ÉVALUATION DE LA PERCEPTION CONSCIENTE CHEZ DES PATIENTS NON COMMUNICATIFS :Approche comportementale et par neuroimagerie

RÉSUMÉSuite à un accident cérébral grave, qu’il soit traumatique ou hypoxique-ischémique, les patients peuvent évoluer d’un coma (patient non-éveillable et inconscient) vers un état végétatif (patient éveillé mais inconscient), un état de conscience minimale (patient éveillé et conscient, mais non-communiquant), ou un locked-in syndrome (patient éveillé, conscient, mais ne pouvant exprimer cette conscience que par le biais de mouvements oculaires) (Vanhaudenhuyse et al., 2009a). Notre but est de mettre au point des techniques permettant de détecter des signes de conscience chez ces patients incapables de communiquer, que ce soit par des évaluations comportementales, l’électroencéphalographie ou la neuroimagerie. Etudes comportementales : Actuellement, malgré les nouveaux critères de conscience proposés par Giacino et al. en 2002, nous avons pu démontrer que jusqu’à 40% des patients étaient diagnostiqués comme étant en état végétatif, alors qu’ils étaient en réalité en état de conscience minimale (Schnakers, Vanhaudenhuyse et al., 2009b). Nos travaux ont mis en évidence que l’absence d’outil d’évaluation de la conscience standardisé pouvait expliquer la difficulté à détecter des signes de conscience. Nous avons démontré que la poursuite visuelle, qui est un des premiers signes de conscience réapparaissant chez les patients récupérant de l’état végétatif, était significativement mieux détectée lorsqu’elle était évaluée à l’aide d’un miroir (Vanhaudenhuyse et al., 2008c). L’absence de consensus sur la signification de certains comportements, en termes de conscience, peut également être à la source de problèmes diagnostiques. Nous avons, par exemple, démontré que le clignement à la menace visuelle, comportement ambigu de conscience, était compatible avec le diagnostic d’état végétatif et qu’il n’avait pas de valeur pronostique de récupération de conscience (Vanhaudenhuyse et al., 2008a).Marqueurs électrophysiologiques : Distinguer un comportement volontaire d’un comportement réflexe reste difficile, ce qui nous pousse à étudier d’autres techniques permettant d’obtenir des marqueurs objectifs de conscience. Nous avons souligné l’intérêt des potentiels évoqués de courte latence comme marqueurs d’un mauvais pronostic, ainsi que des potentiels évoqués cognitifs pour évaluer la récupération d’une conscience et les fonctions cognitives résiduelles des patients en coma et post-coma (Vanhaudenhuyse et al., 2008b). Neuroimagerie fonctionnelle et structurelle : Par l’Imagerie par Résonance Magnétique fonctionnelle (IRMf), nous avons pu mettre au point différents paradigmes d’aide au diagnostic d’état de conscience altérée de ces patients. L’étude du réseau du mode par défaut, c’est-à-dire de l’ensemble des régions cérébrales activées lorsque nous sommes au repos et éveillés (précunéus, cortex mésio-frontal, jonctions temporo-pariétales), nous a permis de développer un outil facile à appliquer en routine clinique. Nous avons mis en évidence une corrélation négative non-linéaire entre la connectivité au sein du réseau du mode par défaut et le degré de conscience des patients (coma, état végétatif, état de conscience minimale et locked-in syndrome – Vanhaudenhuyse et al., 2010b). Par ailleurs, en collaboration avec l’équipe du MRC Cognition and Brain Sciences Unit de Cambridge, nous avons appliqué des paradigmes actifs en IRMf, durant lesquels 54 patients devaient réaliser activement des tâches cognitives (s’imaginer jouer au tennis, s’imaginer visiter sa maison). Sur 23 patients diagnostiqués comme étant en état végétatif, 4 d’entre eux (17%) étaient capables de moduler volontairement leur activité neuronale (Monti & Vanhaudenhuyse et al., 2010). De plus, ce paradigme a permis à un de ces patients, chez qui aucune communication n’était possible, de répondre à l’aide d’un code oui (imaginez jouer au tennis) / non (imaginez visiter votre maison) à des questions autobiographiques. Cependant, ce type de méthode est difficilement utilisable au quotidien. Dès lors, nous développons des interfaces cerveau-ordinateur transportables grâce au projet européen WF7 DECODER. Une de ces techniques de communication a pu être proposée par la modulation du pH salivaire chez un sujet sain (Vanhaudenhuyse et al., 2007a). Enfin, dans le cadre d’études multicentriques dirigées par le Pr. Louis Puybasset (Hôpital de la Pitié-Salpétrière, Paris), nous avons mis en évidence l’intérêt diagnostique et pronostique de séquences telles que l’imagerie par tenseur de diffusion et la spectroscopie (Tshibanda & Vanhaudenhuyse et al., 2009 ; 2010). Au terme de ce travail, nous proposons des perspectives de nouvelles études à entreprendre afin d’améliorer les évaluations comportementales, mais aussi les paradigmes d’acquisition en IRM et en EEG que nous avons à notre disposition. Notre projet est de développer des recherches translationnelles validées pour une application clinique individuelle. Nous espérons