Nous n’avons pas conscience de l’ensemble des processus réalisés par notre cerveau à chaque instant. Cette dissociation entre l’expérience subjective et l’activité neuronale présente un défi majeur à la fois pour les neurosciences fondamentales, mais également pour la pratique clinique. En effet, non seulement les mécanismes neuronaux de la prise de conscience sont mal compris, mais il reste extrêmement difficile de déterminer si des patients en état végétatif – éveillés mais non-communicants – perçoivent leur environnement consciemment. Ces questions théorique et clinique constituent les deux axes principaux de cette thèse. Dans un premier temps, je développe, à partir des récentes avancées aussi bien empiriques que théoriques, une série d’outils permettant de caractériser les mécanismes neuronaux et computationnels de la perception consciente. En particulier, je montre dans une première étude comment les analyses de classification multivariée permettent de décoder les signaux magnéto- et électro-encéphalographiques à l’échelle de l’essai unique. De plus, dans trois études successives, je propose de nouvelles méthodes de traitement du signal permettant de i) caractériser la structure dynamique des processus évoqués par une stimulation sensorielle ii) de quantifier la quantité d’information échangées entre différentes régions corticales et iii) d’estimer la complexité des réponses cérébrales. Enfin, je montre comment un modèle mathématique utilisant les principes d’inférence bayésienne permet de rendre compte d’un grand nombre de résultats observés dans les études de la perception consciente et inconsciente. Dans un second temps, j’applique ces méthodes aux EEG d’une large cohorte de patients végétatifs, minimalement conscients et conscients. Les résultats montrent que les patients végétatifs présentent i) une altération des réponses corticales tardives évoquées par une stimulation auditive, ii) une diminution de l’échange d’information entre régions cérébrales, iii) des rythmes EEG moyens et lents (< 13Hz) anormaux et iv) une réduction de la complexité de l’activité EEG. A l’avenir, ces différentes signatures neurales de la conscience pourraient être utilisées en synergie pour décoder le contenu conscient et aider au diagnostic, au pronostic et au monitoring des patients non-communicants. / We are not aware of everything our brain does. This dissociation between subjective experience and objective neural activity challenges both theoretical neuroscience and clinical practice. Indeed, not only are the neuronal mechanisms of conscious perception poorly understood, but it remains extremely difficult to deter-mine whether vegetative state patients – who are thus awake but non-communicating – perceive their envi-ronment consciously. These theoretical and clinical questions constitute the two main axes of this thesis. In a first part, I develop, from the recent empirical and theoretical advances, a series of methods to characterize the neural and computational mechanisms of conscious perception. In particular, I show in a first study how multivariate pattern classifiers can decode magneto- and electroencephalographic recordings at the single trial level. In three successive studies, I then propose new signal processing methods to i) characterize the dynamical structure of stimulus-evoked processes ii) quantify the amount of information exchanged across cortical regions and iii) estimate the complexity of cerebral responses. At last, I show how a mathematical model based on Bayesian inference principles, can account for a large number of empirical findings observed in studies of conscious and unconscious perception. In a second part, I apply these methods on EEG recordings acquired from a large cohort of vegetative, minimally conscious and conscious patients. The results show that vegetative state patients present i) impaired late and sustained sound-evoked brain responses, ii) a reduction of the exchange of information across cortical regions iii) abnormal slow and medium EEG rhythms (<13Hz) and iv) a decrease of the EEG complexity. Ultimately, these various neural signatures of consciousness could be used in synergy to decode conscious contents and help to diagnose, predict and monitor the state of consciousness of non-communicating patients.

