Bedside detection of awareness in the vegetative state: a cohort study.
; ; Chatelle, Camille et al
in Lancet (2011), 378(9809), 2088-94
BACKGROUND: Patients diagnosed as vegetative have periods of wakefulness, but seem to be unaware of themselves or their environment. Although functional MRI (fMRI) studies have shown that some of these ... [more ▼]
BACKGROUND: Patients diagnosed as vegetative have periods of wakefulness, but seem to be unaware of themselves or their environment. Although functional MRI (fMRI) studies have shown that some of these patients are consciously aware, issues of expense and accessibility preclude the use of fMRI assessment in most of these individuals. We aimed to assess bedside detection of awareness with an electroencephalography (EEG) technique in patients in the vegetative state. METHODS: This study was undertaken at two European centres. We recruited patients with traumatic brain injury and non-traumatic brain injury who met the Coma Recovery Scale-Revised definition of vegetative state. We developed a novel EEG task involving motor imagery to detect command-following--a universally accepted clinical indicator of awareness--in the absence of overt behaviour. Patients completed the task in which they were required to imagine movements of their right-hand and toes to command. We analysed the command-specific EEG responses of each patient for robust evidence of appropriate, consistent, and statistically reliable markers of motor imagery, similar to those noted in healthy, conscious controls. FINDINGS: We assessed 16 patients diagnosed in the vegetative state, and 12 healthy controls. Three (19%) of 16 patients could repeatedly and reliably generate appropriate EEG responses to two distinct commands, despite being behaviourally entirely unresponsive (classification accuracy 61-78%). We noted no significant relation between patients' clinical histories (age, time since injury, cause, and behavioural score) and their ability to follow commands. When separated according to cause, two (20%) of the five traumatic and one (9%) of the 11 non-traumatic patients were able to successfully complete this task. INTERPRETATION: Despite rigorous clinical assessment, many patients in the vegetative state are misdiagnosed. The EEG method that we developed is cheap, portable, widely available, and objective. It could allow the widespread use of this bedside technique for the rediagnosis of patients who behaviourally seem to be entirely vegetative, but who might have residual cognitive function and conscious awareness. FUNDING: Medical Research Council, James S McDonnell Foundation, Canada Excellence Research Chairs Program, European Commission, Fonds de la Recherche Scientifique, Mind Science Foundation, Belgian French-Speaking Community Concerted Research Action, University Hospital of Liege, University of Liege. [less ▲]Detailed reference viewed: 6 (0 ULg)
Comparison of the Full Outline of UnResponsiveness and Glasgow Liege Scale/Glasgow Coma Scale in an Intensive Care Unit Population.
Bruno, Marie-Aurélie ; LEDOUX, Didier ; LAMBERMONT, Bernard 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 ▲]Detailed reference viewed: 73 (4 ULg)
Metabolic activity in external and internal awareness networks in severely brain damaged patients
Thibaut, Aurore ; Bruno, Marie-Aurélie ; Chatelle, Camille et al
Poster (2011)Detailed reference viewed: 10 (0 ULg)
Resting state activity in patients with disorders of consciousness.
Soddu, Andrea ; Vanhaudenhuyse, Audrey ; 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 ▲]Detailed reference viewed: 76 (16 ULg)
Changes in fMRI resting state activity during propofol-induced unconsciousness.
; Guldenmund, Justus Pieter ; Demertzi, Athina et al
Poster (2011)Detailed reference viewed: 19 (2 ULg)
Resting state brain connectivity during Propofol sedation and recovery in healthy subjects: implications for sedation of patients with disorders of consciousness.
Guldenmund, Justus Pieter ; Boveroux, Pierre ; et al
Poster (2011)Detailed reference viewed: 17 (2 ULg)
Brain functional integration decreases during propofol-induced loss of consciousness.
Schrouff, Jessica ; ; Boly, Mélanie et al
in NeuroImage (2011), 57(1), 198-205
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 ▲]Detailed reference viewed: 112 (35 ULg)
Propofol anesthesia and sleep: a high-density EEG study.
