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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)

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 detailComparison of the Full Outline of UnResponsiveness and Glasgow Liege Scale/Glasgow Coma Scale in an Intensive Care Unit Population.
Bruno, Marie-Aurélie ULg; LEDOUX, Didier ULg; LAMBERMONT, Bernard ULg et al

in Neurocritical Care (2011), 15(3), 447-53

BACKGROUND: The Full Outline of UnResponsiveness (FOUR) has been proposed as an alternative for the Glasgow Coma Scale (GCS)/Glasgow Liege Scale (GLS) in the evaluation of consciousness in severely brain ... [more ▼]

BACKGROUND: The Full Outline of UnResponsiveness (FOUR) has been proposed as an alternative for the Glasgow Coma Scale (GCS)/Glasgow Liege Scale (GLS) in the evaluation of consciousness in severely brain-damaged patients. We compared the FOUR and GLS/GCS in intensive care unit patients who were admitted in a comatose state. METHODS: FOUR and GLS evaluations were performed in randomized order in 176 acutely (<1 month) brain-damaged patients. GLS scores were transformed in GCS scores by removing the GLS brainstem component. Inter-rater agreement was assessed in 20% of the studied population (N = 35). A logistic regression analysis adjusted for age, and etiology was performed to assess the link between the studied scores and the outcome 3 months after injury (N = 136). RESULTS: GLS/GCS verbal component was scored 1 in 146 patients, among these 131 were intubated. We found that the inter-rater reliability was good for the FOUR score, the GLS/GCS. FOUR, GLS/GCS total scores predicted functional outcome with and without adjustment for age and etiology. 71 patients were considered as being in a vegetative/unresponsive state based on the GLS/GCS. The FOUR score identified 8 of these 71 patients as being minimally conscious given that these patients showed visual pursuit. CONCLUSIONS: The FOUR score is a valid tool with good inter-rater reliability that is comparable to the GLS/GCS in predicting outcome. It offers the advantage to be performable in intubated patients and to identify non-verbal signs of consciousness by assessing visual pursuit, and hence minimal signs of consciousness (11% in this study), not assessed by GLS/GCS scales. [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 detailLinking sleep and general anesthesia mechanisms: this is no walkover
BONHOMME, Vincent ULg; BOVEROUX, Pierre ULg; Vanhaudenhuyse, Audrey ULg et al

in Acta Anaesthesiologica Belgica (2011), 62(3), 161-171

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See detailMultimodal neuroimaging in patients with disorders of consciousness showing "functional hemispherectomy".
Bruno, Marie-Aurélie ULg; Fernandez-Espejo, D.; Lehembre, Remy ULg et al

in Progress in Brain Research (2011), 193

Beside behavioral assessment of patients with disorders of consciousness, neuroimaging modalities may offer objective paraclinical markers important for diagnosis and prognosis. They provide information ... [more ▼]

Beside behavioral assessment of patients with disorders of consciousness, neuroimaging modalities may offer objective paraclinical markers important for diagnosis and prognosis. They provide information on the structural location and extent of brain lesions (e.g., morphometric MRI and diffusion tensor imaging (DTI-MRI) assessing structural connectivity) but also their functional impact (e.g., metabolic FDG-PET, hemodynamic fMRI, and EEG measurements obtained in "resting state" conditions). We here illustrate the role of multimodal imaging in severe brain injury, presenting a patient in unresponsive wakefulness syndrome (UWS; i.e., vegetative state, VS) and in a "fluctuating" minimally conscious state (MCS). In both cases, resting state FDG-PET, fMRI, and EEG showed a functionally preserved right hemisphere, while DTI showed underlying differences in structural connectivity highlighting the complementarities of these neuroimaging methods in the study of disorders of consciousness. [less ▲]

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See detailDisorders of consciousness: coma, vegetative and minimally conscious states
Gosseries, Olivia ULg; Vanhaudenhuyse, Audrey ULg; Bruno, Marie-Aurélie ULg et al

in D. Cvetkovic & I. Cosic (Ed.) States of Consciousness: Experimental Insights into Meditation, Waking, Sleep and Dreams (2011)

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See detailComment évaluer la conscience chez des patients sévèrement cérébro-lésés ?
Gosseries, Olivia ULg; Laureys, Steven ULg; Vanhaudenhuyse, Audrey ULg

in Lutte, Isabelle (Ed.) L’évaluation du traumatisme crânien (2011)

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See detailResting state activity in patients with disorders of consciousness.
Soddu, Andrea ULg; Vanhaudenhuyse, Audrey ULg; Demertzi, Athena et al

in Functional Neurology (2011), 26(1), 37-43

Recent advances in the study of spontaneous brain activity have demonstrated activity patterns that emerge with no task performance or sensory stimulation; these discoveries hold promise for the study of ... [more ▼]

