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The amygdaloid complex, including the basolateral nucleus (BLA), contributes crucially to emotional and cognitive brain functions, and is a major target of research in both humans and rodents. However, delineating structural amygdala plasticity in both normal and disease-related contexts using neuroimaging has been hampered by the difficulty of unequivocally identifying the boundaries of the BLA. This challenge is a result of the poor contrast between BLA and the surrounding gray matter, including other amygdala nuclei. Here, we describe a novel diffusion tensor imaging (DTI) approach to enhance contrast, enabling the optimal identification of BLA in the rodent brain from magnetic resonance (MR) images. We employed this methodology together with a slice-shifting approach to accurately measure BLA volumes. We then validated the results by direct comparison to both histological and cellular-identity (parvalbumin)-based conventional techniques for defining BLA in the same brains used for MRI. We also confirmed BLA connectivity targets using DTI-based tractography. The novel approach enables the accurate and reliable delineation of BLA. Because this nucleus is involved in and changed by developmental, degenerative and adaptive processes, the instruments provided here should be highly useful to a broad range of neuroimaging studies. Finally, the principles used here are readily applicable to numerous brain regions and across species.

Numerical research results of heat transfer in layered system “air-heated particle-skin layer” presented. Skin structure includes epidermis, derma and hypodermis layers. Skin was influenced by heated up to high temperatures particle. The problem is solved in simple one-dimensional statement in Cartesian system of coordinates. The typical range of influence parameters of heated particle considered. Temperature distributions in different moments of time obtained. Condition of burn occurrence by heated particle is under consideration in this work.

Numerical research results of heat transfer in system “air-heated particle-skin layer” presented. Skin was influenced by heated up to high temperatures particle. The problem is solved in tree-dimensional statement in Cartesian system of coordinates. The typical range of influence parameters of heated particle considered. Temperature distributions in different moments of time obtained. Condition of burn occurrence by heated particle is under consideration in this research.

Numerical research results of heated to high temperatures particle influence on human skin are presented. The problem is solved in two-dimensional statement in Cartesian system of coordinates. The typical range of influence parameters of heated particle is considered. Temperature distributionы in different moments of time are obtained.

It is developed physical and mathematical models of process of a heat transfer between skin and a heating source - single heated up to high temperatures particle. Temperature distribution in system “particle-skin” for heated wooden particle is obtained. The data obtained during work can be used for addition of already available materials on the given subjects and comparisons of influences on a skin of various factors, and also can be useful to development of new systems of protection against the influences damaging factors in the conditions of fire.

Repetitive head impacts represent a risk factor for neurological impairment in team-sport athletes. In the absence of symptoms, a physiological basis for acute injury has not been elucidated. A basic brain function that is disrupted after mild traumatic brain injury is the regulation of homeostasis, instantiated by activity across a specific set of brain regions that comprise a central autonomic network. We sought to relate head-to-ball impact exposure to changes in functional connectivity in a core set of central autonomic regions and then to determine the relation between changes in brain and changes in behavior, specifically cognitive control. Thirteen collegiate men's soccer players and eleven control athletes (golf, cross-country) underwent resting-state fMRI and behavioral testing before and after the season, and a core group of cortical, subcortical, and brainstem regions was selected to represent the central autonomic network. Head-to-ball impacts were recorded for each soccer player. Cognitive control was assessed using a Dot Probe Expectancy task. We observed that head-to-ball impact exposure was associated with diffuse increases in functional connectivity across a core CAN subnetwork. Increased functional connectivity between the left insula and left medial orbitofrontal cortex was associated with diminished proactive cognitive control after the season in those sustaining the greatest number of head-to-ball impacts. These findings encourage measures of autonomic physiology to monitor brain health in contact and collision sport athletes.