que cette approche multimodale permettra d’améliorer la prise en charge des patients sévèrement cérébrolésés qui sont toujours un véritable défi pour le corps médical, mais aussi d’accroître nos connaissances sur la conscience humaine.SUMMARYSurvivors of severe traumatic or hypoxic-ischemic brain damage classically go through different clinical entities such as coma (unarousable unconsciousness), vegetative state (characterized by wakefulness without awareness), minimally conscious state (minimal but definite evidence of awareness without communication) or locked-in syndrome (fully aware but unable to move or speak) (Vanhaudenhuyse et al., 2009a). Our goal is to improve and develop methods to detect consciousness in these non-communicative patients by using bedside behavioral examinations and para-clinical electroencephalography or neuroimaging techniques. Behavioral examination: Bedside assessment is one of the main methods used to detect awareness in severely brain injured patients recovering from coma. However, our prospective multicentric study showed that up to 40% of patients may be diagnosed as vegetative while they are in reality in a minimally conscious state (Schnakers, Vanhaudenhuyse et al., 2009b). The failure to use standardized behavioral assessment tools and the absence of consensus about some clinical behaviors could explain the difficulty to identify signs of consciousness. For example, we showed that clinicians should use a mirror when evaluating visual pursuit, a behavior that is one of the first differentiating minimally conscious from vegetative patients (Vanhaudenhuyse et al., 2008c). Similarly, the blinking to visual threat remains an ambiguous clinical sign of consciousness. We showed that this behavior may be a common clinical feature of the vegetative state and that its presence does not necessarily herald consciousness nor recovery of consciousness in patients with severe brain injury (Vanhaudenhuyse et al., 2008a).Electrophysiological markers: EEG methods offer objective assessment procedures and the possibility to determine whether an unresponsive patient is aware without explicit verbal or motor response. While early evoked-potentials are good prognosticators of bad outcome, cognitive evoked-potentials appear to be good predictors of favourable outcome and may be helpful to estimate the residual cognitive functions of comatose and post-comatose patients (Vanhaudenhuyse et al., 2008b). Functional and structural neuroimaging: By using functional Magnetic Resonance Imaging (fMRI), we first studied the brain spontaneous activity and next used it to identify signs of consciousness and communication in these patients. Studies of default mode network in fMRI, i.e. brain regions encompassing precuneus, medial prefrontal cortex and temporo-parietal junctions which are more active at rest, are easy to perform and could have a potentially broader and faster translation into clinical practice. We showed a negative non-linear correlation between default mode network connectivity and the level of consciousness of brain-damaged patients (ranging from coma, vegetative state, minimally conscious state to locked-in syndrome – Vanhaudenhuyse et al., 2010b). In collaboration with the MRC Cognition and Brain Sciences Unit in Cambridge, we applied active paradigms in fMRI (in which patients were asked to imagine playing tennis and visiting their house) in 54 patients. We showed that out of 23 vegetative patients, 4 (17%) were able to voluntary modulate their neuronal brain activity. Moreover, one of these patients, who was not able to behaviorally communicate, showed the ability to apply the imagery technique in order to answer accurately simple yes (imagine playing tennis) / no (imagine visiting your house) questions (Monti & Vanhaudenhuyse et al., 2010). However, this technique will not be useful in the daily life of these patients. Thus, we developed appropriate brain computer interfaces with our European partners of the WF7 DECODER project. For example, we showed that one of these methods could be the mental manipulation of salivary pH as a form of non-motor mediated communication (Vanhaudenhuyse et al., 2007a). Finally, international multi-centric studies leaded by Pr. Louis Puybasset (Pitié-Salpétrière Hospital, Paris) are validating the diagnostic and prognostic interests of MRI sequences such as diffusion tensor and spectroscopy imaging to evaluate the prognosis of recovery of severely brain injured patients (Tshibanda & Vanhaudenhuyse et al., 2009 ; 2010). Future ongoing studies are continuing to improve our actual behavioral assessments, MRI and EEG measurements in disorders of consciousness. Our project is to validate translational research models that can be applied at the individual patient level. We hope that our multimodal and multidisciplinary approach will improve our medical care for brain-damaged patients suffering from disorders of consciousness and additionally shed some light to our understanding of the neural correlates of human consciousness