Recent advances in the study of spontaneous brain activity have demonstrated activity patterns that emerge with no task performance or sensory stimulation; these discoveries hold promise for the study of higher-order associative network functionality. Additionally, such advances are argued to be relevant in pathological states, such as disorders of consciousness (DOC), i.e., coma, vegetative and minimally conscious states. Recent studies on resting state activity in DOC, measured with functional magnetic resonance imaging (fMRI) techniques, show that functional connectivity is disrupted in the task-negative or the default mode network. However, the two main approaches employed in the analysis of resting state functional connectivity data (i.e., hypothesis-driven seed-voxel and data-driven independent component analysis) present multiple methodological difficulties, especially in non-collaborative DOC patients. Improvements in motion artifact removal and spatial normalization are needed before fMRI resting state data can be used as proper biomarkers in severe brain injury. However, we anticipate that such developments will boost clinical resting state fMRI studies, allowing for easy and fast acquisitions and ultimately improve the diagnosis and prognosis in the absence of DOC patients' active collaboration in data acquisition. [less ▲]

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See detailFaisabilité d’une alimentation orale chez les patients avec troubles de la conscience
Maudoux, Audrey ULg; BREUSKIN, Ingrid ULg; Gosseries, Olivia ULg et al

in Schnakers, Caroline (Ed.) Coma et états de conscience altérée (2011)

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See detailInfluence of anesthesia on cerebral blood flow, cerebral metabolic rate, and brain functional connectivity.
BONHOMME, Vincent ULg; BOVEROUX, Pierre ULg; HANS, Pol ULg et al

in Current Opinion in Anaesthesiology (2011), 24(5), 474-9

PURPOSE OF REVIEW: To describe recent studies exploring brain function under the influence of hypnotic anesthetic agents, and their implications on the understanding of consciousness physiology and ... [more ▼]

PURPOSE OF REVIEW: To describe recent studies exploring brain function under the influence of hypnotic anesthetic agents, and their implications on the understanding of consciousness physiology and anesthesia-induced alteration of consciousness. RECENT FINDINGS: Cerebral cortex is the primary target of the hypnotic effect of anesthetic agents, and higher-order association areas are more sensitive to this effect than lower-order processing regions. Increasing concentration of anesthetic agents progressively attenuates connectivity in the consciousness networks, while connectivity in lower-order sensory and motor networks is preserved. Alteration of thalamic sub-cortical regulation could compromise the cortical integration of information despite preserved thalamic activation by external stimuli. At concentrations producing unresponsiveness, the activity of consciousness networks becomes anticorrelated with thalamic activity, while connectivity in lower-order sensory networks persists, although with cross-modal interaction alterations. SUMMARY: Accumulating evidence suggests that hypnotic anesthetic agents disrupt large-scale cerebral connectivity. This would result in an inability of the brain to generate and integrate information, while external sensory information is still processed at a lower order of complexity. [less ▲]

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See detailIdentifying the default-mode component in spatial IC analyses of patients with disorders of consciousness.
Soddu, Andrea ULg; Vanhaudenhuyse, Audrey ULg; Bahri, Mohamed Ali ULg et al

in Human Brain Mapping (2011)

Objectives:Recent fMRI studies have shown that it is possible to reliably identify the default-mode network (DMN) in the absence of any task, by resting-state connectivity analyses in healthy volunteers ... [more ▼]

Objectives:Recent fMRI studies have shown that it is possible to reliably identify the default-mode network (DMN) in the absence of any task, by resting-state connectivity analyses in healthy volunteers. We here aimed to identify the DMN in the challenging patient population of disorders of consciousness encountered following coma. Experimental design: A spatial independent component analysis-based methodology permitted DMN assessment, decomposing connectivity in all its different sources either neuronal or artifactual. Three different selection criteria were introduced assessing anticorrelation-corrected connectivity with or without an automatic masking procedure and calculating connectivity scores encompassing both spatial and temporal properties. These three methods were validated on 10 healthy controls and applied to an independent group of 8 healthy controls and 11 severely brain-damaged patients [locked-in syndrome (n = 2), minimally conscious (n = 1), and vegetative state (n = 8)]. Principal observations: All vegetative patients showed fewer connections in the default-mode areas, when compared with controls, contrary to locked-in patients who showed near-normal connectivity. In the minimally conscious-state patient, only the two selection criteria considering both spatial and temporal properties were able to identify an intact right lateralized BOLD connectivity pattern, and metabolic PET data suggested its neuronal origin. Conclusions: When assessing resting-state connectivity in patients with disorders of consciousness, it is important to use a methodology excluding non-neuronal contributions caused by head motion, respiration, and heart rate artifacts encountered in all studied patients. Hum Brain Mapp, 2011. (c) 2011 Wiley-Liss, Inc. [less ▲]

