Coupling and stochasticity in mesoscopic brain dynamics

The brain is known to operate under the constant influence of noise arising from a variety of sources. It also organises its activity into rhythms spanning multiple frequency bands. These rhythms originate from neuronal oscillations which can be detected via measurements such as electroen-cephalography (EEG) and functional magnetic resonance (fMRI). Experimental evidence suggests that interactions between rhythms from distinct frequency bands play a key role in brain processing, but the dynamical mechanisms underlying this cross-frequency interactions are still under investigation. Some rhythms are pathological and harmful to brain function. Such is the case of epileptiform rhythms characterising epileptic seizures. Much has been learnt about the dynamics of the brain from computational modelling. Particularly relevant is mesoscopic scale modelling, which is concerned with spatial scales exceeding those of individual neurons and corresponding to processes and structures underlying the generation of signals registered in the EEG and fMRI recordings. Such modelling usually involves assumptions regarding the characteristics of the background noise, which represents afferents from remote, non-modelled brain areas. To this end, Gaussian white noise, characterised by a flat power spectrum, is often used. In contrast, macroscopic fluctuations in the brain typically follow a `1/f b ¿ spectrum, which is a characteristic feature of temporally correlated, coloured noise. In Chapters 3-5 of this Thesis we address by means of a stochastically driven mesoscopic neuronal model, the three following questions. First, in Chapter 3 we ask about the significance of deviations from the assumption of white noise in the context of brain dynamics, and in particular we study the role that temporally correlated noise plays in eliciting aberrant rhythms in the model of an epileptic brain. We find that the generation of epileptiform dynamics in the model depends non-monotonically on the noise correlation time. We show that this is due to the maximisation of the spectral content of epileptogenic rhythms in the noise. These rhythms fall into frequency bands that indeed were experimentally shown to increase in power prior to epileptic seizures. We explain these effects in terms of the interplay between specific driving frequencies and bifurcation structure of the model. Second, in Chapter 4 we show how coupling between cortical modules leads to complex activity patterns and to the emergence of a phenomenon that we term collective excitability. Temporal patterns generated by this model bear resemblance to clinically observed characteristics of epileptic seizures. In that chapter we also introduce a fast method of tracking a loss of stability caused by excessive inter-modular coupling in a neuronal network. Third, in Chapter 5 we focus on cross-frequency interactions occurring in a network of cortical modules, in the presence of coloured noise. We suggest a mechanism that underlies the increase of power in a fast rhythm due to driving with a slow rhythm, and we find the noise parameters that best recapitulate experimental power spectra. Finally, in Chapter 6, we examine models of haemodynamic and metabolic brain processes, we test them on experimental data, and we consider the consequences of coupling them with mesoscopic neuronal models. Taken together, our results show the combined influence of noise and coupling in computational models of neuronal activity. Moreover, they demonstrate the relevance of dynamical properties of neuronal systems to specific physiological phenomena, in particular related to cross-frequency interactions and epilepsy. Insights from this Thesis could in the future empower studies of epilepsy as a dynamic disease, and could contribute to the development of treatment methods applicable to drug-resistant epileptic patients.El cervell opera sota la influència de sorolls amb diversos orígens. També organitza la seva activitat en una sèrie de ritmes que s'expandeixen en diverses bandes de freqüència. Aquests ritmes tenen el seu origen en les osci∙lacions neuronals i poden detectar-se via mesures com les electroencefalogràfiques (EEG) o la ressonància magnètica funcional (fMRI). Les evidències experimentals suggereixen que les interaccions entre ritmes operant en bandes de freqüència diferents juguen un paper central en el processat cerebral però els mecanismes dinàmics subjacents a les interaccions inter-freqüència encara estan investigant-se. Alguns ritmes són patològics i fan malbé el funcionament cerebral. És el cas dels ritmes epileptiformes que caracteritzen les convulsions epilèptiques. Fent servir el modelatge computacional s'ha après molt sobre la dinàmica del cervell. Especialment rellevant és el modelatge a l’escala mesoscòpica, que té a veure amb les escales espacials superiors a les de les neurones individuals i que correspon als processos que generen EEG i fMRI. Tal modelatge, en general, implica supòsits relatius a les característiques del soroll de fons que representa zones remotes del cervell no modelades. Amb aquesta finalitat s'utilitza sovint el soroll blanc gaussià, que es caracteritza per un espectre de potència pla. Les fluctuacions macroscòpiques en el cervell, però, normalment segueixen un espectre '1/fb', que és un tret característic de les correlacions temporals i el soroll de color. Als Capítols 3-5 d'aquesta tesi abordem mitjançant un model neuronal mesoscòpic forçat estocàsticament, les tres preguntes següents. En primer lloc, en el Capítol 3 ens preguntem sobre la importància de les desviacions de l'assumpció de soroll blanc en el context de la dinàmica del cervell i, en particular, estudiem el paper que juga el soroll amb correlació temporal en l'obtenció de ritmes aberrants d'un cervell epilèptic. Trobem que la generació de les dinàmiques epileptiformes depèn de forma monòtona del temps de correlació del soroll. Aquests ritmes es divideixen en bandes de freqüència que, segons, s'ha mostrat experimentalment, augmenten la seva potència espectral abans de les crisis epilèptiques. Expliquem aquests efectes en termes de la interacció entre les freqüències específiques del forçament i l'estructura de bifurcació del model. En segon lloc, en el Capítol 4 es mostra com l'acoblament entre mòduls corticals condueix a patrons d'activitat complexes i a l'aparició d'un fenomen que anomenem excitabilitat col∙lectiva. Els patrons temporals generats per aquest model s'assemblen a les observacions clíniques de les convulsions epilèptiques. En aquest capítol també introduïm un mètode d'anàlisi de la pèrdua d'estabilitat causada per l'acoblament inter-modular excessiu en les xarxes neuronals. En tercer lloc, en el Capítol 5 ens centrem en les interaccions inter-freqüència que es produeixen en una xarxa de mòduls corticals en presència de soroll de color. Suggerim un mecanisme subjacent a l'augment de la potència spectral de ritmes ràpids a causa del forçament amb un ritme lent, i veiem quins paràmetres del soroll descriuen millor els espectres de potència experimental. Finalment, en el Capítol 6, estudiem models dels processos hemodinàmics i metabòlics del cervell, els comparem amb dades experimentals i considerem les conseqüències del seu acoblament amb models neuronals mesoscopics. En conjunt, els nostres resultats mostren la influència combinada del soroll i l'acoblament en models computacionals de l'activitat neuronal. D'altra banda, també demostren la importància de les propietats dinàmiques dels sistemes neuronals en fenòmens fisiològics específics com les interaccions inter-frequència i l'epilèpsia. Els resultats d'aquesta Tesi contribueixen a potenciar l’estudi de l'epilèpsia com una malaltia dinàmica, i el desenvolupament de mètodes de tractament aplicables a pacients epilèptics resistents als fàrmacs.Postprint (published version