; Bruno, Marie-Aurélie ; et al
in Sleep (2011), 34(3), 283-91
STUDY OBJECTIVES: The electrophysiological correlates of anesthetic sedation remain poorly understood. We used high-density electroencephalography (hd-EEG) and source modeling to investigate the cortical ... [more ▼]
STUDY OBJECTIVES: The electrophysiological correlates of anesthetic sedation remain poorly understood. We used high-density electroencephalography (hd-EEG) and source modeling to investigate the cortical processes underlying propofol anesthesia and compare them to sleep. DESIGN: 256-channel EEG recordings in humans during propofol anesthesia. SETTING: Hospital operating room. PATIENTS OR PARTICIPANTS: 8 healthy subjects (4 males) INTERVENTIONS: N/A MEASUREMENTS AND RESULTS: Initially, propofol induced increases in EEG power from 12-25 Hz. Loss of consciousness (LOC) was accompanied by the appearance of EEG slow waves that resembled the slow waves of NREM sleep. We compared slow waves in propofol to slow waves recorded during natural sleep and found that both populations of waves share similar cortical origins and preferentially propagate along the mesial components of the default network. However, propofol slow waves were spatially blurred compared to sleep slow waves and failed to effectively entrain spindle activity. Propofol also caused an increase in gamma (25-40 Hz) power that persisted throughout LOC. Source modeling analysis showed that this increase in gamma power originated from the anterior and posterior cingulate cortices. During LOC, we found increased gamma functional connectivity between these regions compared to the wakefulness. CONCLUSIONS: Propofol anesthesia is a sleep-like state and slow waves are associated with diminished consciousness even in the presence of high gamma activity. CITATION: Murphy M; Bruno MA; Riedner BA; Boveroux P; Noirhomme Q; Landsness EC; Brichant JF; Phillips C; Massimini M; Laureys S; Tononi G; Boly M. Propofol anesthesia and sleep: a high-density EEG study. SLEEP 2011;34(3):283-291. [less ▲]Detailed reference viewed: 41 (8 ULg)
Imagerie fonctionnelle et états de conscience altérée
Vanhaudenhuyse, Audrey ; Boly, Mélanie ; Bruno, Marie-Aurélie et al
in Schnakers, Caroline; LAUREYS, Steven (Eds.) Coma et états de conscience altérée (2011)Detailed reference viewed: 20 (1 ULg)
La neuro-imagerie: un outil diagnostique des etats de conscience alteree.
Thonnard, Marie ; Boly, Mélanie ; et al
in Medecine Sciences : M/S (2011), 27(1), 77-81
Vegetative and minimally conscious states diagnosis remained a major clinical challenge. New paradigms such as measurement of the global cerebral metabolism, the structural and functional integrity of ... [more ▼]
Vegetative and minimally conscious states diagnosis remained a major clinical challenge. New paradigms such as measurement of the global cerebral metabolism, the structural and functional integrity of fronto-parietal network, or the spontaneous activity in resting state have been shown to be helpful to disentangle vegetative from minimally conscious patients. Active neuroimagery paradigms also allow detecting voluntary and conscious activity in non-communicative patients. The implementation of these methods in clinical routine could permit to reduce the current high rate of misdiagnosis (40%). [less ▲]Detailed reference viewed: 71 (6 ULg)
From unresponsive wakefulness to minimally conscious PLUS and functional locked-in syndromes: recent advances in our understanding of disorders of consciousness.
Bruno, Marie-Aurélie ; Vanhaudenhuyse, Audrey ; Thibaut, Aurore et al
in Journal of Neurology (2011), 258(7), 1373-84
Functional neuroimaging and electrophysiology studies are changing our understanding of patients with coma and related states. Some severely brain damaged patients may show residual cortical processing in ... [more ▼]
Functional neuroimaging and electrophysiology studies are changing our understanding of patients with coma and related states. Some severely brain damaged patients may show residual cortical processing in the absence of behavioural signs of consciousness. Given these new findings, the diagnostic errors and their potential effects on treatment as well as concerns regarding the negative associations intrinsic to the term vegetative state, the European Task Force on Disorders of Consciousness has recently proposed the more neutral and descriptive term unresponsive wakefulness syndrome. When vegetative/unresponsive patients show minimal signs of consciousness but are unable to reliably communicate the term minimally responsive or minimally conscious state (MCS) is used. MCS was recently subcategorized based on the complexity of patients' behaviours: MCS+ describes high-level behavioural responses (i.e., command following, intelligible verbalizations or non-functional communication) and MCS- describes low-level behavioural responses (i.e., visual pursuit, localization of noxious stimulation or contingent behaviour such as appropriate smiling or crying to emotional stimuli). Finally, patients who show non-behavioural evidence of consciousness or communication only measurable via para-clinical testing (i.e., functional MRI, positron emission tomography, EEG or evoked potentials) can be considered to be in a functional locked-in syndrome. An improved assessment of brain function in coma and related states is not only changing nosology and medical care but also offers a better-documented diagnosis and prognosis and helps to further identify the neural correlates of human consciousness. [less ▲]Detailed reference viewed: 60 (6 ULg)
"Relevance vector machine" consciousness classifier applied to cerebral metabolism of vegetative and locked-in patients.