The traditional diagnosis of patients with disorders of consciousness relies solely on behavioral responses. In 1996 it was estimated that 43% of patients diagnosed with unresponsive wakefulness syndrome (vegetative state) receive the wrong diagnosis. Assessing consciousness is perhaps the most crucial part of the diagnostic process. The challenging task of identifying covert consciousness in this patient group seems to be the biggest issue. In 2006 willful modulation of brain activity in response to a mental imagery task was discovered in a patient with unresponsive wakefulness syndrome. The brain activity was measured with functional magnetic resonance imaging. It was concluded that consciousness was preserved in this patient and new research investigating this novel method began to take place. The aim of this thesis was to conduct a systematic review of the literature and thereby arrive at the best current estimate of the proportion of patients who receive a diagnosis that wrongfully defines them as “unconscious” although they in fact are “covertly conscious”. In this review, 11 studies were examined. The results showed that patients with unresponsive wakefulness syndrome, who still receive the wrong diagnosis, decreased to 22-28% by the use of neuroimaging. This improvement points to the possible use of neuroimaging methods in the diagnosis of disorders of consciousness. However, this result cannot be taken without reservations. The limitations of the studies have to be taken into consideration. For example, most studies included a limited sample size and healthy controls did not always give the expected response to mental imagery tasks.

<p>The accurate diagnosis of disorders of consciousness presents substantial difficulty because of the reliance on behaviour-based assessment tools. A patient may be covertly aware but unable to indicate their state due to physical impairments. Neuroimaging researchers have begun to seek alternate methods of assessment that rely on brain responses rather than behavioural ones. To this end, mental imagery has been employed as a voluntary cognitive activity that can be measured with fMRI or EEG to indicate awareness. In this dissertation I examine the advantages and limitations of these two imaging techniques and argue that EEG is more suitable for this patient population. I expand upon existing mental imagery research by exploring additional tasks that have not been applied to this problem, in order to address three previously unanswered questions that are central to the development of imagery-based diagnostic tools. First, do individuals differ on which imagery tasks produce the most reliable activation? Second, can the robustness of brain activation during imagery be predicted from familiarity with the imagined activity? Third, do fMRI and EEG provide converging evidence about individual imagery performance? In order to answer these questions, 6 mental imagery tasks were examined using simultaneous EEG and fMRI recordings, in combination with participant ratings. The findings revealed that, of the mental imagery tasks studied, mental arithmetic consistently produced the most robust activation at the single subject level. Additionally, there was no relationship between participants’ familiarity with an activity and the level of brain activation during performance. The key finding demonstrated that EEG and fMRI were in agreement on both of these questions, lending support to the increasing use of EEG over fMRI in disorders of consciousness.</p> / Doctor of Philosophy (PhD)

Zielsetzung: Der Nachweis eines Apallischen Syndroms (APS) ist trotz der diagnostischen Kriterien der Multi Society Task Force on persistent vegetative state (MSTF) selbst für erfahrene Kliniker eine diagnostische Herausforderung. Das Ziel der vorliegenden Arbeit ist, inwieweit etablierte neurologische Untersuchungstechniken die Anwendung der MSTF-Kriterien vereinfachen und so zur Diagnose des APS beitragen. Design: Prospektive diagnostische Studie Patienten: Von initial 24 Patienten mit der Differentialdiagnose eines APS wurden 16 Patienten endgültig in die Studie eingeschlossen und einer prospektiven klinischen Untersuchung unterzogen. Das Studienprotokoll umfasste die Untersuchung der spontanen Motorik sowie Reiz korrelierter motorischen Reaktionen, der Primitivreflexe, Habituation und der Okulomotorik. Ergebnisse: Die Diagnosekriterien der MSTF waren bei allen Patienten nachweisbar, die in die Studie eingeschlossenen wurden. Darüber hinaus wurde durch die Studie weitere, ebenfalls häufig