Adolescence is a complex period of concurrent mental and physical development that facilitates adult functioning at multiple levels. Despite the growing number of neuroimaging studies of cognitive development in adolescence focusing on regional activation patterns, there remains a paucity of information about the functional interactions across these participating regions that are critical for cognitive functioning, including memory. The current study used structural equation modeling (SEM) to determine how interactions among brain regions critical for memory change over the course of adolescence. We obtained functional MRI in 77 individuals aged 8-16 years old, divided into younger (ages 8-10) and older (ages > 11) cohorts, using an incidental encoding memory task to activate hippocampus formation and associated brain networks, as well as behavioral data on memory function. SEM was performed on the imaging data for four groups (younger girls, younger boys, older girls, and older boys) that were subsequently compared using a stacked model approach. Significant differences were seen between the models for these groups. Younger boys had a predominantly posterior distribution of connections originating in primary visual regions and terminating on multi-modal processing regions. In older boys, there was a relatively greater anterior connection distribution, with increased effective connectivity within association and multi-modal processing regions. Connection patterns in younger girls were similar to those of older boys, with a generally anterior-posterior distributed network among sensory, multi-modal, and limbic regions. In contrast, connections in older girls were widely distributed but relatively weaker. Memory performance increased with age, without a significant difference between the sexes. These findings suggest a progressive reorganization among brain regions, with a commensurate increase in efficiency of cognitive functioning, from younger to older individuals in both girls and boys, providing insight into the age- and gender-specific processes at play during this critical transition period.

Alzheimers disease (AD) is marked by cognitive dysfunction emerging from neuropathological processes impacting brain function. AD affects brain dynamics at the local level, such as changes in the balance of inhibitory and excitatory neuronal populations, as well as long-range changes to the global network. Individual differences in these changes as they relate to behaviour are poorly understood. Here, we use a multi-scale neurophysiological model, The Virtual Brain (TVB), based on empirical multi-modal neuroimaging data, to study how local and global dynamics correlate with individual differences in cognition. In particular, we modeled individual resting-state functional activity of 124 individuals across the behavioural spectrum from healthy aging, to amnesic Mild Cognitive Impairment (MCI), to AD. The model parameters required to accurately simulate empirical functional brain imaging data correlated significantly with cognition, and exceeded the predictive capacity of empirical connectomes.

Alzheimer's disease (AD) is marked by cognitive dysfunction emerging from neuropathological processes impacting brain function. AD affects brain dynamics at the local level, such as changes in the balance of inhibitory and excitatory neuronal populations, as well as long-range changes to the global network. Individual differences in these changes as they relate to behaviour are poorly understood. Here, we use a multi-scale neurophysiological model, "The Virtual Brain (TVB)", based on empirical multi-modal neuroimaging data, to study how local and global dynamics correlate with individual differences in cognition. In particular, we modeled individual resting-state functional activity of 124 individuals across the behavioural spectrum from healthy aging, to amnesic Mild Cognitive Impairment (MCI), to AD. The model parameters required to accurately simulate empirical functional brain imaging data correlated significantly with cognition, and exceeded the predictive capacity of empirical connectomes.

Memory and related cognitive functions are progressively impaired in a subgroup of individuals experiencing childhood adversity and stress. However, it is not possible to identify vulnerable individuals early, a crucial step for intervention. In this study, high-resolution magnetic resonance imaging (MRI) and intra-hippocampal diffusion tensor imaging (DTI) were employed to examine for structural signatures of cognitive adolescent vulnerabilities in a rodent model of early-life adversity. These methods were complemented by neuroanatomical and functional assessments of hippocampal network integrity during adolescence, adulthood and middle-age. The high-resolution MRI identified selective loss of dorsal hippocampal volume, and intra-hippocampal DTI uncovered disruption of dendritic structure, consistent with disrupted local connectivity, already during late adolescence in adversity-experiencing rats. Memory deteriorated over time, and stunting of hippocampal dendritic trees was apparent on neuroanatomical analyses. Thus, disrupted hippocampal neuronal structure and connectivity, associated with cognitive impairments, are detectable via non-invasive imaging modalities in rats experiencing early-life adversity. These high-resolution imaging approaches may constitute promising tools for prediction and assessment of at-risk individuals in the clinic. © 2016 Wiley Periodicals, Inc.

