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See detailFunctional neuroanatomy underlying the clinical subcategorization of minimally conscious state patients.
Bruno, Marie-Aurélie ULg; Majerus, Steve ULg; Boly, Mélanie ULg et al

in Journal of Neurology (2012), 259(6), 1087-98

Patients in a minimally conscious state (MCS) show restricted signs of awareness but are unable to communicate. We assessed cerebral glucose metabolism in MCS patients and tested the hypothesis that this ... [more ▼]

Patients in a minimally conscious state (MCS) show restricted signs of awareness but are unable to communicate. We assessed cerebral glucose metabolism in MCS patients and tested the hypothesis that this entity can be subcategorized into MCS- (i.e., patients only showing nonreflex behavior such as visual pursuit, localization of noxious stimulation and/or contingent behavior) and MCS+ (i.e., patients showing command following).Patterns of cerebral glucose metabolism were studied using [(18)F]-fluorodeoxyglucose-PET in 39 healthy volunteers (aged 46 +/- 18 years) and 27 MCS patients of whom 13 were MCS- (aged 49 +/- 19 years; 4 traumatic; 21 +/- 23 months post injury) and 14 MCS+ (aged 43 +/- 19 years; 5 traumatic; 19 +/- 26 months post injury). Results were thresholded for significance at false discovery rate corrected p < 0.05.We observed a metabolic impairment in a bilateral subcortical (thalamus and caudate) and cortical (fronto-temporo-parietal) network in nontraumatic and traumatic MCS patients. Compared to MCS-, patients in MCS+ showed higher cerebral metabolism in left-sided cortical areas encompassing the language network, premotor, presupplementary motor, and sensorimotor cortices. A functional connectivity study showed that Broca's region was disconnected from the rest of the language network, mesiofrontal and cerebellar areas in MCS- as compared to MCS+ patients.The proposed subcategorization of MCS based on the presence or absence of command following showed a different functional neuroanatomy. MCS- is characterized by preserved right hemispheric cortical metabolism interpreted as evidence of residual sensory consciousness. MCS+ patients showed preserved metabolism and functional connectivity in language networks arguably reflecting some additional higher order or extended consciousness albeit devoid of clinical verbal or nonverbal expression. [less ▲]

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See detailRecovery of cortical effective connectivity and recovery of consciousness in vegetative patients.
Rosanova, Mario; Gosseries, Olivia ULg; Casarotto, Silvia et al

in Brain : A Journal of Neurology (2012), 135(Pt 4), 1308-20

Patients surviving severe brain injury may regain consciousness without recovering their ability to understand, move and communicate. Recently, electrophysiological and neuroimaging approaches, employing ... [more ▼]

Patients surviving severe brain injury may regain consciousness without recovering their ability to understand, move and communicate. Recently, electrophysiological and neuroimaging approaches, employing simple sensory stimulations or verbal commands, have proven useful in detecting higher order processing and, in some cases, in establishing some degree of communication in brain-injured subjects with severe impairment of motor function. To complement these approaches, it would be useful to develop methods to detect recovery of consciousness in ways that do not depend on the integrity of sensory pathways or on the subject's ability to comprehend or carry out instructions. As suggested by theoretical and experimental work, a key requirement for consciousness is that multiple, specialized cortical areas can engage in rapid causal interactions (effective connectivity). Here, we employ transcranial magnetic stimulation together with high-density electroencephalography to evaluate effective connectivity at the bedside of severely brain injured, non-communicating subjects. In patients in a vegetative state, who were open-eyed, behaviourally awake but unresponsive, transcranial magnetic stimulation triggered a simple, local response indicating a breakdown of effective connectivity, similar to the one previously observed in unconscious sleeping or anaesthetized subjects. In contrast, in minimally conscious patients, who showed fluctuating signs of non-reflexive behaviour, transcranial magnetic stimulation invariably triggered complex activations that sequentially involved distant cortical areas ipsi- and contralateral to the site of stimulation, similar to activations we recorded in locked-in, conscious patients. Longitudinal measurements performed in patients who gradually recovered consciousness revealed that this clear-cut change in effective connectivity could occur at an early stage, before reliable communication was established with the subject and before the spontaneous electroencephalogram showed significant modifications. Measurements of effective connectivity by means of transcranial magnetic stimulation combined with electroencephalography can be performed at the bedside while by-passing subcortical afferent and efferent pathways, and without requiring active participation of subjects or language comprehension; hence, they offer an effective way to detect and track recovery of consciousness in brain-injured patients who are unable to exchange information with the external environment. [less ▲]

