Modeling of brain activity is often seen as requiring great computing power. However in the special case of modeling scalp EEG it is possible to adopt a continuum approximation for the cortex, and then to use the techniques of wave physics to describe its consequent large-scale dynamics. The model incorporates the following critical components: two classes of neurons (excitatory and inhibitory), the typical number and strength of connections between these two classes, the corresponding connections within the thalamus and between the thalamus and cortex, the time constants and basic physiology of neurons, and the propagation of activity between neurons. Representing the immense intricacy of brain anatomy and physiology with suitable summary equations and average parameter values has meant that the model is able to capture the essential characteristics of EEG and ERPs, and to do so in a computationally manageable way.

Etude des signaux électrophysiologiques intra-cérébraux et imagerie de sources électriques appliquées aux interactions entre les épilepsies et la cognition

Discrepant findings on whether children with autism display response inhibition deficits may be partially due to the wide variety of behavioral tasks used to assess inhibition. A more useful way of understanding early cognitive/attentional processes that influence response inhibition may be to look at neurophysiological measures. Specifically, the event related potential N2, a measurement of cognitive control or the effortful decision to inhibit a prepotent behavioral response, may be useful in understanding the discrepancy in response inhibition. In the current study we measured the N2 as high-functioning autistic children and age, IQ-matched control children performed a modified Flanker task. We further examined the associations between N2 amplitude and latency and variations in social communication within the HFA sample. Behavioral and electrophysiological data from a modified Flanker task were collected from 27 HFA (1 female) and 24 typically developing controls (1 female) ranging in age from 8- to 16-years. Symptom severity was measured using the ASSQ, ADI, and SCQ. Regarding behavioral performance, HFA children committed more errors than control children when controlling for age and verbal IQ. Electrophysiological performance indicated marginal group differences in N2 amplitude when controlling for age. Typical age-related decline in N2 amplitude was observed in the control group but not in the HFA group. There were no significant group differences found for N2 latency. In addition, greater N2 amplitude was correlated with lower scores on the SCQ for the HFA children. Behavioral performance does not conclude that the HFA children show deficits in inhibition, but deficits regarding impulsivity. Electrophysiological data suggest developmental change in N2 amplitude differentiates the HFA and control groups. Finally, the relationship between larger N2 amplitude and lower scores on the SCQ, within the HFA children, indicate that social communication deficits are less when greater cognitive effort is utilized.

Although a lot of information is available from our environment at every moment, only a small part gives rise to a conscious percept. It is then legitimate to wonder which mechanisms are involved in the perception phenomenon. On the basis of which processes will a sensory stimulation be perceived consciously? What happens to the stimulations that are not consciously perceived? The work presented in this thesis aims to bring some elements of response to these two questions in the auditory modality. Through different behavioral and electroencephalographic studies, we suggest that knowledge could have a top-down facilitatory influence on high-level as well as on low-level (like detection) processing of complex auditory stimulations. The stimulations we have some knowledge about (phonologic or semantic) are more easily detected than the stimulations that contain neither phonologic nor semantic information. We also show that the activation of the knowledge influences the perception of subsequent stimulations, even when the context is not perceived consciously. This is evidenced by a subliminal semantic priming effect and by modifications of the neural oscillations in the beta frequency band associated with lexical processing of stimulations that were not consciously categorized. Hence, auditory perception can be considered as the product of the continuous interaction between the context set by the environment and the knowledge one has about specific stimuli. Such an interaction would lead listeners to preferentially perceive what they already know. / Tandis que de nombreuses informations sont disponibles dans notre environnement à chaque instant, toutes ne donnent pas lieu à une perception consciente. Il est alors légitime de se demander quels mécanismes entrent en jeu dans le phénomène de perception. Sur la base de quels processus une stimulation sensorielle sera-t-elle perçue de façon consciente ? Que deviennent les stimulations qui ne sont pas perçues consciemment ? Ce présent travail de thèse vise à apporter des éléments de réponse à ces deux questions dans la modalité auditive. À travers plusieurs études utilisant des approches comportementales mais aussi électroencéphalographiques, nous suggérons que les connaissances pourraient exercer une influence top-down facilitant les hauts comme les bas niveaux de traitement (comme la détection) des stimulations auditives complexes. Les stimulations pour lesquelles nous avons des connaissances (phonologiques et sémantiques) sont mieux détectées que les stimulations ne contenant ni caractéristique phonologique ni caractéristique sémantique. Nous montrons également que l'activation des connaissances influence la perception des stimulations ultérieures, et ce, même lorsque le contexte n'est pas perçu consciemment. En effet nous avons pu mettre en évidence un effet d'amorçage sémantique subliminal et nous avons observé des modifications neuronales oscillatoires dans la bande de fréquence bêta concomitante au traitement lexical de stimulations non catégorisées consciemment. L'ensemble des perceptions auditives ne serait alors que le produit d'une interaction permanente entre le contexte environnemental et les connaissances, ce qui nous conduirait à percevoir préférentiellement ce que nous connaissons déjà.