Objective Our objective was to determine whether maternal blood angiogenic factors in suspected-small-for-gestational-age (sSGA) fetuses can predict critical adverse perinatal outcomes (CAPO) and improve risk assessment. Methods Women with singleton pregnancies diagnosed with sSGA, between 24 and 35 6/7 weeks' gestation, were included. Clinical and sonographic comprehensive evaluations were performed at enrolment. Plasma angiogenic factors, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF), were obtained at diagnosis. In parallel, three attending maternal-fetal-medicine specialists predicted the risk (1–5 scale) of these pregnancies to develop CAPO, based on the clinical presentation. CAPOs were defined as prolonged neonatal intensive care unit hospitalization, fetal or neonatal death, and major neonatal morbidity. Statistical analysis included sensitivity, specificity, positive and negative predictive values, and receiver-operating characteristic (ROC) curve analyses. Results Of the 79 cases included, 32 were complicated by CAPO (40.5%). In SGA fetuses with CAPO, the sFlt-1/PlGF ratio was higher (p < 0.001) and PlGF was lower (p < 0.001) as compared with uncomplicated pregnancies. The areas under the ROC curves for specialists were 0.913, 0.824, and 0.811 and for PlGF and sFlt-1/PlGF ratio 0.926 and 0.900, respectively. CAPO was more common in pregnancies with absent end-diastolic flow or reversed end-diastolic flow (AEDF or REDF) in the umbilical artery upon enrolment (91.6%). Yet, 65.6% of cases involving CAPO occurred in patients without AEDF or REDF, and 66.6% of these cases were not identified by one or more of the experts. The sFlt-1/PlGF ratio identified 92.9% of the experts' errors in this group and 100% of the errors in cases with AEDF or REDF. Conclusion Among sSGA pregnancies prior to 36 weeks' gestation, angiogenic factors testing can identify most cases later complicated with CAPO. Our data demonstrate for the first time that these markers can reduce clinician judgment errors. Incorporation of these measures into decision-making algorithms could potentially improve management, outcomes, and even health care costs. Key Points Angiogenic factors at diagnosis of sSGA can be used to predict CAPO. The sFlt-1/PlGF ratio can flag sSGA pregnancies at increased risk. The sFlt-1/PlGF ratio at admission of sSGA adds to clinical assessment. [ABSTRACT FROM AUTHOR]

Children who sustain a prenatal or perinatal brain injury in the form of a stroke develop remarkably normal cognitive functions in certain areas, with a particular strength in language skills. A dominant explanation for this is that brain regions from the contralesional hemisphere "take over" their functions, whereas the damaged areas and other ipsilesional regions play much less of a role. However, it is difficult to tease apart whether changes in neural activity after early brain injury are due to damage caused by the lesion or by processes related to postinjury reorganization. We sought to differentiate between these two causes by investigating the functional connectivity (FC) of brain areas during the resting state in human children with early brain injury using a computational model. We simulated a large-scale network consisting of realistic models of local brain areas coupled through anatomical connectivity information of healthy and injured participants. We then compared the resulting simulated FC values of healthy and injured participants with the empirical ones. We found that the empirical connectivity values, especially of the damaged areas, correlated better with simulated values of a healthy brain than those of an injured brain. This result indicates that the structural damage caused by an early brain injury is unlikely to have an adverse and sustained impact on the functional connections, albeit during the resting state, of damaged areas. Therefore, these areas could continue to play a role in the development of near-normal function in certain domains such as language in these children.

The cognitive effects of stress are profound, yet it is unknown if the consequences of concurrent multiple stresses on learning and memory differ from those of a single stress of equal intensity and duration. We compared the effects on hippocampus-dependent memory of concurrent, hours-long light, loud noise, jostling and restraint (multimodal stress) with those of restraint or of loud noise alone. We then examined if differences in memory impairment following these two stress types might derive from their differential impact on hippocampal synapses, distinguishing dorsal and ventral hippocampus. Mice exposed to hours-long restraint or loud noise were modestly or minimally impaired in novel object recognition, whereas similar-duration multimodal stress provoked severe deficits. Differences in memory were not explained by differences in plasma corticosterone levels or numbers of Fos-labeled neurons in stress-sensitive hypothalamic neurons. However, although synapses in hippocampal CA3 were impacted by both restraint and multimodal stress, multimodal stress alone reduced synapse numbers severely in dorsal CA1, a region crucial for hippocampus-dependent memory. Ventral CA1 synapses were not significantly affected by either stress modality. Probing the basis of the preferential loss of dorsal synapses after multimodal stress, we found differential patterns of neuronal activation by the two stress types. Cross-correlation matrices, reflecting functional connectivity among activated regions, demonstrated that multimodal stress reduced hippocampal correlations with septum and thalamus and increased correlations with amygdala and BST. Thus, despite similar effects on plasma corticosterone and on hypothalamic stress-sensitive cells, multimodal and restraint stress differ in their activation of brain networks and in their impact on hippocampal synapses. Both of these processes might contribute to amplified memory impairments following short, multimodal stress.