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See detailBrain connectivity in disorders of consciousness.
Boly, Mélanie ULg; Massimini, Marcello; Garrido, Marta Isabel et al

in Brain connectivity (2012), 2(1), 1-10

The last 10 years witnessed a considerable increase in our knowledge of brain function in survivors to severe brain injuries with disorders of consciousness (DOC). At the same time, a growing interest ... [more ▼]

The last 10 years witnessed a considerable increase in our knowledge of brain function in survivors to severe brain injuries with disorders of consciousness (DOC). At the same time, a growing interest developed for the use of functional neuroimaging as a new diagnostic tool in these patients. In this context, particular attention has been devoted to connectivity studies-as these, more than measures of brain metabolism, may be more appropriate to capture the dynamics of large populations of neurons. Here, we will review the pros and cons of various connectivity methods as potential diagnostic tools in brain-damaged patients with DOC. We will also discuss the relevance of the study of the level versus the contents of consciousness in this context. [less ▲]

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See detailHierarchical clustering of brain activity during human nonrapid eye movement sleep.
Boly, Mélanie ULg; Perlbarg, V; Marrelec, G et al

in Proceedings of the National Academy of Sciences of the United States of America (2012)

Consciousness is reduced during nonrapid eye movement (NREM) sleep due to changes in brain function that are still poorly understood. Here, we tested the hypothesis that impaired consciousness during NREM ... [more ▼]

Consciousness is reduced during nonrapid eye movement (NREM) sleep due to changes in brain function that are still poorly understood. Here, we tested the hypothesis that impaired consciousness during NREM sleep is associated with an increased modularity of brain activity. Cerebral connectivity was quantified in resting-state functional magnetic resonance imaging times series acquired in 13 healthy volunteers during wakefulness and NREM sleep. The analysis revealed a modification of the hierarchical organization of large-scale networks into smaller independent modules during NREM sleep, independently from EEG markers of the slow oscillation. Such modifications in brain connectivity, possibly driven by sleep ultraslow oscillations, could hinder the brain's ability to integrate information and account for decreased consciousness during NREM sleep. [less ▲]

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See detailEnd-of-life attitudes are mediated by opinions of pain perception in patients with disorders of consciousness
Demertzi, Athina ULg; Bruno, Marie-Aurelie; LEDOUX, Didier ULg et al

Conference (2011, November 16)

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See detailLe Sommeil dans l'Etat Végétatif et de Conscience Minimale
Cologan, Victor ULg; Drouot, Xavier; Parapatics, Silvia et al

Poster (2011, November)

Présentation des résultats de l'étude du sommeil chez les patients cérébrolésés en état de conscience altéré.

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See detailWachkoma: medizinische Grundlagen und neurowissenschaftliche Revolution
Demertzi, Athina ULg; Schabus; Weilhart, K. et al

in Jox, R.; Borasio, G. D.; Kühlmeyer, K. (Eds.) Leben im Koma Interdisziplinäre Perspektiven auf das Problem des Wachkomas (2011)

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See detailDesign of a novel covert SSVEP-based BCI
Lesenfants, Damien ULg; Partoune, Nicolas; Soddu, Andrea ULg et al

in Proceedings of the 5th International Brain-Computer Interface Conference 2011 (2011, September 22)

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See detailDésordres de la conscience : aspects éthiques.
Demertzi, Athina ULg; Gosseries, Olivia ULg; Bruno, Marie-Aurélie ULg et al

in Schnakers, Caroline; LAUREYS, Steven (Eds.) Comas et états de conscience altérée (2011)

L’apparition de la ventilation mécanique dans les années cinquante et le développement des soins intensifs dans les années soixante ont permis à de nombreux patients de survivre à de graves lésions ... [more ▼]

