Decoding decisions in healthy subjects and auditory discrimination in comatose patients through single-trial topographic EEG analyses

Neuroimaging studies analyzing neurophysiological signals are typically based on comparing averages of peri-stimulus epochs across experimental conditions. This approach can however be problematic in the case of high-level cognitive tasks, where response variability across trials is expected to be high and in cases where subjects cannot be considered part of a group. The main goal of this thesis has been to address this issue by developing a novel approach for analyzing electroencephalography (EEG) responses at the single-trial level. This approach takes advantage of the spatial distribution of the electric field on the scalp (topography) and exploits repetitions across trials for quantifying the degree of discrimination between experimental conditions through a classification scheme. In the first part of this thesis, I developed and validated this new method (Tzovara et al., 2012a,b). Its general applicability was demonstrated with three separate datasets, two in the visual modality and one in the auditory. This development allowed then to target two new lines of research, one in basic and one in clinical neuroscience, which represent the second and third part of this thesis respectively. For the second part of this thesis (Tzovara et al., 2012c), I employed the developed method for assessing the timing of exploratory decision-making. Using single-trial topographic EEG activity during presentation of a choice's payoff, I could predict the subjects' subsequent decisions. This prediction was due to a topographic difference which appeared on average at ~516ms after the presentation of payoff and was subject-specific. These results exploit for the first time the temporal correlates of individual subjects' decisions and additionally show that the underlying neural generators start differentiating their responses already ~880ms before the button press. Finally, in the third part of this project, I focused on a clinical study with the goal of assessing the degree of intact neural functions in comatose patients. Auditory EEG responses were assessed through a classical mismatch negativity paradigm, during the very early phase of coma, which is currently under-investigated. By taking advantage of the decoding method developed in the first part of the thesis, I could quantify the degree of auditory discrimination at the single patient level (Tzovara et al., in press). Our results showed for the first time that even patients who do not survive the coma can discriminate sounds at the neural level, during the first hours after coma onset. Importantly, an improvement in auditory discrimination during the first 48hours of coma was predictive of awakening and survival, with 100% positive predictive value. - L'analyse des signaux électrophysiologiques en neuroimagerie se base typiquement sur la comparaison des réponses neurophysiologiques à différentes conditions expérimentales qui sont moyennées après plusieurs répétitions d'une tâche. Pourtant, cette approche peut être problématique dans le cas des fonctions cognitives de haut niveau, où la variabilité des réponses entre les essais peut être très élevéeou dans le cas où des sujets individuels ne peuvent pas être considérés comme partie d'un groupe. Le but principal de cette thèse est d'investiguer cette problématique en développant une nouvelle approche pour l'analyse des réponses d'électroencephalographie (EEG) au niveau de chaque essai. Cette approche se base sur la modélisation de la distribution du champ électrique sur le crâne (topographie) et profite des répétitions parmi les essais afin de quantifier, à l'aide d'un schéma de classification, le degré de discrimination entre des conditions expérimentales. Dans la première partie de cette thèse, j'ai développé et validé cette nouvelle méthode (Tzovara et al., 2012a,b). Son applicabilité générale a été démontrée avec trois ensembles de données, deux dans le domaine visuel et un dans l'auditif. Ce développement a permis de cibler deux nouvelles lignes de recherche, la première dans le domaine des neurosciences cognitives et l'autre dans le domaine des neurosciences cliniques, représentant respectivement la deuxième et troisième partie de ce projet. En particulier, pour la partie cognitive, j'ai appliqué cette méthode pour évaluer l'information temporelle de la prise des décisions (Tzovara et al., 2012c). En se basant sur l'activité topographique de l'EEG au niveau de chaque essai pendant la présentation de la récompense liée à un choix, on a pu prédire les décisions suivantes des sujets (en termes d'exploration/exploitation). Cette prédiction s'appuie sur une différence topographique qui apparaît en moyenne ~516ms après la présentation de la récompense. Ces résultats exploitent pour la première fois, les corrélés temporels des décisions au niveau de chaque sujet séparément et montrent que les générateurs neuronaux de ces décisions commencent à différentier leurs réponses déjà depuis ~880ms avant que les sujets appuient sur le bouton. Finalement, pour la dernière partie de ce projet, je me suis focalisée sur une étude Clinique afin d'évaluer le degré des fonctions neuronales intactes chez les patients comateux. Des réponses EEG auditives ont été examinées avec un paradigme classique de mismatch negativity, pendant la phase précoce du coma qui est actuellement sous-investiguée. En utilisant la méthode de décodage développée dans la première partie de la thèse, j'ai pu quantifier le degré de discrimination auditive au niveau de chaque patient (Tzovara et al., in press). Nos résultats montrent pour la première fois que même des patients comateux qui ne vont pas survivre peuvent discriminer des sons au niveau neuronal, lors de la phase aigue du coma. De plus, une amélioration dans la discrimination auditive pendant les premières 48heures du coma a été observée seulement chez des patients qui se sont réveillés par la suite (100% de valeur prédictive pour un réveil).