The cognitive effects of stress are profound, yet it is unknown if the consequences of concurrent multiple stresses on learning and memory differ from those of a single stress of equal intensity and duration. We compared the effects on hippocampus-dependent memory of concurrent, hours-long light, loud noise, jostling and restraint (multimodal stress) with those of restraint or of loud noise alone. We then examined if differences in memory impairment following these two stress types might derive from their differential impact on hippocampal synapses, distinguishing dorsal and ventral hippocampus. Mice exposed to hours-long restraint or loud noise were modestly or minimally impaired in novel object recognition, whereas similar-duration multimodal stress provoked severe deficits. Differences in memory were not explained by differences in plasma corticosterone levels or numbers of Fos-labeled neurons in stress-sensitive hypothalamic neurons. However, although synapses in hippocampal CA3 were impacted by both restraint and multimodal stress, multimodal stress alone reduced synapse numbers severely in dorsal CA1, a region crucial for hippocampus-dependent memory. Ventral CA1 synapses were not significantly affected by either stress modality. Probing the basis of the preferential loss of dorsal synapses after multimodal stress, we found differential patterns of neuronal activation by the two stress types. Cross-correlation matrices, reflecting functional connectivity among activated regions, demonstrated that multimodal stress reduced hippocampal correlations with septum and thalamus and increased correlations with amygdala and BST. Thus, despite similar effects on plasma corticosterone and on hypothalamic stress-sensitive cells, multimodal and restraint stress differ in their activation of brain networks and in their impact on hippocampal synapses. Both of these processes might contribute to amplified memory impairments following short, multimodal stress.

Following stroke, patients are commonly left with debilitating motor and speech impairments. This article reviews the state of the art in neurological repair for stroke and proposes a new model for the future. We suggest that stroke treatment--from the time of the ictus itself to living with the consequences--must be fundamentally neurological, from limiting the extent of injury at the outset, to repairing the consequent damage. Our model links brain and behaviour by targeting brain circuits, and we illustrate the model though action observation treatment, which aims to enhance brain network connectivity. The model is based on the assumptions that the mechanisms of neural repair inherently involve cellular and circuit plasticity, that brain plasticity is a synaptic phenomenon that is largely stimulus-dependent, and that brain repair required both physical and behavioural interventions that are tailored to reorganize specific brain circuits. We review current approaches to brain repair after stroke and present our new model, and discuss the biological foundations, rationales, and data to support our novel approach to upper-extremity and language rehabilitation. We believe that by enhancing plasticity at the level of brain network interactions, this neurological model for brain repair could ultimately lead to a cure for stroke.

Repetitive head impacts represent a risk factor for neurological impairment in team-sport athletes. In the absence of symptoms, a physiological basis for acute injury has not been elucidated. A basic brain function that is disrupted after mild traumatic brain injury is the regulation of homeostasis, instantiated by activity across a specific set of brain regions that comprise a central autonomic network. We sought to relate head-to-ball impact exposure to changes in functional connectivity in a core set of central autonomic regions and then to determine the relation between changes in brain and changes in behavior, specifically cognitive control. Thirteen collegiate men's soccer players and eleven control athletes (golf, cross-country) underwent resting-state fMRI and behavioral testing before and after the season, and a core group of cortical, subcortical, and brainstem regions was selected to represent the central autonomic network. Head-to-ball impacts were recorded for each soccer player. Cognitive control was assessed using a Dot Probe Expectancy task. We observed that head-to-ball impact exposure was associated with diffuse increases in functional connectivity across a core CAN subnetwork. Increased functional connectivity between the left insula and left medial orbitofrontal cortex was associated with diminished proactive cognitive control after the season in those sustaining the greatest number of head-to-ball impacts. These findings encourage measures of autonomic physiology to monitor brain health in contact and collision sport athletes.

Maternal sensory signals in early life play a crucial role in programming the structure and function of the developing brain, promoting vulnerability or resilience to emotional and cognitive disorders. In rodent models of early-life stress, fragmentation and unpredictability of maternally derived sensory signals provoke persistent cognitive and emotional dysfunction in offspring. Similar variability and inconsistency of maternal signals during both gestation and early postnatal human life may influence development of emotional and cognitive functions, including those that underlie later depression and anxiety.