L’apparition de la ventilation mécanique dans les années cinquante et le développement des soins intensifs dans les années soixante ont permis à de nombreux patients de survivre à de graves lésions cérébrales. Bien que ces avancées technologiques soient étonnantes, de nombreux patients vont alors se retrouver dans des états cliniques critiques peu rencontrés auparavant (1). L’impact éthique de ces états d’inconscience se reflète lors de la rédaction des premiers comités de bioéthique et lors de l’apparition du concept d’acharnement thérapeutique. En 1968, le comité spécial de l’école médicale de Harvard a publié un article essentiel redéfinissant la mort comme étant un coma irréversible et une perte permanente de toutes les fonctions cérébrales (2). Le comité, composé de dix médecins, d’un théologien, d’un avocat et d’un historien des sciences, a débattu des questions médicales, juridiques et sociétales quant à la prise en charge des patients en mort cérébrale. Nous donnerons ici un bref aperçu des principales questions éthiques liées à la notion de conscience et à la prise en charge médicale des patients atteints de troubles de la conscience (TDC) tels que le coma, l’état végétatif et l’état de conscience minimale. Nous mettrons également l’accent sur le problème de la gestion de la douleur et des prises de décision en fin de vie. [less ▲]

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See detailHypnotic modulation of resting state fMRI default mode and extrinsic network connectivity
Demertzi, Athina ULg; Soddu, Andrea ULg; FAYMONVILLE, Marie-Elisabeth ULg et al

in Progress in Brain Research (2011), 193

Resting state fMRI (functional magnetic resonance imaging) acquisitions are characterized by low-frequency spontaneous activity in a default mode network (encompassing medial brain areas and linked to ... [more ▼]

Resting state fMRI (functional magnetic resonance imaging) acquisitions are characterized by low-frequency spontaneous activity in a default mode network (encompassing medial brain areas and linked to self-related processes) and an anticorrelated “extrinsic” system (encompassing lateral frontoparietal areas and modulated via external sensory stimulation). In order to better determine the functional contribution of these networks to conscious awareness, we here sought to transiently modulate their relationship by means of hypnosis. We used independent component analysis (ICA) on resting state fMRI acquisitions during normal wakefulness, under hypnotic state, and during a control condition of autobiographical mental imagery. As compared to mental imagery, hypnosis-induced modulation of resting state fMRI networks resulted in a reduced “extrinsic” lateral frontoparietal cortical connectivity, possibly reflecting a decreased sensory awareness. The default mode network showed an increased connectivity in bilateral angular and middle frontal gyri, whereas its posterior midline and parahippocampal structures decreased their connectivity during hypnosis, supposedly related to an altered “self” awareness and posthypnotic amnesia. In our view, fMRI resting state studies of physiological (e.g., sleep or hypnosis), pharmacological (e.g., sedation or anesthesia), and pathological modulation (e.g., coma or related states) of “intrinsic” default mode and anticorrelated “extrinsic” sensory networks, and their interaction with other cerebral networks, will further improve our understanding of the neural correlates of subjective awareness. [less ▲]

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See detailWhen the nursing workload measurement among comatose patients becomes a reality …
THONON, Olivier ULg; BOULANGER, Jean-Marie ULg; BAKAY, Tahar ULg et al

Poster (2011, May)

The neurologic unit of the Academic Hospital of Liège is composed of 30 beds. This is one of reference's centers for detection and differentiation of the comatose patients. With the mediatization of the ... [more ▼]

The neurologic unit of the Academic Hospital of Liège is composed of 30 beds. This is one of reference's centers for detection and differentiation of the comatose patients. With the mediatization of the Pr S. Laureys's findings, our reference's center accommodate more and more comatose patients from different European countries. With the arrival and the increase of these comatose patients, the nurses had the feeling of an increase workload by report to all others neurologic patients. The purpose of this overview is initially to be able to measure the nursing workload among comatose patients and to demonstrate that this one, within a neurology unit of an academic Belgian hospital, is heavier than that of other patients suffering from neurologic affections. [less ▲]

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See detailThe ethics in disorders of consciousness
Demertzi, Athina ULg; LAUREYS, Steven ULg; Bruno, Marie-Aurélie ULg

in Vincent, J. L. (Ed.) Annual Update in Intensive Care and Emergency Medicine (2011)

The introduction of the mechanical ventilator in the 1950s and the development of intensive care in the 1960s permitted many patients to sustain their vegetative functions and survive severe injuries ... [more ▼]

The introduction of the mechanical ventilator in the 1950s and the development of intensive care in the 1960s permitted many patients to sustain their vegetative functions and survive severe injuries. Despite such advances, in many cases patients were found to suffer from altered states of consciousness which had never been encountered before as these patients would normally have died from apnea [1]. The imminent ethical impact of these profound states of unconsciousness was reflected in the composition of the first bioethical committees discussing the redefinition of life and the concept of therapeutic obstinacy. In 1968, the Ad Hoc Committee of Harvard Medical School published a milestone paper for the redefinition of death as irreversible coma and brain failure [2]. The committee was comprised of ten physicians, a theologian, a lawyer and a historian of science, betokening the medical, legal and societal debates that were to follow. We will here give a brief overview of some ethical issues related to the concept of consciousness and the medical management of patients with disorders of consciousness, such as comatose, vegetative and minimally conscious states that may be encountered in the intensive care setting. We will emphasize the problem of pain management and end-of life decision-making. [less ▲]