Intractable epilepsy remains one of the top issues affecting the quality of living in Rett children. While several MeCP2-deficient mouse models of Rett Syndrome have been established, minimal information exists on how the loss of MeCP2 affects brain network activity. To address this issue, in vivo recordings of the hippocampus and somatosensory cortex of MeCP2-deficient mice were taken during exploration, immobility, and sleep. The frequency of hippocampal theta oscillations was significantly attenuated in MeCP2-deficient mice during exploration. A subset of MeCP2-heterozygotes displayed spontaneous, cortical epileptiform-like discharges in the immobile-awake state. Similar epileptiform-like discharges were observed in one of the four Mecp2-null mice recorded. Aside from these EEG abnormalities, basal network activity was preserved. Further, convulsive seizures were not seen. Collectively, these findings indicate that a deficiency of MeCP2 in mice leads to only subtle alterations in brain wave activity, contrasting the severely abnormal EEG observed in Rett girls.

Methyl-CpG-binding proteins (MeCP2, MBD1-MBD3) recruit transcriptional co-repressor molecules to methylated regions and silence transcription. The role of MBD2 in regulating brain function and behavior remains largely unexamined. To begin elucidating whether MBD2 influences neural function, I assessed the behavioral performance of Mbd2 null mice, compared their hippocampal electroencephalographic activity during exploration, and performed protein and mRNA expression assessments. The results indicate that mutant mice display a heightened anxiety-like behavior, diminished explorative activity and reduced sociability compared to wild-type mice. However, these behavioral differences were not paralleled by neurophysiological impairments. Mutant hippocampal and cortical samples display significantly elevated MeCP2 mRNA levels. Yet, MeCP2 protein expression did not mirror the mRNA profile and instead was significantly reduced. Glucocorticoid Receptor mRNA levels were significantly reduced in the hippocampus and cortex regions of Mbd2 null brains. The loss of MBD2 is sufficient to induce behavioral impairments in mice without introducing gross deficits in hippocampal neurophysiology.

Intractable epilepsy remains one of the top issues affecting the quality of living in Rett children. While several MeCP2-deficient mouse models of Rett Syndrome have been established, minimal information exists on how the loss of MeCP2 affects brain network activity. To address this issue, in vivo recordings of the hippocampus and somatosensory cortex of MeCP2-deficient mice were taken during exploration, immobility, and sleep. The frequency of hippocampal theta oscillations was significantly attenuated in MeCP2-deficient mice during exploration. A subset of MeCP2-heterozygotes displayed spontaneous, cortical epileptiform-like discharges in the immobile-awake state. Similar epileptiform-like discharges were observed in one of the four Mecp2-null mice recorded. Aside from these EEG abnormalities, basal network activity was preserved. Further, convulsive seizures were not seen. Collectively, these findings indicate that a deficiency of MeCP2 in mice leads to only subtle alterations in brain wave activity, contrasting the severely abnormal EEG observed in Rett girls.