Neurophysiologie de l’hypnose

We here review behavioral, neuroimaging and electrophysiological studies of hypnosis as a state, as well as hypnosis as a tool to modulate brain responses to painful stimulations. Studies have shown that hypnotic processes modify internal (self awareness) as well as external (environmental awareness) brain networks. Brain mechanisms underlying the modulation of pain perception under hypnotic conditions involve cortical as well as subcortical areas including anterior cingulate and prefrontal cortices, basal ganglia and thalami. Combined with local anesthesia and conscious sedation in patients undergoing surgery, hypnosis is associated with improved peri- and postoperative comfort of patients and surgeons. Finally, hypnosis can be considered as a useful analogue for simulating conversion and dissociation symptoms in healthy subjects, permitting better characterization of these challenging disorders by producing clinically similar experiences

Connectivity graph analysis of the auditory resting state network in tinnitus.

Thirteen chronic tinnitus patients and fifteen age-matched healthy controls were studied on a 3T magnetic resonance imaging (MRI) scanner during resting condition (i.e. eyes closed, no task performance). The auditory resting-state component was selected using an automatic component selection approach. Functional connectivity (correlations/anti-correlations) in the extracted network was portrayed by integrating the independent component analysis (ICA) approach with a graph theory method. Tinnitus and control groups showed different graph connectivity patterns. In the control group, the connectivity graph was divided into two distinct anti-correlated networks. The first one encompassed the auditory cortices and the insula. The second one encompassed frontoparietal and anterior cingulate cortices, brainstem, amygdala, basal ganglia/nucleus accumbens and parahippocampal regions. In the tinnitus group, only one of the two previously described networks was observed, encompassing the auditory cortices and the insula. Direct group comparison showed, in the tinnitus group, an increased functional connectivity between auditory cortices and the left parahippocampal region surviving multiple comparisons. We investigated a possible correlation between four tinnitus relevant measures (tinnitus handicap inventory (THI) and tinnitus questionnaire (TQ) scores, tinnitus duration and tinnitus intensity during the scanning session) and the connectivity pattern in the tinnitus population. We observed a significant positive correlation between the beta values of the posterior cingulate/precuneus region and the THI score. Our results show a modified functional connectivity pattern in tinnitus sufferers and highlight the role of the parahippocampal region in tinnitus physiopathology. They also point out the importance of the activity and connectivity pattern of the posterior cingulate cortex/precuneus region to the development of the tinnitus associated distress. This article is part of a Special Issue entitled: Tinnitus Neuroscience

Self-Compassion-Based Interventions in Oncology: A Review of Current Practices

peer reviewe

La transe cognitive auto-induite : caractéristiques et applications thérapeutiques potentielles.

peer reviewe

Neural Plasticity Lessons from Disorders of Consciousness

Communication and intentional behavior are supported by the brain's integrity at a structural and a functional level. When widespread loss of cerebral connectivity is brought about as a result of a severe brain injury, in many cases patients are not capable of conscious interactive behavior and are said to suffer from disorders of consciousness (e.g., coma, vegetative state/unresponsive wakefulness syndrome, minimally conscious states). This lesion paradigm has offered not only clinical insights, as how to improve diagnosis, prognosis, and treatment, but also put forward scientific opportunities to study the brain's plastic abilities. We here review interventional and observational studies performed in severely brain-injured patients with regards to recovery of consciousness. The study of the recovered conscious brain (spontaneous and/or after surgical or pharmacologic interventions), suggests a link between some specific brain areas and the capacity of the brain to sustain conscious experience, challenging at the same time the notion of fixed temporal boundaries in rehabilitative processes. Altered functional connectivity, cerebral structural reorganization as well as behavioral amelioration after invasive treatments will be discussed as the main indices for plasticity in these challenging patients. The study of patients with chronic disorders of consciousness may, thus, provide further insights not only at a clinical level (i.e., medical management and rehabilitation) but also from a scientific-theoretical perspective (i.e., the brain's plastic abilities and the pursuit of the neural correlate of consciousness)

Neuroimaging after coma.