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See detailResting-state activity in the tinnitus brain
Maudoux, Audrey ULg; LEFEBVRE, Philippe ULg; CABAY, Jean-Evrard ULg et al

Conference (2011, March)

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See detailA survey on self-assessed well-being in a cohort of chronic locked-in syndrome patients: happy majority, miserable minority
Bruno, Marie-Aurélie ULg; Bernheim, Jan; LEDOUX, Didier ULg et al

in BMJ Open (2011), 1

Objectives Locked-in syndrome (LIS) consists of anarthria and quadriplegia while consciousness is preserved. Classically, vertical eye movements or blinking allow coded communication. Given appropriate ... [more ▼]

Objectives Locked-in syndrome (LIS) consists of anarthria and quadriplegia while consciousness is preserved. Classically, vertical eye movements or blinking allow coded communication. Given appropriate medical care, patients can survive for decades. We studied the self-reported quality of life in chronic LIS patients.Design 168 LIS members of the French Association for LIS were invited to answer a questionnaire on medical history, current status and end-of-life issues. They self-assessed their global subjective well-being with the Anamnestic Comparative Self-Assessment (ACSA) scale, whose +5 and −5 anchors were their memories of the best period in their life before LIS and their worst period ever, respectively.Results 91 patients (54%) responded and 26 were excluded because of missing data on quality of life. 47 patients professed happiness (median ACSA +3) and 18 unhappiness (median ACSA −4). Variables associated with unhappiness included anxiety and dissatisfaction with mobility in the community, recreational activities and recovery of speech production. A longer time in LIS was correlated with happiness. 58% declared they did not wish to be resuscitated in case of cardiac arrest and 7% expressed a wish for euthanasia.Conclusions Our data stress the need for extra palliative efforts directed at mobility and recreational activities in LIS and the importance of anxiolytic therapy. Recently affected LIS patients who wish to die should be assured that there is a high chance they will regain a happy meaningful life. End-of-life decisions, including euthanasia, should not be avoided, but a moratorium to allow a steady state to be reached should be proposed. [less ▲]

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See detailNeural plasticity lessons from disorders of consciousness
Demertzi, Athina ULg; Schnakers, Caroline ULg; Soddu, Andrea ULg et al

in Frontiers in Psychology (2011), 1

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 ... [more ▼]

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). [less ▲]

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See detailTwo distinct neuronal networks mediate the awareness of environment and of self
Vanhaudenhuyse, Audrey ULg; Demertzi, Athina ULg; Schabus, Manuel et al

in Journal of Cognitive Neuroscience (2011), 23(3), 570-578

Evidence from functional neuroimaging studies on resting state suggests that there are two distinct anticorrelated cortical systems that mediate conscious awareness: an "extrinsic" system that encompasses ... [more ▼]

Evidence from functional neuroimaging studies on resting state suggests that there are two distinct anticorrelated cortical systems that mediate conscious awareness: an "extrinsic" system that encompasses lateral fronto-parietal areas and has been linked with processes of external input (external awareness), and an "intrinsic" system which encompasses mainly medial brain areas and has been associated with internal processes (internal awareness). The aim of our study was to explore the neural correlates of resting state by providing behavioral and neuroimaging data from healthy volunteers. With no a priori assumptions, we first determined behaviorally the relationship between external and internal awareness in 31 subjects. We found a significant anticorrelation between external and internal awareness with a mean switching frequency of 0.05 Hz (range: 0.01-0.1 Hz). Interestingly, this frequency is similar to BOLD fMRI slow oscillations. We then evaluated 22 healthy volunteers in an fMRI paradigm looking for brain areas where BOLD activity correlated with "internal" and "external" scores. Activation of precuneus/posterior cingulate, anterior cingulate/mesiofrontal cortices, and parahippocampal areas ("intrinsic system") was linearly linked to intensity of internal awareness, whereas activation of lateral fronto-parietal cortices ("extrinsic system") was linearly associated with intensity of external awareness. [less ▲]