Methyl-CpG-binding proteins (MeCP2, MBD1-MBD3) recruit transcriptional co-repressor molecules to methylated regions and silence transcription. The role of MBD2 in regulating brain function and behavior remains largely unexamined. To begin elucidating whether MBD2 influences neural function, I assessed the behavioral performance of Mbd2 null mice, compared their hippocampal electroencephalographic activity during exploration, and performed protein and mRNA expression assessments. The results indicate that mutant mice display a heightened anxiety-like behavior, diminished explorative activity and reduced sociability compared to wild-type mice. However, these behavioral differences were not paralleled by neurophysiological impairments. Mutant hippocampal and cortical samples display significantly elevated MeCP2 mRNA levels. Yet, MeCP2 protein expression did not mirror the mRNA profile and instead was significantly reduced. Glucocorticoid Receptor mRNA levels were significantly reduced in the hippocampus and cortex regions of Mbd2 null brains. The loss of MBD2 is sufficient to induce behavioral impairments in mice without introducing gross deficits in hippocampal neurophysiology.

Los objetivos de la tesis han sido: 1.-analizar la aportación al diagnóstico de los registros video-electroencefalográficos (VEEG) ictales obtenidos en régimen ambulatorio y 2.- analizar los factores que intervinieron en la concordancia entre la entrevista clínica y el VEEG. Se estudian 42 VEEG ictales obtenidos desde marzo del 2000 hasta septiembre del 2005, de aquellos pacientes en los que previamente se había efectuado una entrevista clínica sistematizada. Se obtuvo de forma protocolizada datos referentes a la semiología de las crisis, al informador, a los antecedentes patológicos y familiares del paciente, a su exploración clínica, a los resultados del EEG intercrítico y de las pruebas de neuroimagen. El diagnóstico del tipo de crisis, tipo de crisis epiléptica y síndrome epiléptico se realizó dos veces, en primer lugar en base a los datos obtenidos en la entrevista clínica, EEG intercrítico y la neuroimagen, y en segundo lugar el que se efectuó tras el VEEG. La interpretación de los registros VEEG se realizó de forma independiente por 2 expertos, uno de los cuales desconocía los resultados de los datos obtenidos en la entrevista clínica. CONCLUSIONES:1- Uno de cada tres eventos paroxísticos catalogados tras la entrevista clínica de crisis epilépticas no son crisis epilépticas. 2- Un 20% de las crisis inicialmente catalogadas de epilépticas no pudieron ser enmarcadas en un tipo de crisis epiléptica o en un síndrome epiléptico concreto. De éstas el 75% no eran crisis epilépticas. 3- En la entrevista clínica la posibilidad de interrogar a un testigo presencial es un factor determinante en el diagnóstico del tipo de crisis. El diagnóstico fue correcto en el 82% de los casos, cuando la información la aporta un testigo y en el 40% de los casos cuando la aporta sólo el paciente. 4- En nuestra serie, el EEG intercrítico tiene una buena validez para el diagnóstico de epilepsia, con un valor predictivo positivo del 92,5% y un valor predictivo negativo del 80%. / The aim of this study has been : 1-To analyse the usefulness of ambulatory video-EEG monitoring (VEEG) on diagnosis of paroxysmal events. 2-To analyse which factors are determinant to obtain the same diagnosis results after clinical interview and VEEG. 42 ictal video-EEG were recorded from March 2000 to September 2005. Detailed and standardized clinical history had been previously recorded in all subjects. Protocolized data regarding semiology of seizures, informants (patients or witness), patient's phatological background and his familial history, physical examinations, interictal EEG and neuroimaging studies were obtained. Diagnosis of paroxysmal event (epilectic seizure, syncope, psychogenic nonepileptic seizure,.) classification of epileptic seizures and classification of epilepsia was recorded twice, first from findings in clinical interview, interictal EEG and neuroimaging and in second place form VEEG test. VEEG registers were analysed separately by two different experts, one of them without knowing the results obtained in clinical interview. CONCLUSIONS1- One out of three paroxysmal events classified after clinical interview as epileptic seizures were not such epileptic seizures. 2- 20% of paroxysmal events diagnosticated as epileptic seizures after clinical interview, were considered as unclassified epileptic seizures and couldn't be classified into any specific epileptic syndrome. 75% of these were not epileptic seizures.3- Having the opportunity of interrogating witness during the clinical interview, becomes decisive to establish the diagnosis of paroxysmal events. A correct diagnosis was established in 82% of studied paroxysmal events when information was provided by a witness and in 40% when this was provided only by a patient. 4- In our study interictal EEG is of great significance to achieve diagnosis of epilepsia, with a positive predictive value of 92,5% and a negative predictive value of 80%.