The first phase of major neuronal rearrangements in the brain takes place during the prenatal period. While the brain continues maturation throughout childhood, a critical second phase of synaptic overproduction and elimination takes place during the preadolescent period. Despite the importance of this developmental phase, few studies have evaluated neural changes taking place during this period. In this study, MRI Diffusion Tensor Imaging data from a normative sample of 126 preadolescent children (59 girls and 67 boys) between the ages of 6 and 10 years were analyzed in order to characterize age-relationships in the white matter microstructure. Tract Based Spatial Statistics (TBSS) method was used for whole brain analysis of white matter tracts without a priori assumption about the location of age associated differences. Our results demonstrate significant age-associated differences in most of the major fiber tracts bilaterally and along the whole body of the tracts. In contrast, developmental differences in the cingulum at the level of the parahippocampal region were only observed in the right hemisphere. We suggest that these age-relationships with a widespread distribution seen during the preadolescent years maybe relevant for the implementation of cognitive and social behaviors needed for a normal development into adulthood.

Much evidence has now accumulated demonstrating and quantifying the extent of shared regional brain activation for observation and execution of speech. However, the nature of the actual networks that implement these functions, i.e., both the brain regions and the connections among them, and the similarities and differences across these networks has not been elucidated. The current study aims to characterize formally a network for observation and imitation of syllables in the healthy adult brain and to compare their structure and effective connectivity. Eleven healthy participants observed or imitated audiovisual syllables spoken by a human actor. We constructed four structural equation models to characterize the networks for observation and imitation in each of the two hemispheres. Our results show that the network models for observation and imitation comprise the same essential structure but differ in important ways from each other (in both hemispheres) based on connectivity. In particular, our results show that the connections from posterior superior temporal gyrus and sulcus to ventral premotor, ventral premotor to dorsal premotor, and dorsal premotor to primary motor cortex in the left hemisphere are stronger during imitation than during observation. The first two connections are implicated in a putative dorsal stream of speech perception, thought to involve translating auditory speech signals into motor representations. Thus, the current results suggest that flow of information during imitation, starting at the posterior superior temporal cortex and ending in the motor cortex, enhances input to the motor cortex in the service of speech execution.

Alzheimer's disease (AD) is marked by cognitive dysfunction emerging from neuropathological processes impacting brain function. AD affects brain dynamics at the local level, such as changes in the balance of inhibitory and excitatory neuronal populations, as well as long-range changes to the global network. Individual differences in these changes as they relate to behaviour are poorly understood. Here, we use a multi-scale neurophysiological model, “The Virtual Brain (TVB)”, based on empirical multi-modal neuroimaging data, to study how local and global dynamics correlate with individual differences in cognition. In particular, we modeled individual resting-state functional activity of 124 individuals across the behavioural spectrum from healthy aging, to amnesic Mild Cognitive Impairment (MCI), to AD. The model parameters required to accurately simulate empirical functional brain imaging data correlated significantly with cognition, and exceeded the predictive capacity of empirical connectomes.

Formed in its final form in the middle of the 17th century, the Piskarevsky chronicle, based on the original part of which are “notes” of a Moscow official, contains quite lengthy entries devoted to the Crimean raids of 1571, 1572 and 1591 on the Russian capital, as well as the Serpukhov campaign of Tsar Boris Fedorovich. These entries, published according to the style and range of interests, from the pen of one person, preserved many unique, often quite reliable information (especially about Moscow's fire in May 1571 and battles near it after two decades), pass on an oral tradition (revealed in some other narrative memorials of that time) or captured the memories of a contemporary, although sometimes they show certain dependence on “ranks”.

The reconciliation of theories of concepts based on prototypes, exemplars, and theory-like structures is a longstanding problem in cognitive science. In response to this problem, researchers have recently tended to adopt either hybrid theories that combine various kinds of representational structure, or eliminative theories that replace concepts with a more finely grained taxonomy of mental representations. In this paper, we describe an alternative approach involving a single class of mental representations called "semantic pointers." Semantic pointers are symbol-like representations that result from the compression and recursive binding of perceptual, lexical, and motor representations, effectively integrating traditional connectionist and symbolic approaches. We present a computational model using semantic pointers that replicates experimental data from categorization studies involving each prior paradigm. We argue that a framework involving semantic pointers can provide a unified account of conceptual phenomena, and we compare our framework to existing alternatives in accounting for the scope, content, recursive combination, and neural implementation of concepts.

