Lorsqu’une représentation accède à la conscience, ce n’est pas simplement une représentation « objective », mais plutôt une interprétation subjective. Cette interprétation reflète la combinaison de nos connaissances sur le monde avec les données de notre environnement. Il est intéressant de comprendre comment ces interprétations se modifient lorsque l’on est confronté à des incohérences entre nos connaissances et les données. Dans cette thèse, nous avons étudié ces incohérences dans l’environnement et dans le comportement des individus.Dans une première série d’études, nous avons étudié l’apprentissage de régularités dans l’environnement ainsi que les relations entre ce processus et la conscience d’accès. La première étude porte sur les réponses cérébrales associées à la détection de régularités auditives chez des patients épileptiques implantés. La seconde porte sur la mise en place de stratégies lorsque l’on est confronté à de fréquents conflits, conscients ou non. Dans une seconde série d’études, nous avons étudié comment les sujets traitent les incohérences dans leur propre comportement, dans le cadre de la théorie de la dissonance cognitive, en utilisant le paradigme du choix libre. Nous avons identifié un rôle crucial de la mémoire grâce à une étude comportementale et une étude en IRM fonctionnelle.Les résultats de ces quatre études sont discutés dans ce manuscrit autour de deux questions clés. Tout d’abord, ces résultats mettent en évidence l’existence de processus utilisant des stimuli conscients, mais qui ne sont pas conscients eux-mêmes. Ensuite, nous discutons pourquoi l’on tend à chercher de la cohérence, dans notre environnement et dans notre comportement. / When we perceive a word, a picture or a sound, we do not access an ‘objective’ representation of them. Rather we gain immediate access to a subjective interpretation. This interpretation reflects the combination of our prior knowledge about the world with data sampled in the environment. An interesting issue is to understand how we deal with inconsistencies between our prior knowledge and the data from the environment. During this PhD, responses to inconsistencies both in the environment and in subjects’ own behavior were explored. The first series of studies address how subjects process regularities in the environment and how these processes relate to conscious access. To do so, two levels of auditory regularities were studied in epileptic patients implanted with intracranial electrodes. In a second experiment, we used a paradigm derived from the Stroop task to test responses to frequent conscious or unconscious conflicts. Behavioral measures and scalp EEG were used to assess changes in subjects’ strategy when processing trials conflicting with current expectations. In the second series of studies, we analyzed how subjects adapt their interpretations when confronted with inconsistencies in their own behavior, using the framework of cognitive dissonance. The implication of explicit memory was tested in a behavioral experiment and in an fMRI study. The results of these four studies are discussed around two main issues. First, these results highlight the existence of processes which rely on conscious stimuli but are not conscious themselves. Second, we examine what could explain our tendency to constantly seek consistency both in the external world and in our own behavior.

Schizophrenia is a neuropsychiatric disorder lying at the extreme of a spectrum of disorders that possibly share a common abnormality in neural connectivity. Efforts to reverse the core cognitive manifestations of schizophrenia using drug treatments have so far been unsuccessful. This thesis investigates the cognitive abnormalities and their electrophysiological correlates across the schizophrenia spectrum in order to identify and validate biomarkers for proof of concept studies of cognitive enhancers. Such studies in milder disorders of the schizophrenia spectrum such as schizotypal personality trait may be a crucial method in identifying new effective compounds, as reviewed in Chapter 3, and tested in Chapter 4. The latter features the results of a large three-centre study which probed the sensitivity of several neuropsychological measures to the schizotypy phenotype, as well as to the effects of amisulpride, risperidone and nicotine. Schizotypal volunteers showed impaired performance only on the more difficult tasks. The most consistent pharmacological finding was that amisulpride tended to improve performance in the high schizotypy group but to impair it in the average schizotypy controls. One interpretation is that the ability of low dose amisulpride to enhance dopamine function in frontal cortex reversed an impairment of dopamine function present in the high schizotypes which is thought to occur in schizophrenia. Chapter 5 explored the methodological question of whether low or average schizotypy individuals should be used as controls in cognitive comparisons versus high schizotypy. The results suggest that low schizotypes have the most intact cognitive performance and are therefore the control group of choice. Chapters 6, 7 and 8 tested the hypothesis that cognitive deficits are part of a larger information processing abnormality in the schizophrenia spectrum. In accordance, both high schizotypy and schizophrenia patients exhibited reduced amplitude of an early visual evoked potential P1 (Chapters 6 and 8, respectively) and disruptions of the underlying evoked neural oscillations (Chapters 7 and 8). The pattern of abnormalities suggested an inefficient top-down modulation of perception in the schizophrenia spectrum. These data argue that cognitive abnormalities and their electrophysiological correlate may be sensitive biomarkers of the core dysconnectivity deficit in schizophrenia. This thesis supports their use in proof of concept studies to foster the development of cognitive enhancers.