El electroencefalograma (EEG) registra la actividad eléctrica del córtex cerebral y su trazado cambia reflejando el efecto de los anestésicos. El límite espectral 95% (LE95%) extraído del EEG mediante análisis espectral, ha sido ampliamente empleado para cuantificar el efecto de fármacos anestésicos (opiáceos e hipnóticos) de forma empírica. El Indice Biespectral linear (L-Bis) obtenido a partir de la aplicación de análisis biespectral y espectral, ha sido empleado también en la cuantificación del efecto de fármacos anestésicos. El parámetro canónico univariante de los opiáceos (PCUopi) ha sido obtenido mediante Correlación Canónica Semilinear para extraer de la señal del EEG la información referente al efecto cortical de los opiáceos. El objetivo de este trabajo es comparar la eficacia del PCUopi como cuantificador del efecto de opiáceos (fentanilo, alfentanilo, sufentanilo, trefentanilo y remifentanilo) e hipnóticos (propofol) sobre el EEG.El registro EEG recogido en diversos estudios previamente realizados, fue digitalizado y analizado de nuevo. Se calculó el PCUopi y el LE95% para cada individuo en cada fármaco opiáceo. Se calculó el PCUopi y el L-Bis para cada individuo en el grupo propofol. Se valoró la capacidad de cada parámetro para extraer del trazado del EEG la información relevante respecto al efecto farmacológico, mediante la comparación del valor de R2 (relación señal-ruido) obtenido con cada parámetro en cada individuo. En segundo lugar se valoró la capacidad de cada parámetro para ser usado como indicador farmacodinámico mediante la estimación de los parámetros farmacodinámicos para cada fármaco estudiado. Finalmente se valoró a priori la capacidad del PCUopi para ser empleado en la clínica en pacientes reales, realizándose para ello simulaciones del curso temporal del efecto farmacológico de cada uno de los opiáceos y del propofol.El PCUopi presentó valores superiores de R2 al LE95% de forma global para todos los opiáceos y de forma individual para todos menos para el sufentanilo. El L-Bis presentó valores de R2 superiores al PCUopi en el caso del propofol. Se estimaron los parámetros farmacodinámicos ke0, C50 y alfa. En base a ello alfentanilo y remifentanilo son los opiáceos con inicio del efecto más rápido tras un bolus,seguidos de trefentanilo, fentanilo y sufentanilo. De acuerdo a sus valores de C50 sufentanilo, fentanilo, remifentanilo, trefentanilo y alfentanilo sería el orden de mayor a menor potencia farmacológica. La desaparición del efecto tras la administración de un bolus es más rápida para remifentanilo, seguido de alfentanilo, trefentanilo, fentanilo y sufentanilo.Empleando un modelo sigmoidal de efecto máximo, el efecto electroencefalográfico del propofol medido con el L-Bis, alcanza su punto máximo aproximadamente 3.75 minutos tras la administración de un bolus. La desaparición del efecto tras una infusión continua es rápida, con una vida media sensible al contexto de alrededor de 5 minutos incluso tras infusiones de duración superior a las 3 horas.Otras simulaciones en las que se ha valorado la evolución del PCUopi en diferentes situaciones clínicas demuestran que a las concentraciones de opiáceo empleadas habitualmente en clínica, los cambios esperados en el PCUopi son mínimos. El PCUopi cambia de forma significativa si las concentraciones de opiáceo son elevadas, en un rango que no se emplea habitualmente en clínica. La presencia de propofol a concentraciones habituales, induce cambios significativos y evidentes en el PCUopi lo que hace pensar que se trata de un parámetro sensible pero poco específico para el efecto de los opiáceos en el entorno clínico.PCUopi permite cuantificar el efecto de los opiáceos y del propofol sobre el EEG. El PCUopi es un descriptor óptimo del efecto de los opiáceos sobre el EEG, estadísticamente superior en su efectividad al LE95%. El L-Bis es un descriptor del efecto electroencefalográfico del propofol superior en eficacia al PCUopi. La integración de modelos farmacocinéticos y farmacodinámicos basados en el EEG como variable subrogada del efecto de opiáceos y propofol permite extraer conclusiones sobre su perfil de uso en clínica.