The subject of the study is the definition of the sources of the articles of the Siberian chronicle code (beginning with its early edition – the Kniga Zapisnaya, or the Registry Book) dedicated to the emergence of the Kuznetsk and Yenisei stockade settlements. The purpose of the paper is to compare chronicle news in the context of the narrative of anonymous scribes about the resumption of the Russian urban planning in Siberia beginning with the enthronement of Tsar Mikhail Fedorovich. The main method of analysis is the comparison of the reports with each other as well as with documentary evidence. As a result, it appears that the creators of the code, in particular, the protograph of its early editions, turned to the replies of the Tobolsk, theh Kuznetsk, and the Yenissei administrators on the construction of new Russian stockades on the banks of the Tom and the Yenissei rivers in 1618– 1619. The field of application of observations concerning the origin of the articles of interest is the history of Siberian chronicle writing and the Russian colonization of Siberia in the first quarter of the 17th century. The conclusions are substantiated by the articles of the initial editions of the Siberian chronicle that are based on documentary sources. The testimony of the first Yenissei voivode Ya. I. Khripunov, the creator of the Kniga Zapisnaya, was omitted in later versions but apparently conveys memories that date back to the mid-17th century. During the editing and copying of the code, a number of inaccuracies occurred, but most of the information given in the annals can be considered rather reliable. The further history of the articles under consideration in many respects reflects the evolution of the Siberian literary tradition in the 17th century.

Крымское нашествие на Москву летом 1591 г., оказавшееся последним в длительной истории двусторонних отношений, получило отражение наряду с летописными сочинениями в русской публицистике кануна Смутного времени и 1620-х гг. Упоминание (не отличающееся точностью) о неудачной попытке Гази-Гирея II овладеть российской столицей, восходящее к какому-то краткому летописцу, имеется в Хронографе второй редакции. В Повести о царе Федоре Ивановиче, написанной патриархом Иовом, и Временнике дьяка Ивана Тимофеева мы встречаем пространные рассказы, посвященные боям под Москвой между татарами и войском, фактическим главнокомандующим которого являлся Борис Годунов. Используя летописный источник (видимо, тот, который В. Н. Татищев назвал «Историей о разорении русском»), Иов тенденциозно изобразил правителя Бориса выдающимся полководцем и подчеркнул значение молитв о заступничестве, обращенных к Богу и Богородице «освятованным» царем Федором. Между прочим, победа, одержанная над крымцами у стен Москвы, под пером «смиренного» патриарха делала шурина бездетного государя его достойным наследником. Иван Тимофеев же, писавший по собственным воспоминаниям спустя два десятилетия, если не позднее, о быстром бегстве татар из окрестностей «царствующего града», представил Годунова (в том числе под впечатлением Серпуховского похода 1598 г.) «лжехрабрым» военачальником, а главную роль в разгроме хана отвел мольбам подобного святым самодержца, в конце жизни которого с Крымом установились мирные отношения. / The Crimean Tatar invasion of Moscow in the summer of 1591 was the last in the long history of bilateral relations, and it is reflected along with chronicle writings in the Russian journalism on the eve of the Time of Troubles and the 1620s. Mention (not very accurate) about the failed attempt by Gazi Giray II to master the Russian capital, rising to some brief chronicler, available in the second edition of the Chronograph. The Tale of Tsar Fyodor Ivanovich, written by the patriarch Iov, and Annals clerk Ivan Timofeev we encounter lengthy stories devoted to battles near Moscow, between the Tatars and the army, which was the de facto commander of Boris Godunov. Using chronicle source (probably the one that V. N. Tatischev called “History of the Destruction of Russia”), Iov tendentiously portrayed ruler Boris as an outstanding military leader and stressed the importance of prayers for the intercession addressed to God and the Virgin Mary by “saint” Tsar Fedor. By the way, the victory won over the Crimeans at the walls of Moscow, under the pen of “humility” of the patriarch did childless brother in law of the sovereign of his worthy successor. Ivan Timofeev also, writing on his own memoirs after two decades, if not later, the rapid flight of the Tatars from the vicinity of “imperial city”, presented Godunov (including under the influence of Serpukhov march 1598) as a “false courage” commander, and a leading role in the Khan defeat of this holy prayers autocrat, at the end of life is the Crimea have established peaceful relations.