auftretende klinischen Symptome identifiziert, die als Markersymptom für eine APS bewertet wurden: spontane Automatismen (N=12), periodisch-alternierende Augenbewegungen (N=12), startle Reaktion nach externer Reizung (N=10) und Spastik (N=9). Klinische Symptome, die erhaltene Bewusstseinsleistung voraussetzen wie reflektorische Sakkaden, Habituation, der optokinetische Nystagmus und Augenfolgebewegungen oder Symptome, die auf eine schwere Hirnstammschädigung hinweisen wie eine Dezerebrationshaltung, wurden als Ausschlusskriterien eines APS vorgeschlagen. Zusammenfassung: Die Erweiterung der MSTF-Diagnosekriterien um obligatorische und unterstützende Schlüsselsymptome sowie klar definierte Ausschlusskriterien erleichtert die klinische Differentialdiagnose des APS und führt zu einer größeren Diagnosesicherheit des Syndroms. / Objective: Although the Multi Society Task Force (MSTF) on persistent vegetative state (PVS) published diagnostic criteria ten years ago, differentiation of PVS from similar syndromes remains a diagnostic challenge. The aim of our study was the prospective identification of clinically assessable symptoms supplementary to the MSTF criteria which supports or rejects the diagnosis of a PVS and to reevaluate the parameters after 30 month. Design: Prospective diagnostic study Setting: The 90-bed department of Neurology of the University hospital of Berlin. Patients and participants: Out of 24 screened patients with the differential diagnosis PVS, 16 patients were finally included to the study and prospectively assessed by a clinical examination, comprising spontaneous and reflexive motor activities, primitive reflexes, habituation and eye movements. Measurements and results: Mandatory symptoms of the MSTF were found in all 16 patients. In addition, clinical features like spontaneous automatisms (n=12), periodic alternating gaze deviation (n=12), startle reaction to external stimuli (n=10), and spastic muscular tone (n=9) were found frequently and considered supportive for the diagnosis. In contrast to previous observations, periodic alternating eye movements and increased muscular tone were found more frequently in our patients. Symptoms linked to a preserved consciousness like reflexive visually guided saccades, habituation, an optokinetic nystagmus and eye tracking or symptoms indicating a severe functional impairment of the brainstem like a decerebrated posture were proposed as excluding PVS. Conclusion: The application of mandatory and supportive symptoms lead to a further improvement of diagnostic certainty in PVS, particular in patient presenting exceptional clinical phenomena. Clearly defined exclusive criteria prevent from misdiagnosis.

The aim of this thesis is to inform in detail about the latest clinical and nursing practice trends concerning the needs of patients in vegetative state and their carers. It also deals with relations in the system of long-term nursing care, providing medical and social services and rehabilitation. It also tries to point out the most pressing problems of the current situation of patients in vegetative state and their families, especially in terms of patient discharge to home care and availability of services specified for this target group. The latest findings and proven methods will be summarized in a simple and understandable form, which will serve as a guide both for health professionals and caregivers.For this thesis the Review and synthesis method will be used. The overview of current knowledge and studies in the field of care for patients in vegetative state will be synthesized and focused on home care with recommendations for practice and indications of weak spots.Long-term follow-up nursing and rehabilitative care is necessary for these patients. A special chapter is focused on the specific needs of patients in vegetative state and appropriate nursing care, rehabilitation and release issues. The fundamental part is the consistency of formal and informal care, caregiver preparation for their future role and related socio-economic issues. In conclusion the legal and ethical aspects of the whole field are mentioned regarding medical and nursing care of patients in vegetative state.In line with the objective of this thesis a manual will be created for potential informal carers on how to care for their loved ones, where to go in the case of emergency and what steps to take during the intermediate stage of institutional and home care. The results can be used for further exploration and as an additional source of information for health professionals.