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See detailAttitudes towards end-of-life issues in disorders of consciousness : a European survey
Demertzi, Athina ULg; LEDOUX, Didier ULg; Bruno, Marie-Aurélie ULg et al

in Journal of Neurology (2011), 258

Previous European surveys showed the support of healthcare professionals for treatment withdrawal [i.e., artificial nutrition and hydration (ANH) in chronic vegetative state (VS) patients]. The recent ... [more ▼]

Previous European surveys showed the support of healthcare professionals for treatment withdrawal [i.e., artificial nutrition and hydration (ANH) in chronic vegetative state (VS) patients]. The recent definition of minimally conscious state (MCS), and possibly research advances (e.g., functional neuroimaging), may have lead to uncertainty regarding potential residual perception and may have influenced opinions of healthcare professionals. The aim of the study was to update the end-of-life attitudes towards VS and to determine the end-of-life attitudes towards MCS. A 16-item questionnaire related to consciousness, pain and end-of-life issues in chronic (i.e., >1 year) VS and MCS and locked-in syndrome was distributed among attendants of medical and scientific conferences around Europe (n = 59). During a lecture, the items were explained orally to the attendants who needed to provide written yes/no responses. Chi-square tests and logistic regression analyses identified differences and associations for age, European region, religiosity, profession, and gender. We here report data on items concerning end-of-life issues on chronic VS and MCS. Responses were collected from 2,475 participants. For chronic VS (>1 year), 66% of healthcare professionals agreed to withdraw treatment and 82% wished not to be kept alive (P < 0.001). For chronic MCS (>1 year), less attendants agreed to withdraw treatment (28%, P < 0.001) and wished not to be kept alive (67%, P < 0.001). MCS was considered worse than VS for the patients in 54% and for their families in 42% of the sample. Respondents’ opinions were associated with geographic region and religiosity. Our data show that end-of-life opinions differ for VS as compared to MCS. The introduction of the diagnostic criteria for MCS has not substantially changed the opinions on end-of-life issues on permanent VS. Additionally, the existing legal ambiguity around MCS may have influenced the audience to draw a line between expressing preferences for self versus others, by implicitly recognizing that the latter could be a step on the slippery slope to legalize euthanasia. Given the observed individual variability, we stress the importance of advance directives and identification of proxies when discussing end-of-life issues in patients with disorders of consciousness. [less ▲]

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See detailAutomated EEG entropy measurements in coma, vegetative state/unresponsive wakefulness syndrome and minimally conscious state
Gosseries, Olivia ULg; Schnakers, Caroline ULg; LEDOUX, Didier ULg et al

in Functional Neurology (2011), 36

Monitoring the level of consciousness in brain injured patients with disorders of consciousness is crucial as it provides diagnostic and prognostic information. Behavioral assessment remains the gold ... [more ▼]

Monitoring the level of consciousness in brain injured patients with disorders of consciousness is crucial as it provides diagnostic and prognostic information. Behavioral assessment remains the gold standard for assessing consciousness but previous studies have shown a high rate of misdiagnosis. This study aimed to investigate the usefulness of electroencephalography (EEG) entropy measurements in differentiating unconscious (coma or vegetative) from minimally conscious patients. Left fronto-temporal EEG recordings (10-minute resting state epochs) were prospectively obtained in 56 patients and 16 age-matched healthy volunteers. Patients were assessed in the acute (≤1 month post-injury;n=29) or chronic (>1 month post-injury; n=27) stage. The etiology was traumatic in 23 patients. Automated online EEG entropy calculations (providing an arbitrary value ranging from 0 to 91) were compared with behavioral assessments (Coma Recovery Scale-Revised) and outcome. EEG entropy correlated with Coma Recovery Scale total scores (r=0.49). Mean EEG entropy values were higher in minimally conscious (73±19; mean and standard deviation) than in vegetative/unresponsive wakefulness syndrome patients (45±28). Receiver operating characteristic analysis revealed an entropy cut-off value of 52 differentiating acute unconscious from minimally conscious patients (sensitivity 89% and specificity 90%). In chronic patients, entropy measurements offered no reliable diagnostic information. EEG entropy measurements did not allow prediction of outcome. User-independent time-frequency balanced spectral EEG entropy measurements seem to constitute an interesting diagnostic – albeit not prognostic – tool for assessing neural network complexity in disorders of consciousness in the acute setting. Future studies are needed before using this tool in routine clinical practice, and these should seek to improve automated EEG quantification paradigms in order to reduce the remaining false negative and false positive findings. [less ▲]

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