Introduction: While the prevalence of neurodegenerative diseases associated with dementia such as Alzheimer's disease (AD) increases, our knowledge on the underlying mechanisms, outcome predictors, or therapeutic targets is limited. In this work, we demonstrate how computational multi-scale brain modeling links phenomena of different scales and therefore identifies potential disease mechanisms leading the way to improved diagnostics and treatment.Methods: The Virtual Brain (TVB; thevirtualbrain.org) neuroinformatics platform allows standardized large-scale structural connectivity-based simulations of whole brain dynamics. We provide proof of concept for a novel approach that quantitatively links the effects of altered molecular pathways onto neuronal population dynamics. As a novelty, we connect chemical compounds measured with positron emission tomography (PET) with neural function in TVB addressing the phenomenon of hyperexcitability in AD related to the protein amyloid beta (Abeta). We construct personalized virtual brains based on an averaged healthy connectome and individual PET derived distributions of Abeta in patients with mild cognitive impairment (MCI, N = 8) and Alzheimer's Disease (AD, N = 10) and in age-matched healthy controls (HC, N = 15) using data from ADNI-3 data base (http://adni.loni.usc.edu). In the personalized virtual brains, individual Abeta burden modulates regional Excitation-Inhibition balance, leading to local hyperexcitation with high Abeta loads. We analyze simulated regional neural activity and electroencephalograms (EEG).Results: Known empirical alterations of EEG in patients with AD compared to HCs were reproduced by simulations. The virtual AD group showed slower frequencies in simulated local field potentials and EEG compared to MCI and HC groups. The heterogeneity of the Abeta load is crucial for the virtual EEG slowing which is absent for control models with homogeneous Abeta distributions. Slowing phenomena primarily affect the network hubs, independent of the spatial distribution of Abeta. Modeling the N-methyl-D-aspartate (NMDA) receptor antagonism of memantine in local population models, reveals potential functional reversibility of the observed large-scale alterations (reflected by EEG slowing) in virtual AD brains.Discussion: We demonstrate how TVB enables the simulation of systems effects caused by pathogenetic molecular candidate mechanisms in human virtual brains.

В принятой ее издателями за Московский летописец компиляции, сложившейся скорее всего в конце царствования Михаила Федоровича, нашел отражение ряд важнейших событий русско-крымских отношений последней трети XVI в.: Молодинская битва (о ней рассказано в пространной повести, сохранившей впечатления очевидца), нашествие хана Гази Гирея II на Москву в 1591 г., заключение двустороннего соглашения в самом начале «державства» Бориса Федоровича. Целью статьи является определение источников и степени достоверности соответствующих известий изучаемого памятника. Она достигается посредством сравнения так называемого Московского летописца с другими нарративными сочинениями, а также документами, в которых имеются сведения о боях 1572 и 1591 гг. под Москвой и русско-крымских переговорах 1598 г. в Серпухове. Один из этих источников, благодаря которому можно проследить перипетии Молодинской битвы, вероятно, сложился в Разрядном приказе. О поражении, нанесенном русскими полками войскам Гази Гирея II близ Москвы, составителю рассматриваемого летописца, надо думать, стало известно по разрядной книге с записями дворян Яновых. Сведениями о подтверждении русско-крымского мира в 1598 г. компилятор, видимо, был обязан повести, раскрывающей обстоятельства воцарения Бориса Годунова. A compilation, presumably created in Mikhail Fyodorovich’s late reign and mistaken by its publishers for the Moscovite Chronicle, reflects a number of key developments in the Russian-Crimean relations in the final quarter of the 16th century, such as the Molodinskaya battle, pictured in a lengthy witness-based tale, khan Gazi Giray II assault of Moscow in 1591, and the conclusion of a bilateral agreement in the very early days of Boris Fyodorovich’s reign. The objective of this paper is to establish the sources and the reliability of the evidence in the work under consideration, which is achieved by means of comparing the so-called Moscovite Chronicle to other narrative works, alongside other official records pertaining to 1572 and 1591 skirmishes near Moscow as well as the 1598 Russian-Crimean talks in Serpukhov. One of suchlike sources, contributing to tracing the details of the Molodinskaya battle, is most likely to have originated in the Department of Appointments and Ranks (Russian Razryadnyi Prikaz). The tale of Russian troops defeating Gazi Giray II detachments near Moscow appears to have originated from a book of appointments and ranks, annotated by the Yanovs noblemen. The author of the compilation in question owes the evidence on the 1598 Russian-Crimean peace treaty to a tale specifying the circumstances of Boris Godunov’s enthronement.