The research investigates the dynamic relations between sound, space and the audience perception as related to an artist’s intention. What is the relation between sound and space in the sonic arts, and to what kind of merger does it lead? What relationship exists between the intention of the composer and the perception of the audience regarding architectural and environmental spaces? Is there a common thread of perception of architectural and environmental spaces among participants? Is embodiment a key for the perception of the dynamic relations of sound and space? The framework for the investigation is based on a map of three defined spaces (Real, Virtual, and Hyperbiological) included in a portfolio of six works (three electroacoustic compositions, two sound installations, and one performance), which lead to the analysis of the perception of space, namely, the perception of architectural and environmental spaces as required by the portfolio. The original knowledge resides in the exploration of a potential common representation (space and sound perception being, of course, a personal representation) of internal perceptual spaces and mental imageries generated by the works. The act of listening plays a major role in the development of the portfolio presented and includes Pauline Oliveros’ concept of deep listening (Oliveros 2005). Sound and space are intimately related in the portfolio. One particular element emerging from this relationship is the plastic quality of sound, meaning that sound is considered and observed as a material that is shaped by space. From this perspective the research investigates the ‘sculptural’ and morphological quality of the relationship between sound and space. The results include the specific language and signature of the artworks that delineate the intersection of music and fine arts. The portfolio pays a large tribute to several iconic artists present in the outposts of sound blurred by space. Composers and artists are therefore presented in the theoretical section in order to highlight how their pioneering works have influenced and informed the present research portfolio. The analysis of the perception of the artworks relates to a methodology based on an empirical survey inspired by phenomenology.

Background: Subarachnoid haemorrhage (SAH) is a severe stroke that in 85% of all cases is caused by the rupture of a cerebral aneurysm. The median age at onset is 50-55 years and the overall mortality is approximately 45%.Sufficient cortisol levels are important for survival. After SAH hypothalamic/pituitary blood flow may be hampered this could result in inadequate secretion of cortisol. SAH is also associated with a substantial inflammatory response. Asymmetric dimethyl arginine (ADMA), an endogenous inhibitor of nitric oxide synthase, mediates vasoconstriction and increased ADMA levels may be involved in inflammation and endothelial dysfunction. Continuous electroencephalogram (EEG) monitoring can be used to detect non-convulsive seizures, leading to ischemic insults in sedated SAH patients. Elevated ADMA levels are risk factors for vascular diseases. Vascular disease has been linked to stress, inflammation and endothelial dysfunction. SAH possesses all those clinical features and theoretically SAH could thus induce vascular disease. Aims: 1. Assess cortisol levels after SAH, and evaluate associations between cortisol and clinical parameters. 2. Assess ADMA levels and arginine/ADMA ratios after SAH and evaluate associations between ADMA levels and arginine/ADMA ratios with severity of disease, co-morbidities, sex, age and clinical parameters. 3. Investigate occurrence of subclinical seizures in sedated SAH patients. 4. Evaluate if patients that survive a SAH ≥ one year have an increased risk of vascular causes of death compared to a normal population. Results: Continuous infusion of sedative drugs was the strongest predictor for a low (&lt;200 nmol/L) serum cortisol. The odds ratio for a sedated patient to have a serum cortisol &lt; 200 nmol/L was 18.0 times higher compared to an un-sedated patient (p &lt; 0.001). Compared to admission values, 0-48 hours after SAH, CRP increased significantly already in the time-interval 49-72 hours (p&lt;0.05), peaked in the time-interval 97-120 hours after SAH and thereafter decreased. ADMA started to increase in the time-interval 97-120 hours (p&lt;0.05). ADMA and CRP levels were significantly higher, and arginine/ADMA ratios were significantly lower in patients with