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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.

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.

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.

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.

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.

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.

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).

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

Item does not contain fulltext Understanding the amazingly complex human cerebral cortex requires a map (or parcellation) of its major subdivisions, known as cortical areas. Making an accurate areal map has been a century-old objective in neuroscience. Using multi-modal magnetic resonance images from the Human Connectome Project (HCP) and an objective semi-automated neuroanatomical approach, we delineated 180 areas per hemisphere bounded by sharp changes in cortical architecture, function, connectivity, and/or topography in a precisely aligned group average of 210 healthy young adults. We characterized 97 new areas and 83 areas previously reported using post-mortem microscopy or other specialized study-specific approaches. To enable automated delineation and identification of these areas in new HCP subjects and in future studies, we trained a machine-learning classifier to recognize the multi-modal 'fingerprint' of each cortical area. This classifier detected the presence of 96.6% of the cortical areas in new subjects, replicated the group parcellation, and could correctly locate areas in individuals with atypical parcellations. The freely available parcellation and classifier will enable substantially improved neuroanatomical precision for studies of the structural and functional organization of human cerebral cortex and its variation across individuals and in development, aging, and disease.

Female Tg rasH2 (CB6F1/Jic-TgrasH2@Tac) mice were administered water once daily, water twice daily with 8 or 12 hours between doses, 1% sodium dodecyl sulfate in water (1% SDS) once daily, or 1% SDS twice daily with 12 hours between doses by oral gavage at volumes of 10 ml/kg/day for 28 or 29 consecutive days. A control group of mice received no treatment and no sham manipulation. There were no significant differences in body weight or food consumption between treated groups and untreated control mice. Mean weights of spleens, livers, and thymuses were lower than control values in most groups of mice subjected to gavage. Focal or multifocal loss of thymic cortical architecture was observed in 13 of 50 mice distributed among all groups (including naïve controls), however only in one instance was this finding suggestive of a precursor to neoplasia. This study demonstrated that Tg rasH2 mice can tolerate once or twice daily gavage dosing with water or vehicle containing 1% SDS. Loss of thymic cortical architecture was a common incidental finding in female Tg rasH2 mice.

Even in absence of sensory stimuli cortical networks exhibit complex, self-organized activity patterns. While the function of those spontaneous patterns of activation remains poorly understood, recent studies both in vivo and in vitro have demonstrated that neocortical neurons activate in a surprisingly similar sequential order both spontaneously and following input into cortex. For example, neurons that tend to fire earlier within spontaneous bursts of activity also fire earlier than other neurons in response to sensory stimuli. These “default patterns” can last hundreds of milliseconds and are strongly conserved under a variety of conditions. In this paper, we will review recent evidence for these default patterns at the local cortical level. We speculate that cortical architecture imposes common constraints on spontaneous and evoked activity flow, which result in the similarity of the patterns.

The cerebral cortex is a vastly complex structure consisting of multiple distinct populations of neurons residing in functionally specialized cortical compartments. A fundamental goal in systems neuroscience is to understand the interactions among cortical neurons and their relationship to behavior. It is hypothesized that dynamic activity patterns, such as oscillations in global neuronal activity, could span large, heterogeneous populations of cortical neurons in such a manner as to bind together the activity of otherwise disparate cortical networks. Little is know about the mechanisms by which such global oscillatory patterns entrain cortical networks or the contribution of such activity patterns to cortical function. An important step toward elucidating the role of such patterned activity in cortical information processing is understanding these interactions at the local circuit level. Here, we highlight recent findings that provide insight into how dynamic activity patterns affect specific neuronal populations and circuits.

During the first 1 to 2 h of the classical migraine attack a hypoperfusion develops which starts in the posterior part of the brain and progresses anteriorly at a rate of 2-3mm/min. The hypoperfusion stops at primary sulci outlining major cortical macro-and microstructural changes, but seems not to be inhibited by other changes of the cortical architecture. The low flow regions are cortical and the low flow persists for 4–6 h, until the attack abates. Regions of hyperperfusion are either minor or non-existent. A similar behavior characterizes the velocity and mode of evolution of a cortical spreading depression, a transient perturbation of cortical neuronal function which has profound and long-lasting influence on the cortical blood flow. This paper briefly summarizes the arguments which have been put forward in recent years suggesting that spreading depression is a pathogenetic mechanism of migraine.

The primary visual cortex of many mammals contains a continuous representation of visual space, with a roughly repetitive aperiodic map of orientation preferences superimposed. It was recently found that orientation preference maps (OPMs) obey statistical laws which are apparently invariant among species widely separated in eutherian evolution. Here, we examine whether one of the most prominent models for the optimization of cortical maps, the elastic net (EN) model, can reproduce this common design. The EN model generates representations which optimally trade of stimulus space coverage and map continuity. While this model has been used in numerous studies, no analytical results about the precise layout of the predicted OPMs have been obtained so far. We present a mathematical approach to analytically calculate the cortical representations predicted by the EN model for the joint mapping of stimulus position and orientation. We find that in all the previously studied regimes, predicted OPM layouts are perfectly periodic. An unbiased search through the EN parameter space identifies a novel regime of aperiodic OPMs with pinwheel densities lower than found in experiments. In an extreme limit, aperiodic OPMs quantitatively resembling experimental observations emerge. Stabilization of these layouts results from strong nonlocal interactions rather than from a coverage-continuity-compromise. Our results demonstrate that optimization models for stimulus representations dominated by nonlocal suppressive interactions are in principle capable of correctly predicting the common OPM design. They question that visual cortical feature representations can be explained by a coverage-continuity-compromise.