Anharmonicity contributions to the vibrational second hyperpolarizability of conjugated oligomers

Restricted Hartree-Fock 6-31G calculations of electrical and mechanical anharmonicity contributions to the longitudinal vibrational second hyperpolarizability have been carried out for eight homologous series of conjugated oligomers - polyacetylene, polyyne, polydiacetylene, polybutatriene, polycumulene, polysilane, polymethineimine, and polypyrrole. To draw conclusions about the limiting infinite polymer behavior, chains containing up to 12 heavy atoms along the conjugated backbone were considered. In general, the vibrational hyperpolarizabilities are substantial in comparison with their static electronic counterparts for the dc-Kerr and degenerate four-wave mixing processes (as well as for static fields) but not for electric field-induced second harmonic generation or third harmonic generation. Anharmonicity terms due to nuclear relaxation are important for the dc-Kerr effect (and for the static hyperpolarizability) in the σ-conjugated polymer, polysilane, as well as the nonplanar π systems polymethineimine and polypyrrole. Restricting polypyrrole to be planar, as it is in the crystal phase, causes these anharmonic terms to become negligible. When the same restriction is applied to polymethineimine the effect is reduced but remains quantitatively significant due to the first-order contribution. We conclude that anharmonicity associated with nuclear relaxation can be ignored, for semiquantitative purposes, in planar π-conjugated polymers. The role of zero-point vibrational averaging remains to be evaluated

Nuclear relaxation contribution to static and dynamic (infinite frequency approximation) nonlinear optical properties by means of electrical property expansions: Application to HF, CH4, CF4, and SF6

Electrical property derivative expressions are presented for the nuclear relaxation contribution to static and dynamic (infinite frequency approximation) nonlinear optical properties. For CF4 and SF6, as opposed to HF and CH4, a term that is quadratic in the vibrational anharmonicity (and not previously evaluated for any molecule) makes an important contribution to the static second vibrational hyperpolarizability of CF4 and SF6. A comparison between calculated and experimental values for the difference between the (anisotropic) Kerr effect and electric field induced second-harmonic generation shows that, at the Hartree-Fock level, the nuclear relaxation/infinite frequency approximation gives the correct trend (in the series CH4, CF4, SF6) but is of the order of 50% too small

Early attentional processes distinguish selective from global motor inhibitory control : An electrical neuroimaging study

The rapid stopping of specific parts of movements is frequently required in daily life. Yet, whether selective inhibitory control of movements is mediated by a specific neural pathway or by the combination between a global stopping of all ongoing motor activity followed by the re-initiation of task-relevant movements remains unclear. To address this question, we applied time-wise statistical analyses of the topography, global field power and electrical sources of the event-related potentials to the global vs selective inhibition stimuli presented during a Go/NoGo task. Participants (n = 18) had to respond as fast as possible with their two hands to Go stimuli and to withhold the response from the two hands (global inhibition condition, GNG) or from only one hand (selective inhibition condition, SNG) when specific NoGo stimuli were presented. Behaviorally, we replicated previous evidence for slower response times in the SNG than in the Go condition. Electrophysiologically, there were two distinct phases of event-related potentials modulations between the GNG and the SNG conditions. At 110âeuro"150 ms post-stimulus onset, there was a difference in the strength of the electric field without concomitant topographic modulation, indicating the differential engagement of statistically indistinguishable configurations of neural generators for selective and global inhibitory control. At 150âeuro"200 ms, there was topographic modulation, indicating the engagement of distinct brain networks. Source estimations localized these effects within bilateral temporo-parieto-occipital and within parieto-central networks, respectively. Our results suggest that while both types of motor inhibitory control depend on global stopping mechanisms, selective and global inhibition still differ quantitatively at early attention-related processing phases.