a more severe condition (p&lt;0.05). Epileptic seizure activity, in sedated SAH patients, was recorded in 2/28 (7.1%) patients during 5/5468 (0.09%) hours of continuous EEG monitoring. Cerebrovascular disease was significantly more common as a cause of death in patients that had survived a SAH ≥ one year, compared to the population from the same area (p&lt;0.0001). Conclusions: Continuous infusion of sedative drugs was associated with low (&lt;200 nmol/L) cortisol levels. ADMA increased significantly after SAH, after CRP had peaked, indicating that endothelial dysfunction, with ADMA as a marker, is induced by a systemic inflammation. Patients with a more severe condition had significantly higher ADMA and CRP levels, and significantly lower arginine/ADMA ratio. Continuous sedation in sedated SAH patients seems to be beneficial in protecting from subclinical seizures. Cerebrovascular causes of death are more common in SAH survivors. / <p>Funding: The Swedish Society of Medicine, the Faculty of Medicine at Umeå University, The Kempe Foundations and The Stroke Foundation of Northern Sweden supported this study financially.</p>

Fibromyalgia syndrome (FMS) is a disorder characterised by chronic widespread pain, non-restorative sleep, fatigue and daytime dysfunction. Occurring in 2-5% of the population, the aetiology is largely unknown. Sleep dysfunction occurs in over 90% of FMS patients. While research has shown that both the macrostructure and microstructure of sleep may be altered, there remain inconsistencies in the polysomnographic (PSG) findings, and wide variations in methodological approaches. Few studies have controlled for symptom duration or the time elapsed between diagnosis and PSG sleep assessments. In addition, while psychometric analyses have suggested a distinctive FMS psychological profile (which includes higher levels of depressive symptoms, anxiety and fatigue) few studies have simultaneously, and thoroughly examined sleep and psychological status in the same participants. A frequently reported alteration found in the sleep microstructure of FMS patients is the alpha-delta sleep anomaly, characterised by an increase in alpha wave activity during slow wave sleep. Originally considered a possible neurological contribution to FMS, whether the alpha-delta sleep anomaly is fundamental to the development of fibromyalgia syndrome, or results mainly from the pain experience of FMS patients remains unknown. No previous study has directly compared the sleep of FMS and other (non-FMS) patients experiencing similar levels of chronic pain and sleep dysfunction. The present study was designed to examine sleep macrostructure and microstructure in FMS patients, and evaluate the role of the alpha-delta sleep anomaly as either a possible contributor to fibromyalgia syndrome, or a likely consequence of pain experience. In order to explore these relationships, detailed sleep, activity and psychological profiles were compared in 3 groups: 1) FMS patients (n = 19); 2) osteoarthritis patients with sleep disturbance (n = 17); and non-clinical (normal healthy) adults (n = 10). In order to standardise diagnostic reliability and symptom chronicity, the FMS group was recruited from a single rheumatology facility immediately following diagnosis. Guided by a series of formal research questions, analyses compared sleep macrostructure (using American Academy of Sleep Medicine criteria), sleep microstructure (using spectral analysis), and a range of psychological variables (including pain experience, sleepiness, fatigue, depression, anxiety, perceived social support, health locus of control, pain catastrophizing and personality). The results indicated that the alpha-delta sleep anomaly is not unique to FMS, but appears to be a feature found in the sleep of normal healthy adults and (to a greater extent) those with FMS and osteoarthritis. The incidence of the anomaly was statistically similar in both clinical (FMS and osteoarthritis) groups, a pattern consistent of its being a secondary feature of pain, rather than a primary abnormality of FMS. Overall, the psychometric assessments of state and trait anxiety and depression better discriminated between the three groups than did the sleep variables. Nevertheless, on measures of sleep, perceived social support, health locus of control, and pain catastrophizing, FMS and osteoarthritis patients were not significantly different, though both clinical groups differed on these variables from healthy controls.