Le coma, l’état végétatif et l’état de conscience minimale sont classés comme « troubles de la conscience ». La caractéristique commune à ces diagnostics est un état de conscience altéré. La technologie permet désormais de maintenir en vie les individus affligés de ces diagnostics. La nature même de leur condition et les soins disponibles pour ces patients conduisent à des dilemmes médicaux et éthiques importants. Ce mémoire propose une brève introduction des troubles de la conscience suivie d’une recension des écrits sur les enjeux éthiques et sociaux en lien avec ces diagnostics. Force est de constater que certains enjeux perdurent depuis des années comme le retrait de traitement. D’autres sont apparus plus récemment, comme l’enjeu lié à l’usage de la neuroimagerie. Un deuxième volet présente les résultats d’une étude qualitative examinant les perspectives et l’expérience des professionnels de la santé face aux enjeux éthiques lors de la prise en charge des patients atteints de troubles de la conscience. Cette étude a été réalisée par le biais d’un court questionnaire et d’entrevues semi-dirigées qui furent enregistrées puis analysées à l’aide du logiciel Nvivo. Les résultats démontrent entre autres que les répondants éprouvent un niveau de certitude élevé face au diagnostic bien qu’il soit souvent signalé comme un défi important dans la littérature. Le pronostic représente un enjeu crucial, y compris sa divulgation aux proches. Enfin, la relation avec la famille est un élément clé dans la prise en charge des patients et celle-ci est teintée par de multiples facteurs. / Coma, the vegetative state and the minimally conscious state are classified as “disorders of consciousness”. The common characteristic of these diagnoses is an altered state of consciousness. Technological advances now allow us to keep people afflicted with these diagnoses alive. The very nature of their condition and the type of care available to them has lead to important medical and ethical dilemmas. First, this thesis proposes a literature review of the ethical and social issues related to disorders of consciousness. Certain issues have persisted for years and others have emerged more recently as that relating to the use of neuroimaging. The second part proposes a qualitative study examining the perspectives and experiences of healthcare professionals dealing with ethical issues in the management of these patients; these aspects are so far poorly documented. We conducted this study using a short questionnaire and semi-directed interviews. The interviews were taped and analyzed using qualitative analysis software Nvivo. Our study showed that our participants experienced a high degree of certainty about the diagnosis, although the latter is often reported as a major challenge in the literature. The prognosis is a critical challenge, including its disclosure to relatives. Finally, the relationship with the family is a key element in the care of patients and it is influenced by multiple factors.

La presente tesi utilizza la metodologia neuroscientifica per studiare la comunicazione dal punto di vista della embodied cognition, la quale vede la comunicazione come la condivisione dell’informazione tra organismi biologici. Lo scopo della tesi è quello di aggiungere conoscenza in aree della comunicazione in cui l’applicazione delle neuroscienze è carente, usando una metodologia integrata che prevede la coregistrazione EEG-Biofeedback. All’interno della tematica della comunicazione mediata, il primo studio compara le pubblicità commerciale e prosociale, poiché l’applicazione delle neuroscienze a quest’ultima risulta carente. Lo scopo è quello di investigare l’esperienza relativa a questi due tipi di comunicazione, all’interno di differenti categorie semantiche di prodotto, confrontando misure implicite ed esplicite. Un secondo studio vuole illustrare il coinvolgimento di cues comunicative sensoriali durante l’esperienza del consumatore, esplorando diverse condizioni di stimolazione sensoriale entro un negozio per studiarne, a livello cerebrale, la loro interazione. Se la comunicazione possiede diversi livelli di consapevolezza, è possibile studiarla anche all’interno di condizioni patologiche. Un terzo studio, quindi, vuole trovare risposte ad alcuni interrogativi circa le componenti inconsce della comunicazione. In particolare, lo studio vuole valutare i processi sensoriali e cognitivi residui relativi al tatto in pazienti in stato vegetativo. / The present thesis fits the neuroscientific method to the embodied communication perspective, which defines communication as an information sharing between biological bodies. The aim of this thesis is to increase knowledge into different research areas related to communication, in which the application of neurosciences is already lacking, using a multimethod approach that employs EEG-Biofeedback co-registration. Within the topic of mediated communication, the first study compares commercial and social-issue advertising, given the lack of studies that investigate the latter with a neuroscientific approach. The aim is to investigate the experience of watching these two types of advertising, through different product categories, comparing overt and covert measures. A second study has the aim to illustrate the involvement of sensory communication cues during consumer experience, exploring different conditions of sensory stimulation inside a store, in order to understand the interaction between senses in the consumer’s brain. If communication can be seen as a continuum with multiple degrees of awareness, it can be also studied in clinical and pathological conditions. A third study, thus, tries to find answers to open questions about unconscious components of communication. In particular, the study assesses residual sensory and cognitive processes related to touch in vegetative state patients.

