors show that a significant subset of minicolumns, one-cell wide arrays of cells arranged along the vertical axis, show similar orientation tuning preferences.

Perception is subjective. Even basic judgments, like those of visual object size, vary substantially between observers and also across the visual field within the same observer. The way in which the visual system determines the size of objects remains unclear, however. We hypothesize that object size is inferred from neuronal population activity in V1 and predict that idiosyncrasies in cortical functional architecture should therefore explain individual differences in size judgments. Indeed, using novel behavioral methods and functional magnetic resonance imaging (fMRI) we demonstrate that biases in size perception are correlated with the spatial tuning of neuronal populations in healthy volunteers. To explain this relationship, we formulate a population read-out model that directly links the spatial distribution of V1 representations to our perceptual experience of visual size. Altogether, we suggest that the individual perception of simple stimuli is warped by idiosyncrasies in visual cortical organization.

The characterization of coordinated activity in neuronal populations has received renewed interest in the light of advancing experimental techniques which allow recordings from multiple units simultaneously. Across both in vitro and in vivo preparations, nearby neurons show coordinated responses when spontaneously active, and when subject to external stimuli. Recent work (Truccolo, Hochberg, & Donoghue, 2010) has connected these coordinated responses to behavior, showing that small ensembles of neurons in arm related areas of sensorimotor cortex can reliably predict single-neuron spikes in behaving monkeys and humans. We investigate this phenomenon utilizing an analogous point process model, showing that in the case of a computational model of cortex responding to random background inputs, one is similarly able to predict the future state of a single neuron by considering its own spiking history, together with the spiking histories of randomly sampled ensembles of nearby neurons. This model exhibits realistic cortical architecture and displays bursting episodes in the two distinct connectivity schemes studied. We conjecture that the baseline predictability we find in these instances is characteristic of locally connected networks more broadly considered., 29 pages, 11 figures

Anatomical studies demonstrate that excitatory connections in cortex are not uniformly distributed across a network but instead exhibit clustering into groups of highly connected neurons. The implications of clustering for cortical activity are unclear. We studied the effect of clustered excitatory connections on the dynamics of neuronal networks that exhibited high spike time variability owing to a balance between excitation and inhibition. Even modest clustering substantially changed the behavior of these networks, introducing slow dynamics during which clusters of neurons transiently increased or decreased their firing rate. Consequently, neurons exhibited both fast spiking variability and slow firing rate fluctuations. A simplified model shows how stimuli bias networks toward particular activity states, thereby reducing firing rate variability as observed experimentally in many cortical areas. Our model thus relates cortical architecture to the reported variability in spontaneous and evoked spiking activity.

The orbital and ventromedial frontal cortical regions of the human and the macaque monkey brains include several spatially discrete areas which are defined histologically by their distinctive laminar architecture. Although considerable information has been collected on the function and anatomical connections of specific architectonic areas within the orbital and ventromedial frontal cortex of the macaque monkey, the location of comparable areas in the human brain remains controversial. We re-examined the comparability of orbital and ventromedial frontal areas across these two species and provide the first quantitative demonstration of architectonically comparable cortical areas in the human and the macaque brains. Images of Nissl-stained sections of the cortex were obtained at low magnification. Differences in the typical size of neurons in alternating pyramidal and granule cell layers were exploited to segregate the cortical layers before sampling. Profiles of areal neuronal density were sampled across the width of the cortex. The location of individual cortical layers was identified on each profile by sampling a set of equally sized images on which the cortical layers had been manually traced. The rank order of sampled architectonic features in comparable architectonic areas in the two species was significantly correlated. The differences in measured features between gyral and sulcal parts of the same architectonic area are at a minimum 3-4 times smaller than the differences between architectonic areas for the areas examined. Furthermore, the quantified architectonic features arrange areas within the orbital and ventromedial frontal cortex along two dimensions: an anterior-to-posterior and a medial-to-lateral dimension. On the basis of these findings, and in light of known anatomical connections in the macaque, this region of the human cortex appears to comprise at least two hierarchically structured networks of areas.