Certain electrophysiological markers hold promise in distinguishing individuals with major depressive disorder (MDD) and in predicting antidepressant response, thereby assisting with assessment and optimizing treatment, respectively. This thesis examined resting brain activity via electroencephalographic (EEG) recordings, as well as EEG-derived event-related potentials (ERPs) to auditory stimuli and facial expression presentations in individuals with MDD and controls. Additionally, the utility of resting EEG as well as auditory ERPs (AEPs), and the associated loudness-dependence of AEPs (LDAEP) slope, were assessed in predicating outcome to chronic treatment with one of three antidepressant regimens [escitalopram (ESC); bupropion (BUP); ESC+BUP]. Relative to controls, depressed adults had lower pretreatment cortical activity in regions implicated in approach motives/positive processing. Increased anterior cingulate cortex (ACC)-localized theta was observed, possibly reflecting emotion/cognitive regulation disturbances in the disorder. AEPs and LDAEPs, putative indices of serotonin activity (implicated in MDD etiology), were largely unaltered in MDD. Assessment of ERPs to facial expression processing indicated slightly blunted late preconscious perceptual processing of expressions, and prolonged processing of intensely sad faces in MDD. Faces were rated as sadder overall in MDD, indicating a negative processing bias. Treatment responders (vs. non-responders) exhibited baseline cortical hypoactivity; after a week of treatment, cortical arousal emerged in responders. Increased baseline left fronto-cortical activity and early shifts towards this profile were noted in responders (vs. non-responders). Responders exhibited a steep, and non-responders shallow, baseline N1 LDAEP derived from primary auditory cortex activity. P2 LDAEP slopes (primary auditory cortex-derived) increased after a week of treatment in responders and decreased in non-responders. Consistent with overall findings, ESC responders displayed baseline cortical hypoactivity and steep LDAEP-sLORETA slopes (vs. non-responders). BUP responders also exhibited steep baseline slopes and high ACC theta. These results indicate that specific resting brain activity profiles appear to distinguish depressed from non-depressed individuals. Subtle ERP modulations to simple auditory and emotive processing also existed in MDD. Resting alpha power, ACC theta activity and LDAEP slopes predicted antidepressant response in general, but were limited in predicting outcome to a particular treatment, which may be associated with limited sample sizes.

Comment les agents anesthésiques induisent-ils une perte de conscience lors de l’anesthésie générale? La dissection des mécanismes neuronaux de l’anesthésie générale représente un défi important en neurosciences. L’émergence de l’IRM fonctionnelle (IRMf) chez le primate non-humain donne l’occasion d’étudier l’activité neuronale à l’état éveillé et sous anesthésie en s’affranchissant des contraintes cliniques. Le développement récent de paradigmes auditifs, tel que le paradigme ‘local-global’, qui explore spécifiquement les réseaux cérébraux impliqués dans l’état conscient, nous a permis d’émettre l’hypothèse que la combinaison de l’IRMf chez le primate, de paradigmes auditifs et de protocoles d’anesthésie contrôlés par l’électroencéphalogramme (EEG), pourraient aider à disséquer les mécanismes neuronaux de l’anesthésie générale.Dans une première étape, étant donnée l’utilisation extensive de l’IRM dans notre travail, il était important d’étudier systématiquement l’effet des agents anesthésiques sur l’oxygénation vasculaire cérébrale, paramètre critique pour le signal IRMf. Nous avons donc réalisé une expérience préliminaire, faisant appel à l’IRM à ultra-haut champ magnétique chez le rongeur, afin de détecter les éventuels modifications du signal T2* induits par chacun des agents anesthésiques. Nous avons pu démontrer que le propofol et la kétamine, deux agents anesthésiques utilisés en clinique, affectaient moins l’oxygénation sanguine cérébrale que les anesthésiques volatils.Dans une deuxième étape, nous avons développé une « boîte à outils » pour l’IRMf chez le primate éveillé et anesthésié, et avons validé notre dispositif expérimental avec un paradigme auditif basé sur des sons simples (basse et haute fréquence).Dans une troisième étape, nous avons testé le paradigme auditif ‘local-global’ chez le macaque éveillé et avons pu démontrer que le cerveau du macaque est capable d’un codage prédictif hiérarchique à travers un espace de travail