Systematic study of the static electrical properties of the CO molecule: influence of the basis set size and correlation energy

The influence of the basis set size and the correlation energy in the static electrical properties of the CO molecule is assessed. In particular, we have studied both the nuclear relaxation and the vibrational contributions to the static molecular electrical properties, the vibrational Stark effect (VSE) and the vibrational intensity effect (VIE). From a mathematical point of view, when a static and uniform electric field is applied to a molecule, the energy of this system can be expressed in terms of a double power series with respect to the bond length and to the field strength. From the power series expansion of the potential energy, field-dependent expressions for the equilibrium geometry, for the potential energy and for the force constant are obtained. The nuclear relaxation and vibrational contributions to the molecular electrical properties are analyzed in terms of the derivatives of the electronic molecular properties. In general, the results presented show that accurate inclusion of the correlation energy and large basis sets are needed to calculate the molecular electrical properties and their derivatives with respect to either nuclear displacements or/and field strength. With respect to experimental data, the calculated power series coefficients are overestimated by the SCF, CISD, and QCISD methods. On the contrary, perturbation methods (MP2 and MP4) tend to underestimate them. In average and using the 6-311 + G(3df) basis set and for the CO molecule, the nuclear relaxation and the vibrational contributions to the molecular electrical properties amount to 11.7%, 3.3%, and 69.7% of the purely electronic μ, α, and β values, respectively

Microscopic and macroscopic polarization within a combined quantum mechanics and molecular mechanics model

A polarizable quantum mechanics and molecular mechanics model has been extended to account for the difference between the macroscopic electric field and the actual electric field felt by the solute molecule. This enables the calculation of effective microscopic properties which can be related to macroscopic susceptibilities directly comparable with experimental results. By seperating the discrete local field into two distinct contribution we define two different microscopic properties, the so-called solute and effective properties. The solute properties account for the pure solvent effects, i.e., effects even when the macroscopic electric field is zero, and the effective properties account for both the pure solvent effects and the effect from the induced dipoles in the solvent due to the macroscopic electric field. We present results for the linear and nonlinear polarizabilities of water and acetonitrile both in the gas phase and in the liquid phase. For all the properties we find that the pure solvent effect increases the properties whereas the induced electric field decreases the properties. Furthermore, we present results for the refractive index, third-harmonic generation (THG), and electric field induced second-harmonic generation (EFISH) for liquid water and acetonitrile. We find in general good agreement between the calculated and experimental results for the refractive index and the THG susceptibility. For the EFISH susceptibility, however, the difference between experiment and theory is larger since the orientational effect arising from the static electric field is not accurately described

Calculation of radio electrical coverage in Medium-Wave Frequencies

The aim of this project is to accomplish an application software based on Matlab to calculate the radioelectrical coverage by surface wave of broadcast radiostations in the band of Medium Wave (WM) all around the world. Also, given the location of a transmitting and a receiving station, the software should be able to calculate the electric field that the receiver should receive at that specific site. In case of several transmitters, the program should search for the existence of Inter-Symbol Interference, and calculate the field strenght accordingly. The application should ask for the configuration parameters of the transmitter radiostation within a Graphical User Interface (GUI), and bring back the resulting coverage above a map of the area under study. For the development of this project, it has been used several conductivity databases of different countries, and a high-resolution elevation database (GLOBE). Also, to calculate the field strenght due to groundwave propagation, it has been used ITU GRWAVE program, which must be integrated into a Matlab interface to be used by the application developed.

Design of electron band pass filters for electrically biased finite superlattices

We design optimal band pass filters for electrons in semiconductor heterostructures, under a uniform applied electric field. The inner cells are chosen to provide a desired transmission window. The outer cells are then designed to transform purely incoming or outgoing waves into Bloch states of the inner cells. The transfer matrix is interpreted as a conformal mapping in the complex plane, which allows us to write constraints on the outer cell parameters, from which physically useful values can be obtained.

Spin-orbit effects in GaAs quantum wells: Interplay between Rashba, Dresselhaus, and Zeeman interactions

The interplay between Rashba, Dresselhaus, and Zeeman interactions in a quantum well submitted to an external magnetic field is studied by means of an accurate analytical solution of the Hamiltonian, including electron-electron interactions in a sum-rule approach. This solution allows us to discuss the influence of the spin-orbit coupling on some relevant quantities that have been measured in inelastic light scattering and electron-spin resonance experiments on quantum wells. In particular, we have evaluated the spin-orbit contribution to the spin splitting of the Landau levels and to the splitting of charge- and spin-density excitations. We also discuss how the spin-orbit effects change if the applied magnetic field is tilted with respect to the direction perpendicular to the quantum well.

Spin-orbit effects in GaAs quantum wells: Interplay between Rashba, Dresselhaus, and Zeeman interactions

The interplay between Rashba, Dresselhaus, and Zeeman interactions in a quantum well submitted to an external magnetic field is studied by means of an accurate analytical solution of the Hamiltonian, including electron-electron interactions in a sum-rule approach. This solution allows us to discuss the influence of the spin-orbit coupling on some relevant quantities that have been measured in inelastic light scattering and electron-spin resonance experiments on quantum wells. In particular, we have evaluated the spin-orbit contribution to the spin splitting of the Landau levels and to the splitting of charge- and spin-density excitations. We also discuss how the spin-orbit effects change if the applied magnetic field is tilted with respect to the direction perpendicular to the quantum well.