Le coma, l’état végétatif et l’état de conscience minimale sont classés comme « troubles de la conscience ». La caractéristique commune à ces diagnostics est un état de conscience altéré. La technologie permet désormais de maintenir en vie les individus affligés de ces diagnostics. La nature même de leur condition et les soins disponibles pour ces patients conduisent à des dilemmes médicaux et éthiques importants. Ce mémoire propose une brève introduction des troubles de la conscience suivie d’une recension des écrits sur les enjeux éthiques et sociaux en lien avec ces diagnostics. Force est de constater que certains enjeux perdurent depuis des années comme le retrait de traitement. D’autres sont apparus plus récemment, comme l’enjeu lié à l’usage de la neuroimagerie. Un deuxième volet présente les résultats d’une étude qualitative examinant les perspectives et l’expérience des professionnels de la santé face aux enjeux éthiques lors de la prise en charge des patients atteints de troubles de la conscience. Cette étude a été réalisée par le biais d’un court questionnaire et d’entrevues semi-dirigées qui furent enregistrées puis analysées à l’aide du logiciel Nvivo. Les résultats démontrent entre autres que les répondants éprouvent un niveau de certitude élevé face au diagnostic bien qu’il soit souvent signalé comme un défi important dans la littérature. Le pronostic représente un enjeu crucial, y compris sa divulgation aux proches. Enfin, la relation avec la famille est un élément clé dans la prise en charge des patients et celle-ci est teintée par de multiples facteurs. / Coma, the vegetative state and the minimally conscious state are classified as “disorders of consciousness”. The common characteristic of these diagnoses is an altered state of consciousness. Technological advances now allow us to keep people afflicted with these diagnoses alive. The very nature of their condition and the type of care available to them has lead to important medical and ethical dilemmas. First, this thesis proposes a literature review of the ethical and social issues related to disorders of consciousness. Certain issues have persisted for years and others have emerged more recently as that relating to the use of neuroimaging. The second part proposes a qualitative study examining the perspectives and experiences of healthcare professionals dealing with ethical issues in the management of these patients; these aspects are so far poorly documented. We conducted this study using a short questionnaire and semi-directed interviews. The interviews were taped and analyzed using qualitative analysis software Nvivo. Our study showed that our participants experienced a high degree of certainty about the diagnosis, although the latter is often reported as a major challenge in the literature. The prognosis is a critical challenge, including its disclosure to relatives. Finally, the relationship with the family is a key element in the care of patients and it is influenced by multiple factors.

A assistência aos pacientes com doenças neurológicas de longa duração não é reconhecida na produção científica brasileira; entende-se por doença neurológica de longa duração: doenças neurológicas de curso longo, fase final de difícil identificação, com sintomas variados e condição de dependência moderada ou grave e comprometimento cognitivo de difícil avaliação. Neste estudo, foram consideradas as seguintes condições: estado vegetativo persistente, estado mínimo de consciência e síndrome do encarceramento (ou síndrome de locked-in). Em busca bibliográfica, verificou-se que não há artigo em língua portuguesa sobre o tema. No cotidiano, a assistência é focada em higiene e observação clínica. Entretanto, na perspectiva do Cuidado, algo mais é necessário ao se pensar este tipo de prática, para a promoção da dignidade humana. Os objetivos deste estudo são: relatar uma prática junto a pessoas com doenças neurológicas de longa duração focada no seu resgate biográfico, e fundamentar a mesma de maneira interdisciplinar, a partir do Cuidado como categoria reconstrutiva. É uma pesquisa qualitativa, na qual foram utilizados primariamente registros de um diário de campo da primeira autora, sobre intervenções em Terapia Ocupacional com esta população; a partir destes, foram produzidas narrativas e reflexões sobre a metodologia de intervenção. A partir do resgate biográfico, busca-se resgatar a condição de sujeito do paciente neurológico muito grave. Na segunda etapa, tem-se a fundamentação teórica numa perspectiva interdisciplinar; o conceito de Cuidado é a referência principal, compreendido