global, composé d’un réseau fronto-pariéto-cingulaire, montrant une forte homologie avec celui de l’Homme.Dans une quatrième étape, nous avons testé le paradigme auditif ‘local-global’, chez le macaque anesthésié et avons pu démontrer une désorganisation progressive de l’espace de travail global neuronal sous anesthésie. Cette désorganisation a été proportionnelle au niveau de sédation sous propofol, et complète sous sédation profonde à la kétamine. Ces résultats sont compatibles avec l’hypothèse selon laquelle le mécanisme de la perte de conscience sous anesthésie, est lié à une désorganisation de l’organisation fonctionnelle hiérarchique de l’espace de travail neuronal. Le cortex pariétal apparaît comme une cible commune aux deux agents anesthésiques.Dans la dernière étape, nous avons étudié le réseau cérébral par défaut (« default mode network ») chez le macaque éveillé et anesthésié. Nous avons pu démontrer que sous anesthésie, le cerveau présentait encore des patrons de connectivité distincts et riches, mais que ces patrons étaient fortement liés à l’organisation anatomique sous-jacente, alors que, à l’état éveillé cette organisation se caractérisait par un haut degré de flexibilité temporelle ce qui permet une exploration non-stéréotypée d’une plus grande variété d’états cérébraux.En conclusion, les agents anesthésiques entraînent une désorganisation de l’espace de travail global neuronal, avec pour conséquence l’altération des dynamiques temporelles de l’activité cérébrale spontanée, induisant ainsi une suppression de la conscience. / How can anesthetics induce a loss of consciousness during general anesthesia? A major challenge in neuroscience is to dissect the mechanisms of general anesthesia, which is quite difficult to achieve in the clinical conditions. The dawning of monkey functional MRI (fMRI) in neuroscience is an important opportunity to investigate neuronal activity in awake and anesthetized conditions. The recent development of auditory paradigms, such as the ‘local-global’ paradigm, that specifically explore brain networks thought to be specific of the conscious state led us to hypothesize that the combination of primate fMRI, auditory paradigms and single-drug anesthetic protocols with electroencephalography (EEG) control would help dissect the neuronal mechanisms of general anesthesia. In a first step, because we planned an extensive use of fMRI in our work, it was key to screen anesthetic agents for their effects on brain vascular oxygenation, a critical parameter for fMRI signal. Thus we did a preliminary experiment using ultra-high field MRI in rodents to assess subtle changes of the T2* signal under different anesthetic conditions and could demonstrate that propofol and ketamine, both clinical anesthetics, affects less brain blood oxygenation than volatile agents. In a second step, we developed a toolbox for awake and anesthetized monkey fMRI and validated the experimental set-up with a simple sound paradigm (low and high frequency sounds). In the third step, we tested the ‘local-global’ auditory paradigm in awake monkeys and could demonstrate that the macaque brain was capable of hierarchical predictive coding through a hypothetical macaque Global Neuronal Workspace made of frontal, parietal and cingulate cortices, in a striking homology with humans. In the fourth step, we tested the ‘local-global’ auditory paradigm in anesthetized monkeys and could demonstrate a progressive disorganization of the macaque GNW under anesthesia when increasing the levels of propofol sedation, and a complete suppression of the macaque GNW under deep ketamine sedation. These results are compatible with the hypothesis that the mechanism of loss of consciousness under anesthesia is related to the disorganization of a hierarchical GNW, with the parietal cortex as a common target among anesthetics. In the final step we studied the default network by acquiring resting state in awake and anesthetized monkeys and could demonstrate that under anesthesia, the brain still exhibits distinct and rich connectivity patterns, but these patterns become strongly related to the underlying white-matter structural map in a monotonic manner, while the awake state is characterized by a high degree of temporal flexibility which allows for a non-stereotyped exploration of a greater variety of brain states. In conclusion, by disorganizing the GNW, anesthetics alter the temporal dynamics of spontaneous brain activity, and specifically its departure from mere random fluctuations along established anatomical routes, leading to consciousness suppression.