The first paper of Hubel and Wiesel in The Journal of Physiology in 1959 marked the beginning of an exciting chapter in the history of visual neuroscience. Through a collaboration that lasted 25 years, Hubel and Wiesel described the main response properties of visual cortical neurons, the functional architecture of visual cortex and the role of visual experience in shaping cortical architecture. The work of Hubel and Wiesel transformed the field not only through scientific discovery but also by touching the life and scientific careers of many students. Here, I describe my personal experience as a postdoctoral student with Torsten Wiesel and how this experience influenced my own work.

Patients with vertebral fractures (VFx) have trabecular architectural disruption on iliac biopsies. Because cortical bone is an important determinant of bone strength, we assessed cortical and trabecular microarchitecture at peripheral sites in patients with VFx of varying number (N) and severity (S). Bone architecture and volumetric density (vBMD) were assessed at the distal radius and tibia with HR-pQCT (XTreme CT; Scanco Medical, Bassersdorf, Switzerland) in 100 women with VFx (age, 74 +/- 9 yr) of different S (GI, n = 23; GII, n = 35 ; GIII, n = 42) and in 362 women (age, 69 +/- 7 yr) without peripheral or VFx (G0) from the OFELY study. Spine areal BMD (aBMD) was assessed by DXA. Among all women, at the radius and after adjustment for age and aBMD, there were significant trends in lower vBMD, cortical thickness (Cort.Th), trabecular number (Tb.N) and thickness (Tb.Th), higher trabecular separation (Tb.Sp), and distribution of separation (Tb.Sp.SD) with greater VFx S and N. Among women with VFx, lower Cort.Th and cortical vBMD (D.Cort) were associated with severe (GIII) and multiple (n2) VFx (p0.05). The age-adjusted OR for each SD decrease of Cort.Th was 2.04 (95% CI, 1.02-4.00) after adjustment for aBMD. At the tibia, there were trends for lower vBMD, Tb.N, Tb.Th, and higher Tb.Sp and Tb.Sp.SD with greater VFx S and N (p0.001). Among women with VFx, lower Cort.Th and D.Cort were associated with severe and multiple (n3) VFx (p0.01). In postmenopausal women, VFx are associated with low vBMD and architectural decay of trabecular and cortical bone at the radius and tibia, independently of spine aBMD. Severe and multiple VFx are associated with even more alterations of cortical bone.

Recent developments in functional imaging as well as the emergence of new anatomical imaging techniques suited for the study of white matter have shifted investigational paradigms from a localized to a more holistic network approach. Aside from detecting local activity, functional MRI can be applied to the study of connectivity. However, the concept of "functional connectivity" remains broad, and specific designs and analyses may affect the results. In addition, connectivity cannot be viewed in isolation. Rather, from a developmental perspective, connectivity and local cortical architecture are intimately related. Therefore, combined approaches examining local organization and connectivity are the most promising avenues for elucidating disturbances of neurofunctional organization in developmental disorders. Here this approach is illustrated via data obtained from autism research that suggest impaired local cortical architecture and reduced long-range connectivity between cerebral regions.

The developmental principles that establish the columnar edifice of the cerebral cortex underlie its evolution and dictate its physiological operations and cognitive capacity. This article contrasts the initial discoveries made by Ramón y Cajal and his contemporaries, based on the ingenious interpretation of neuronal shapes and their relationships using the Golgi method, with new insights based on the application of the most advanced methods of molecular biology and genetics. We can now propose a realistic model of how the sequence of gene expression, cascade of multiple molecular pathways and cell-cell interactions establish the number of neurons, guide their migration and allocation into proper regions and determine their differentiation into specific phenotypes that establish specific synaptic connections. The findings obtained from different levels of analyses sustain the radial unit hypothesis as a useful framework for understanding the mechanisms of cortical development and its evolution as an organ of thought.