como o sentido existencial da experiência de adoecimento. Também foi utilizado o referencial da psicanálise de orientação freudiana e lacaniana para aprofundamento teórico dos achados empíricos descritos através de narrativas. A reconstrução da biografia do paciente ocorre por diversas perspectivas, mas especialmente pela estimulação sensorial - não com foco de recuperação neurológicas, mas a partir do repertório do paciente e em busca da validação de sua condição de sujeito. Junto com uma detalhada avaliação e acompanhamento, o terapeuta faz um monitoramento contínuo, propondo atividades e dando especial atenção ás reações observadas, para que possa nomeá-las ou traduzi-las, bem como discriminar os estímulos agradáveis e desagradáveis; isto também possibilita ampliação das possibilidades de encontro deste sujeito com o mundo. Os conceitos psicanalíticos: estágio do espelho, real, lalíngua e constituição do sujeito apresentam-se como fundamentais para a compreensão das experiências empíricas vividas e, posteriormente, elaboração de uma fundamentação teórica. Memória, história, identidade, dignidade e subjetividade qualificam a prática junto a pessoas com doenças neurológicas de longa duração. A despeito das reações neurológicas apresentadas, tal prática possibilita a reconstrução de um cotidiano significativo e as teorias psicanalíticas de orientação freudiana e lacaniana constituem importante marco para fundamentação da reconstrução da assistência / The care of people with Long Term Neurological Conditions (LTNC) isn´t recognized in the Brazilian Palliative Care scientific production; in daily basis, the assistance is focussed on hygiene´s care and clinical observation. However, from the perspective of palliative care, something more is needed, to promote the dignity of the human person. To describe an occupational therapy intervention for patients with LTNC based on biographical rescue. Records and field diaries of an Occupational Therapy intervention promoted by the first author were used to produce narratives and reflections about this intervention´s methodology. The concept of Comprehensive Care is the main reference, designed as care interested in the existential sense of the illness process. It was also used the framework of Freud´s and Lacan´s psychoanalysis for theoretical studies of the empirical findings reported through narratives. The beginning of the reconstruction of the patient´s biography occurs by several perspectives, especially through sensory stimuli related to prior patient´s occupational repertoire. Along with the detailed evaluation, the therapist does a careful and continuous monitoring, proposing activities, giving special attention to their reactions, being able to discriminate what pleases or not, and expanding the possibilities of encounter of people with LTNC and the environment which surround them. The psychoanalytic concepts: mirror stage, real, lalangue and subject´s constitution had major importance to understand the empirical experiences and to develop a theoretical basis. Memory, history, identity, dignity, and subjectivity qualify the practice of occupational therapist with people with LTNC. Regardless of neurological reactions presented by the patients this practice helps reconstructing the meanings of the daily life of person with so severe disability. Sensory stimuli are shown as potential tools for a reconfiguration of the assistance with someone seriously affected by a neurological disease. Psychoanalytic theories of Freudian and Lacanian orientation are also an important framework for the reconstruction assistance

People can differ in their attitudes toward apalic syndrome patients. Health care staff, however, would always be professional. They deal with a human being, a person who can sense. This fact should form a framework for both health care professionals and patients´ families. Especially nurses should be very sensitive, calm and good-tempered so that they could take adequate care of apalic patients. The empiric part of the thesis was elaborated through qualitative and quantitative research survey. The qualitative method, an interview, was used in the first phase of the survey. The data were collected through semi-structured interviews with the family members of apalic patients and the nurses of health care facilities. Although the interviews for the family members and the nurses differed in some parts, they contained common identification questions and specific information. The interviews were anonymous and consisted of 16 questions for the family members and 10 questions for the nurses.