Mięsakorak nerki współistniejący z rakiem z komórek przejściowych moczowodu - opis przypadku

This paper presented patient treated for tumor of left epigastrium. During the operation tumor of kidney was found. Histopatological examination developed two completely different types of neoplasm (sarcomatoid renal cell carcinoma and transitional cell carcinoma of ureter) located in kidney and ureter. Concomitantion of this two type neoplasm in urinary system is very rare.W pracy przedstawiono przypadek chorego operowanego z powodu guza lewego śródbrzusza, u którego śródoperacyjnie stwierdzono guza nerki. W badaniu histopatologicznym znaleziono dwa różne raki (sarcomatoid renal cell carcinoma oraz transitional cell carcinoma of ureter) wychodzące z nerki oraz moczowodu. Skojarzone występowanie nowotworów dwóch różnych rodzajów komórek w obrębie układu moczowego jest zjawiskiem rzadkim

Higher order clustering coefficients in Barabasi-Albert networks

Higher order clustering coefficients $C(x)$ are introduced for random networks. The coefficients express probabilities that the shortest distance between any two nearest neighbours of a certain vertex $i$ equals $x$, when one neglects all paths crossing the node $i$. Using $C(x)$ we found that in the Barab\'{a}si-Albert (BA) model the average shortest path length in a node's neighbourhood is smaller than the equivalent quantity of the whole network and the remainder depends only on the network parameter $m$. Our results show that small values of the standard clustering coefficient in large BA networks are due to random character of the nearest neighbourhood of vertices in such networks.Comment: 10 pages, 4 figure

A water-soluble [60]fullerene-derivative stimulates chlorophyll accumulation and has no toxic effect on Chlamydomonas reinhardtii