Ce mémoire de thèse porte sur le traitement et l'analyse des signaux issus des unités de soins intensifs néonatales (USIN) pour l'étude de la maturité, de l'infection généralisée et de l'influence de l'immunisation chez le nouveau-né prématuré. Une attention particulière est portée sur l'électroencéphalographie et le signal de respiration. Pour le premier, ce signal est souvent bruité en USIN et des méthodes de décomposition du signal et d'annulation optimale du bruit, adaptées aux particularités des EEG immatures, ont été proposées et évaluées objectivement sur signaux réels et simulés. L'analyse de l'EEG et des bouffées delta, repérées automatiquement par un classificateur proposé, ont permis d'étudier la maturation et les effets de la vaccination. Pour la seconde modalité, la respiration, des méthodes non-linéaires et fractales sont retenues et adaptées pour évaluer la maturité et l'infection généralisée. Une étude de robustesse des méthodes d'estimation est menée et on montre que l'exposant de Hurst, estimé sur des signaux de variabilité respiratoire, est un bon détecteur de l'infection. / This Ph.D. dissertation processes and analyzes signals from the neonatal intensive care units (NICUs) for the study of maturity, systemic infection (sepsis) and the influence of immunization in the premature newborn. A special attention is payed to the electroencephalography and the breathing signal. The former is often contaminated by several sources of noise, thus methods based on the signals decomposition and optimal noise cancellation, adapted to the characteristics of the immature EEG, were proposed and evaluated objectively on real and simulated signals. By means of the EEG and delta burst analysis, detected automatically by a proposed classifier, infant's maturation and the effects of vaccination are studied. Concerning the second signal, breathing, non-linear and fractal methods are adapted to evaluate maturity and sepsis. A robustness study of estimation methods is also conducted, showing that the Hurst exponent, estimated on respiratory variability signals, is a good detector of infection.

In this thesis we investigate the mechanisms underlying the generation of abnormal EEG rhythms in epilepsy, which is a crucial step towards better treatment of this disorder in the future. To this end, macroscopic scale mathematical models of the interactions between neuronal populations are examined. In particular, the role of interactions between neural masses that are spatially distributed in cortical networks are explored. In addition, two other important aspects of the modelling process are addressed, namely the conversion of macroscopic model variables into EEG output and the comparison of multivariate, spatio-temporal data. For the latter, we adopt a vectorisation of the correlation matrix of windowed data and subsequent comparison of data by vector distance measures. Our modelling studies indicate that excitatory connectivity between neural masses facilitates self-organised dynamics. In particular, we report for the first time the production of complex rhythmic transients and the generation of intermittent periods of 'abnormal' rhythmic activity in two different models of epileptogenic tissue. These models therefore provide novel accounts of the spontaneous, intermittent transition between normal and pathological rhythms in primarily generalised epilepsies and the evocation of complex, self-terminating, spatio-temporal dynamics by brief stimulation in focal epilepsies. Two key properties of these models are excitability at the macroscopic level and the presence of spatial heterogeneities. The identification of neural mass excitability as an important processes in spatially extended brain networks is a step towards uncovering the multi-scale nature of the pathological mechanisms of epilepsy. A direct consequence of this work is therefore that novel experimental investigations are proposed, which in itself is a validation of our modelling approach. In addition, new considerations regarding the nature of dynamical systems as applied to problems of transitions between rhythmic states are proposed and will prompt future investigations of complex transients in spatio-temporal excitable systems.

EEG biofeedback (neurotherapy) has been demonstrated as effective in the treatment of alcoholism, as evidenced by Peniston and Kulkosky's research efforts. These neurotherapy pioneers evaluated the efficacy of alpha-theta brain wave biofeedback as a treatment for chronic alcohol abuse, citing 80% abstinence rates as measured by improvements in psychopathology, serum beta endorphin levels, and long-term alcohol abstinence. Most research with alpha-theta EEG biofeedback has addressed alcohol addiction. Cocaine is now considered to be the most common drug problem of patients entering treatment for drug abuse. To date, only one controlled study has been published that researched alpha-theta neurofeedback in the treatment of "crack" cocaine addiction. The present study was an extension of a 4-year EEG-biofeedback treatment outcome project underway at a faith-based homeless mission in Houston, Texas, with male "crack" cocaine addicts. Changes in personality, attention, and impulsivity were measured following 30 sessions of a non-individualized EEG -biofeedback protocol. Experimental subjects received a variant of the Peniston-Kulkosky alpha-theta protocol for 30 sessions while controls received all elements of the experimental protocol except the EEG biofeedback. Assessment measures included the MMPI-2 and the IVA. Although experimental subjects showed greater mean improvement on most MMPI basic scales and all IVA Attention related measures, results indicated no significant differences between control and experimental groups. The present study did not result in significant differences between control and experimental groups on attentional or personality variables in crack cocaine addicts. Implications and limitations of the study are discussed.