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See detailDisorders of consciousness: What's in a name?
Gosseries, Olivia ULg; Bruno, Marie-Aurélie ULg; Chatelle, Camille ULg et al

in NeuroRehabilitation (2011), 28

Following a coma, some patients may “awaken” without voluntary interaction or communication with the environment. More than 40 years ago this condition was coined coma vigil or apallic syndrome and later ... [more ▼]

Following a coma, some patients may “awaken” without voluntary interaction or communication with the environment. More than 40 years ago this condition was coined coma vigil or apallic syndrome and later became worldwide known as “persistent vegetative state”. About 10 years ago it became clear that some of these patients who failed to recover verbal or nonverbal communication did show some degree of consciousness – a condition called “minimally conscious state”. Some authors questioned the usefulness of differentiating unresponsive “vegetative” from minimally conscious patients but subsequent functional neuroimaging studies have since objectively demonstrated differences in residual cerebral processing and hence, we think, conscious awareness. These neuroimaging studies have also demonstrated that a small subset of unresponsive “vegetative” patients may show unambiguous signs of consciousness and command following inaccessible to bedside clinical examination. These findings, together with negative associations intrinsic to the term “vegetative state” as well as the diagnostic errors and their potential effect on the treatment and care for these patients gave rise to the recent proposal for an alternative neutral and more descriptive name: unresponsive wakefulness syndrome. We here give an overview of PET and (functional) MRI studies performed in these challenging patients and stress the need for a separate ICD9CM diagnosis code and MEDLINEMeSH entry for “minimally conscious state” as the lack of clear distinction between vegetative state/unresponsive wakefulness syndrome and minimally conscious state may encumber scientific studies in the field of disorders of consciousness. [less ▲]

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See detailBrain connectivity in pathological and pharmacological coma
Noirhomme, Quentin ULg; Soddu, Andrea ULg; Lehembre, Remy ULg et al

in Frontiers in Systems Neuroscience [=FNSYS] (2010), 4

Recent studies in patients with disorders of consciousness (DOC) tend to support the view that awareness is not related to activity in a single brain region but to thalamo-cortical connectivity in the ... [more ▼]

Recent studies in patients with disorders of consciousness (DOC) tend to support the view that awareness is not related to activity in a single brain region but to thalamo-cortical connectivity in the frontoparietal network. Functional neuroimaging studies have shown preserved albeit disconnected low-level cortical activation in response to external stimulation in patients in a “vegetative state” or unresponsive wakefulness syndrome. While activation of these “primary” sensory cortices does not necessarily reflect conscious awareness, activation in higher-order associative cortices in minimally conscious state patients seems to herald some residual perceptual awareness. PET studies have identified a metabolic dysfunction in a widespread frontoparietal “global neuronal workspace” in DOC patients including the midline default mode network (“intrinsic” system) and the lateral frontoparietal cortices or “extrinsic system.” Recent studies have investigated the relation of awareness to the functional connectivity within intrinsic and extrinsic networks, and with the thalami in both pathological and pharmacological coma. In brain damaged patients, connectivity in all default network areas was found to be non-linearly correlated with the degree of clinical consciousness impairment, ranging from healthy controls and locked-in syndrome to minimally conscious, vegetative, coma, and brain dead patients. Anesthesia-induced loss of consciousness was also shown to correlate with a global decrease in cortico-cortical and thalamo-cortical connectivity in both intrinsic and extrinsic networks, but not in auditory, or visual networks. In anesthesia, unconsciousness was also associated with a loss of cross-modal interactions between networks. These results suggest that conscious awareness critically depends on the functional integrity of thalamo-cortical and cortico-cortical frontoparietal connectivity within and between “intrinsic” and “extrinsic” brain networks. [less ▲]

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See detailChanges in functional interactions during anaesthesia-induced loss of consciousness
Schrouff, Jessica ULg; Perlbarg, Vincent; Boly, Mélanie ULg et al

Poster (2010, December 12)

Consciousness has been related to the amount of integrated information that the brain is able to generate. In this paper, we tested the hypothesis that the loss of consciousness caused by propofol ... [more ▼]

Consciousness has been related to the amount of integrated information that the brain is able to generate. In this paper, we tested the hypothesis that the loss of consciousness caused by propofol anesthesia is associated with a significant reduction in the capacity of the brain to integrate information. To assess the functional structure of the whole brain, functional integration and partial correlations were computed from fMRI data acquired from 18 healthy volunteers during resting wakefulness and propofol-induced deep sedation. Total integration was significantly reduced from wakefulness to deep sedation in the whole brain as well as within and between its constituent networks (or systems). Integration was systematically reduced within each system (i.e., brain or networks), as well as between networks. However, the ventral attentional network maintained interactions with most other networks during deep sedation. Partial correlations further suggested that functional connectivity was particularly affected between parietal areas and frontal or temporal regions during deep sedation. Our findings suggest that the breakdown in brain integration is the neural correlate of the loss of consciousness induced by propofol. They stress the important role played by parietal and frontal areas in the generation of consciousness. [less ▲]