Chlamydomonas reinhardtii (WT 2137) P. A. Dang. (Volvocales, Chlorophyceae) is a green microalgae serving as a suitable model in scientific research and a promising industrial biotechnology platform for production of biofuel, hydrogen and recombinant proteins. Fullerenes (C60) are allotropic carbon nanoparticles discovered in 1985 and used in biomedical studies since the early 1990s, when water solubilization methodologies were developed. Recently, surface-modified hydroxylated derivatives of fullerenes were proven to enhance algal growth and drought tolerance in plants. Here, a novel type of water-soluble [60]fullerene derivative with 12 glycine residues (GF) has been synthesized and tested for acute toxicity (up to 50 μg/ml) and as a potential biostimulant of algal growth. The effects of GF on pigment composition and growth rate of Chlamydomonas reinhardtii were systematically investigated. Our results suggest that GF was not toxic, and no negative change in the pigment content and no stress symptoms were observed. No changes in the photosynthetic parameters based on the fluorescence of chlorophyll a in Photosystem II (NPQ, Fv/Fm, Fv/F0, PI and RC/ABS) were observed. The GF had no effect on cell size and growth rate. At a concentration of 20 μg/ml, GF stimulated chlorophyll accumulation in 3-day-old cultures

Podścieliskowe guzy przewodu pokarmowego (GIST)

Gastrointestinal stromal tumors (GIST) originate from the mezenchymal tissue of gastrointestinal tract, most probably from interstitial (Cajal) cells. Being the most common mesenchymal malignancy, GISTs concern no more than 1% of all gastrointestinal neoplasmatic tumors. Stromal tumors appear in the elderly and are usually located in the stomach (70%) and the small intestine (20–30%). About 30% of GISTs are malignant with signs of organ infiltration or with the presence of distant metastases. The presence of the membrane protein KIT (positive reaction against CD 117 in immunohistochemistry) in histological material is the essential factor for the GIST diagnosis. Surgery is the most important method in the treatment of GISTs. The paper presents the authors’ own experience concerning 4 patients with gastrointestinal stromal tumors treated surgically.Podścieliskowe guzy przewodu pokarmowego (GIST) wywodzą się z tkanki mezenchymalnej przewodu pokarmowego, najprawdopodobniej z komórek rozrusznikowych, tak zwanych komórek Cajala. Guzy podścieliskowe są najczęstszymi nowotworami mezenchymalnymi, stanowią jednak mniej niż 1% wszystkich nowotworów przewodu pokarmowego. Występują najczęściej u osób starszych i są przeważnie zlokalizowane w żołądku (70%) i jelicie cienkim (20–30%). Około 30% GIST wykazuje cechy złośliwości z objawami naciekania i tworzeniem przerzutów. Czynnikiem decydującym dla rozpoznania GIST jest obecność błonowego białka receptorowego KIT (dodatni odczyn anty CD 117 w badaniu immunohistochemicznym) w preparatach histopatologicznych guza. Zasadniczym sposobem terapii GIST jest leczenie operacyjne. W pracy przedstawiono doświadczenia autorów niniejszej pracy w diagnostyce oraz leczeniu GIST na podstawie grupy 4 chorych w wieku 48–71 lat leczonych chirurgicznie w ośrodku autorów

Theoretical validity and reliability of Vespide Quality of Life Questionnaire in Polish adolescents with Hymenoptera venom allergy

Measurement of health-related quality of life is mostly used with advanced measurement tools, such as scales. The use of a certain scale in different cultural settings or in age groups other than those it was designed for needs conducting the adaptation process and assessment of psychometric properties of the adapted scale. This paper presents the results of theoretical validity and reliability analysis of the Polish adaptation of the VQLQ scale for adolescents with Hymenoptera venom allergy. The study sample consisted of 78 adolescents aged 14-19 years, who were treated with venom immunotherapy in Polish allergological centers in 2008 year. Theoretical validity of the scale was analyzed with exploratory factor analysis using the principal components method. Reliability analysis was assessed in terms of internal consistency with Cronbach's α coefficient and by testing Kline's criterion. The results showed satisfactory validity of the scale: factor analysis revealed a 3-factor structure of the scale - extracted factors were described as anxiety, caution and discomfort. All the scale items contributed to unique factors, except for one item concerning limitation in summer due to allergy, which was identified as a separate dimension of health-related quality of life of Polish adolescents with Hymenoptera venom allergy. All the extracted subscales were characterized by values of α coefficient equal or higher than 0.8, what is usually considered as a high-level reliability coefficient. The adapted scale is a valid and reliable tool measuring health-related quality of life in Polish adolescents treated with venom-specific immunotherapy