The epithelial sodium channel mediates the directionality of galvanotaxis in human keratinocytes.

Cellular directional migration in an electric field (galvanotaxis) is one of the mechanisms guiding cell movement in embryogenesis and in skin epidermal repair. The epithelial sodium channel (ENaC), in addition to its function of regulating sodium transport in kidney, has recently been found to modulate cell locomotory speed. Here we tested whether ENaC has an additional function of mediating the directional migration of galvanotaxis in keratinocytes. Genetic depletion of ENaC completely blocks only galvanotaxis and does not decrease migration speed. Overexpression of ENaC is sufficient to drive galvanotaxis in otherwise unresponsive cells. Pharmacologic blockade or maintenance of the open state of ENaC also decreases or increases, respectively, galvanotaxis, suggesting that the channel open state is responsible for the response. Stable lamellipodial extensions formed at the cathodal sides of wild-type cells at the start of galvanotaxis; these were absent in the ENaC knockout keratinocytes, suggesting that ENaC mediates galvanotaxis by generating stable lamellipodia that steer cell migration. We provide evidence that ENaC is required for directional migration of keratinocytes in an electric field, supporting a role for ENaC in skin wound healing.

Simulations of electrophoretic collisions of DNA knots with gel obstacles

Gel electrophoresis can be used to separate nicked circular DNA molecules of equal length but forming different knot types. At low electric fields, complex knots drift faster than simpler knots. However, at high electric field the opposite is the case and simpler knots migrate faster than more complex knots. Using Monte Carlo simulations we investigate the reasons of this reversal of relative order of electrophoretic mobility of DNA molecules forming different knot types. We observe that at high electric fields the simulated knotted molecules tend to hang over the gel fibres and require passing over a substantial energy barrier to slip over the impeding gel fibre. At low electric field the interactions of drifting molecules with the gel fibres are weak and there are no significant energy barriers that oppose the detachment of knotted molecules from transverse gel fibres.

Black diholes

We present and analyze exact solutions of the Einstein-Maxwell and Einstein-Maxwell-dilaton equations that describe static pairs of oppositely charged extremal black holes, i.e., black diholes. The holes are suspended in equilibrium in an external magnetic field, or held apart by cosmic strings. We comment as well on the relation of these solutions to brane-antibrane configurations in string and M theory.

Neuronal nitric oxide synthase does not contribute to the modulation of pulmonary vascular tone in fetal lambs with congenital diaphragmatic hernia (nNOS in CDH lambs).

AIM: The aim of this study was to determine the presence of the neuronal nitric oxide synthase (nNOS) in near full-term lambs with congenital diaphragmatic hernia (CDH) and its role in the modulation of pulmonary vascular basal tone. METHODS: We surgically created diaphragmatic hernia on the 85th day of gestation. On the 135th, catheters were used to measure pulmonary pressure and blood flow. We tested the effects of 7-nitroindazole (7-NINA), a specific nNOS antagonist and of N-nitro-L-arginine (L-NNA), a nonspecific nitric oxide synthase antagonist. In vitro, we tested the effects of the same drugs on isolated pulmonary vessels. The presence of nNOS protein in the lungs was detected by Western blot analysis. RESULTS: Neither 7-NINA nor L-NNA modified pulmonary vascular basal tone in vivo. After L-NNA injection, acetylcholine (ACh) did not decrease significantly pulmonary vascular resistance (PVR). In vitro, L-NNA increased the cholinergic contractile-response elicited by electric field stimulation (EFS) of vascular rings from lambs with diaphragmatic hernia. CONCLUSION: We conclude that nNOS protein is present in the lungs and pulmonary artery of near full-term lamb fetuses with diaphragmatic hernia, but that it does not contribute to the reduction of pulmonary vascular tone at birth

Structural and magnetic characterization of the lithiated iron oxide LixFe3O4

The Rietveld profile‐analysis method is used to investigate the x‐ray diffraction pattern of lithiated Fe3O4. It is shown that, after exposure to air, pure magnetite coexists with a lithium‐inserted LixFe3O4 phase. The Mössbauer spectra at 300 and 4.2 K have been used to estimate the lithium content of the sample, the pure magnetite concentration, and the iron distribution over the available 16c and 16d sites of the spinel structure. Magnetization measurements from 4.2 to 120 K with an external magnetic field up to 150 kOe have been used to obtain the saturation magnetic moment, the magnetic anisotropy constants, and the susceptibility. It is concluded that a noncollinear spin structure should be present in Li0.5Fe3O4. These results indicate that there is no room‐temperature extrusion of iron even for x→2.0, but that on exposure to air LixFe3O4 samples with x>0.5 are oxidized at room temperature by delithiation.