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See detailNear-Death Experiences : Real or imagined memories?
Thonnard, Marie ULg; Laureys, Steven ULg; Brédart, Serge ULg et al

Poster (2010, September)

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See detailBrain-computer interface in disorders of consciousness: answering simple questions with a P3 speller
Noirhomme, Quentin ULg; Chatelle, Camille ULg; Kleih, Sonja et al

Poster (2010, June)

Objective: In the recovery from coma, the acquisition of command following represents an important milestone, indicating emergence from the vegetative state (Schnakers et al., 2009). In some patients ... [more ▼]

Objective: In the recovery from coma, the acquisition of command following represents an important milestone, indicating emergence from the vegetative state (Schnakers et al., 2009). In some patients, recovery of consciousness may precede motor recovery. Brain-computer interfaces (BCI) might permit these patients to show non-motor dependent signs of awareness and in a next step might enable communication. This study aimed at testing to what extent an EEG-based BCI could help detecting signs of awareness and communication in disorders of consciousness. We employed a P300 based BCI where healthy volunteers and patients with locked-in syndrome and in a minimally conscious state were asked to answer yes or no to simple questions by paying attention to one out of four auditorily presented stimuli (‘yes’, ‘no’, ‘stop’, ‘go’). Methods: We studied 13 patients with a minimally conscious state (MCS, 5 TBI – 8 anoxic, mean time post injury 70±109 months; mean age 42 ± 21) and 2 in pseudo-coma or locked in syndrome (LIS; brainstem stroke, time post injury 26 and 46 months; aged 63 and 29)) and 16 healthy controls (aged 45±19). Patients were evaluated using the Coma Recovery Scale Revised (CRS-R). An auditory P300 four choice speller paradigm (Furdea et al., 2009) based on the BCI2000 system (Schalk et al., 2004) was used. 16-Channel EEG was recorded using a g.tec USBAmp amplifier. A trial constituted of 15 presentation of four sounds the order of presentation being pseudo-randomized (sound duration: ~400ms; inter-stimulus interval: ~600ms). After a training session of 4 trials, patients and healthy subjects were required to answer 10 or 12 questions, respectively. Questions were of the following kind: “Is your name Quentin?”, “Is your mother’s name Dorothée?”. A stepwise linear discriminant analysis based on the training session was used to classify the data and to provide online feedback. Offline, all training and testing sequences were pooled. Sequences with artifacts were discarded and a leave-one-out approach was used to classify the data. Results: Healthy subjects presented a mean correct response rate of 73% online and 93% offline. Note that online classification failed for one control subject due to a presumed change in cognitive strategy between training and testing sessions. LIS patients showed a correct response rate of 30 and 60% (online) and 36 and 79% (offline). Three MCS patients had a correct response rate of ≥50% offline (10, 18, 0% online and 50, 53, 57% offline). Two of these three patients did not show any command following at the bedside. The 10 remaining MCS cases showed online and offline correct answers <50% (mean 33±9% online and 25±13% offline). Conclusion: Our auditory P300-based BCI permitted functional interactive communication in 15/16 controls (online) and in all offline. Our data obtained in patients with locked-in syndrome and disorders of consciousness demonstrate the potential clinical usefulness of the technique following coma but also show lower accuracy in patients as compared to healthy volunteers. This might be due to fluctuating attentional levels and exhaustibility in the MCS and to the suboptimal EEG recording quality due to movement, ocular and respiration artifacts in these challenging patients. Further algorithmic developments should include automatic artifact detection and single trial classification. Despite the need for further improvement in BCI devices adapted to post-coma patients, our results already indicate that MCS patients without any clinical sign of command-following can employ a yes-no speller offering the hope of functional interactive communication and a possibility for decision making and autonomy. Bibliography Furdea A, Halder S, Krusienski DJ, Bross D, Nijboer F, Birbaumer N, Kübler A, 2009, An auditory oddball (P300) spelling system for brain-computer interfaces, Psychophysiology. May; 46(3):617-25. Schalk G., McFarland D.J., Hinterberger T., Birbaumer N., and Wolpaw J.R. 2004, BCI2000: A General-Purpose Brain-Computer Interface (BCI) System, IEEE Trans Biomed Eng, 51(6). Schnakers C, Vanhaudenhuyse A, Giacino J, Ventura; Boly M, Majerus S, Moonen G, Laureys S, 2009, Diagnostic accuracy of the vegetative and minimally conscious state: Clinical consensus versus standardized neurobehavioral assessment, BMC Neurology, 9 (35). [less ▲]

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