Health-related quality of life in Polish adolescents with "Hymenoptera" venom allergy treated with venom immunotherapy

Introduction: Venom allergy, though rare, may seriously influence health-related quality of life (HRQoL). There is a paucity of research on HRQoL of adolescents and young adults with Hymenoptera venom allergy. The aim was to assess the level of HRQoL and to evaluate its independent predictors in Polish adolescents and young adults treated with venom immunotherapy. Material and methods: A multicenter cross-sectional study based on the Vespid Allergy Quality of Life Questionnaire (VQLQ) adapted for Polish adolescents was used. The study sample included 87 patients (14-21 years) studied at different stages of venom immunotherapy (VIT). Statistical analysis was done with multivariate linear regression. Results: Anxiety level was higher in patients with 4th grade of Mueller’s classification (anaphylactic shock) than in those with 3rd grade (B = 0.84, 95% CI = 0.07-1.61, p = 0.03). Caution increased along with an increase of anxiety of adolescents treated with VIT (B = 0.54, 95% CI = 0.39-0.68, p < 0.01). Level of limitations increased with increasing caution of adolescents (B = 0.63, 95% CI = 0.35-0.91, p < 0.01). Discomfort increased along with a rise of caution of patients (B = 0.38, 95% CI = 0.22-0.55, p < 0.01). Similarly, it increased with an increase of their feeling of limitations (B = 0.37, 95% CI = 0.23-0.51, p < 0.01). The level of discomfort in adolescents treated with VIT was lower in those who were treated with conventional protocol in comparison to those treated with rush or ultrarush ones (B = –0.47, 95% CI = –0.90 - –0.03, p = 0.04). Conclusions: Severity of anaphylactic reaction is an independent determinant of anxiety level in adolescents treated with VIT. The VIT protocol affects HRQoL of treated patients

Probabilistic functional tractography of the human cortex revisited

In patients with pharmaco-resistant focal epilepsies investigated with intracranial electroencephalography (iEEG), direct electrical stimulations of a cortical region induce cortico-cortical evoked potentials (CCEP) in distant cerebral cortex, which properties can be used to infer large scale brain connectivity. In 2013, we proposed a new probabilistic functional tractography methodology to study human brain connectivity. We have now been revisiting this method in the F-TRACT project (f-tract.eu) by developing a large multicenter CCEP database of several thousand stimulation runs performed in several hundred patients, and associated processing tools to create a probabilistic atlas of human cortico-cortical connections. Here, we wish to present a snapshot of the methods and data of F-TRACT using a pool of 213 epilepsy patients, all studied by stereo-encephalography with intracerebral depth electrodes. The CCEPs were processed using an automated pipeline with the following consecutive steps: detection of each stimulation run from stimulation artifacts in raw intracranial EEG (iEEG) files, bad channels detection with a machine learning approach, model-based stimulation artifact correction, robust averaging over stimulation pulses. Effective connectivity between the stimulated and recording areas is then inferred from the properties of the first CCEP component, i.e. onset and peak latency, amplitude, duration and integral of the significant part. Finally, group statistics of CCEP features are implemented for each brain parcel explored by iEEG electrodes. The localization (coordinates, white/gray matter relative positioning) of electrode contacts were obtained from imaging data (anatomical MRI or CT scans before and after electrodes implantation). The iEEG contacts were repositioned in different brain parcellations from the segmentation of patients' anatomical MRI or from templates in the MNI coordinate system. The F-TRACT database using the first pool of 213 patients provided connectivity probability values for 95% of possible intrahemispheric and 56% of interhemispheric connections and CCEP features for 78% of intrahemisheric and 14% of interhemispheric connections. In this report, we show some examples of anatomo-functional connectivity matrices, and associated directional maps. We also indicate how CCEP features, especially latencies, are related to spatial distances, and allow estimating the velocity distribution of neuronal signals at a large scale. Finally, we describe the impact on the estimated connectivity of the stimulation charge and of the contact localization according to the white or gray matter. The most relevant maps for the scientific community are available for download on f-tract. eu (David et al., 2017) and will be regularly updated during the following months with the addition of more data in the F-TRACT database. This will provide an unprecedented knowledge on the dynamical properties of large fiber tracts in human.Peer reviewe