Following coma, some patients will recover wakefulness without signs of consciousness (only showing reflex movements, i.e., the vegetative state) or may show non-reflex movements but remain without functional communication (i.e., the minimally conscious state). Currently, there remains a high rate of misdiagnosis of the vegetative state (Schnakers et. al. BMC Neurol, 9:35, 8) and the clinical and electrophysiological markers of outcome from the vegetative and minimally conscious states remain unsatisfactory. This should incite clinicians to use multimodal assessment to detect objective signs of consciousness and validate para-clinical prognostic markers in these challenging patients. This review will focus on advanced magnetic resonance imaging (MRI) techniques such as magnetic resonance spectroscopy, diffusion tensor imaging, and functional MRI (fMRI studies in both "activation" and "resting state" conditions) that were recently introduced in the assessment of patients with chronic disorders of consciousness

Structural brain injury in patients with disorders of consciousness: A voxel-based morphometry study.

MAIN OBJECTIVE: Disorders of consciousness (DOC; encompassing coma, vegetative state/unresponsive wakefulness syndrome (VS/UWS) and minimally conscious state minus/plus (MCS-/+)) are associated with structural brain injury. The extent of this damage remains poorly understood and merits a detailed examination using novel analysis techniques. Research design/methods and procedures: This study used voxel-based morphometry (VBM) on structural magnetic resonance imaging scans of 61 patients with DOC to examine grey and white matter injury associated with DOC, time spent in DOC, aetiology and diagnosis. MAIN OUTCOMES AND RESULTS: DOC and time spent in DOC were found to be associated with widespread structural brain injury, although the latter did not correlate strongly with injury in the right cerebral hemisphere. Traumatic, as compared to non-traumatic aetiology, was related to more injury in the brainstem, midbrain, thalamus, hypothalamus, basal forebrain, cerebellum, and posterior corpus callosum. Potential structural differences were found between VS/UWS and MCS and between MCS- and MCS+, but need further examination. CONCLUSIONS: The findings indicate that both traumatic and non-traumatic DOC are associated with widespread structural brain injury, although differences exist that could lead to aetiology-specific treatment strategies. Furthermore, the high degree of atrophy occurring after initial brain injury prompts the development and use of neuroprotective techniques to potentially increase patients\u27 chances of recovery

Behavioural and brain responses in cognitive trance: A TMS-EEG case study.

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Psychological interventions influence patients' attitudes and beliefs about their chronic pain.

Background: Patients' changing attitudes and beliefs about pain are considered as improvements in the treatment of chronic pain. Multidisciplinary approaches to pain allow modifications of coping strategies of patients, from passive to active. Methods: We investigate how two therapeutic treatments impact patients' attitudes and beliefs regarding pain, as measured with the Survey of Pain Attitudes (SOPA). We allocated 415 patients with chronic pain either to psychoeducation combined with physiotherapy, self-hypnosis combined with self-care learning, or to control groups. Pain intensity, global impression of change, and beliefs and attitudes regarding pain were assessed before and after treatment. Results: Our main results showed a significant effect of psychoeducation/physiotherapy on control, harm, and medical cure SOPA subscales; and a significant effect of self-hypnosis/self-care on control, disability and medical cure subscales. Correlation results showed that pain perception was negatively associated with control, while positively associated with disability, and a belief that hurt signifies harm. Patients' impression of improvement was associated with greater control, lower disability, and lower belief that hurt signifies harm. Conclusions: The present study showed that self-hypnosis/self-care and psychoeducation/physiotherapy were associated with patients' evolution of coping strategies from passive to active, allowing them to reduce pain perception and improve their global impression of treatment effectiveness. Keywords: Chronic pain, Hypnosis, Psychoeducation, Coping, Pain belief