Phillips, Christophe ; Bruno, Marie-Aurélie ; Maquet, Pierre et al
in NeuroImage (2011), 56(2), 797808
The vegetative state is a devastating condition where patients awaken from their coma (i.e., open their eyes) but fail to show any behavioural sign of conscious awareness. Locked-in syndrome patients also ... [more ▼]
The vegetative state is a devastating condition where patients awaken from their coma (i.e., open their eyes) but fail to show any behavioural sign of conscious awareness. Locked-in syndrome patients also awaken from their coma and are unable to show any motor response to command (except for small eye movements or blinks) but recover full conscious awareness of self and environment. Bedside evaluation of residual cognitive function in coma survivors often is difficult because motor responses may be very limited or inconsistent. We here aimed to disentangle vegetative from "locked-in" patients by an automatic procedure based on machine learning using fluorodeoxyglucose PET data obtained in 37 healthy controls and in 13 patients in a vegetative state. Next, the trained machine was tested on brain scans obtained in 8 patients with locked-in syndrome. We used a sparse probabilistic Bayesian learning framework called "relevance vector machine" (RVM) to classify the scans. The trained RVM classifier, applied on an input scan, returns a probability value (p-value) of being in one class or the other, here being "conscious" or not. Training on the control and vegetative state groups was assessed with a leave-one-out cross-validation procedure, leading to 100% classification accuracy. When applied on the locked-in patients, all scans were classified as "conscious" with a mean p-value of .95 (min .85). In conclusion, even with this relatively limited data set, we could train a classifier distinguishing between normal consciousness (i.e., wakeful conscious awareness) and the vegetative state (i.e., wakeful unawareness). Cross-validation also indicated that the clinical classification and the one predicted by the automatic RVM classifier were in accordance. Moreover, when applied on a third group of "locked-in" consciously aware patients, they all had a strong probability of being similar to the normal controls, as expected. Therefore, RVM classification of cerebral metabolic images obtained in coma survivors could become a useful tool for the automated PET-based diagnosis of altered states of consciousness. [less ▲]Detailed reference viewed: 94 (15 ULg)
Attitudes towards end-of-life issues in disorders of consciousness : a European survey
Demertzi, Athina ; LEDOUX, Didier ; Bruno, Marie-Aurélie 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 ▲]Detailed reference viewed: 268 (11 ULg)
Electrophysiological correlates of behavioural changes in vigilance in vegetative state and minimally conscious state.
; Bruno, Marie-Aurélie ; Noirhomme, Quentin et al
in Brain : A Journal of Neurology (2011), 134(Pt 8), 2222-32
The existence of normal sleep in patients in a vegetative state is still a matter of debate. Previous electrophysiological sleep studies in patients with disorders of consciousness did not differentiate ... [more ▼]
The existence of normal sleep in patients in a vegetative state is still a matter of debate. Previous electrophysiological sleep studies in patients with disorders of consciousness did not differentiate patients in a vegetative state from patients in a minimally conscious state. Using high-density electroencephalographic sleep recordings, 11 patients with disorders of consciousness (six in a minimally conscious state, five in a vegetative state) were studied to correlate the electrophysiological changes associated with sleep to behavioural changes in vigilance (sustained eye closure and muscle inactivity). All minimally conscious patients showed clear electroencephalographic changes associated with decreases in behavioural vigilance. In the five minimally conscious patients showing sustained behavioural sleep periods, we identified several electrophysiological characteristics typical of normal sleep. In particular, all minimally conscious patients showed an alternating non-rapid eye movement/rapid eye movement sleep pattern and a homoeostatic decline of electroencephalographic slow wave activity through the night. In contrast, for most patients in a vegetative state, while preserved behavioural sleep was observed, the electroencephalographic patterns remained virtually unchanged during periods with the eyes closed compared to periods of behavioural wakefulness (eyes open and muscle activity). No slow wave sleep or rapid eye movement sleep stages could be identified and no homoeostatic regulation of sleep-related slow wave activity was observed over the night-time period. In conclusion, we observed behavioural, but no electrophysiological, sleep wake patterns in patients in a vegetative state, while there were near-to-normal patterns of sleep in patients in a minimally conscious state. These results shed light on the relationship between sleep electrophysiology and the level of consciousness in severely brain-damaged patients. We suggest that the study of sleep and homoeostatic regulation of slow wave activity may provide a complementary tool for the assessment of brain function in minimally conscious state and vegetative state patients. [less ▲]Detailed reference viewed: 35 (2 ULg)
Preserved feedforward but impaired top-down processes in the vegetative state.
Boly, Mélanie ; ; Gosseries, Olivia et al
in Science (2011), 332(6031), 858-62
Frontoparietal cortex is involved in the explicit processing (awareness) of stimuli. Frontoparietal activation has also been found in studies of subliminal stimulus processing. We hypothesized that an ... [more ▼]
Frontoparietal cortex is involved in the explicit processing (awareness) of stimuli. Frontoparietal activation has also been found in studies of subliminal stimulus processing. We hypothesized that an impairment of top-down processes, involved in recurrent neuronal message-passing and the generation of long-latency electrophysiological responses, might provide a more reliable correlate of consciousness in severely brain-damaged patients, than frontoparietal responses. We measured effective connectivity during a mismatch negativity paradigm and found that the only significant difference between patients in a vegetative state and controls was an impairment of backward connectivity from frontal to temporal cortices. This result emphasizes the importance of top-down projections in recurrent processing that involve high-order associative cortices for conscious perception. [less ▲]Detailed reference viewed: 52 (12 ULg)
Two distinct neuronal networks mediate the awareness of environment and of self
Vanhaudenhuyse, Audrey ; Demertzi, Athina ; 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 ▲]Detailed reference viewed: 167 (23 ULg)
Response to comment on "preserved feedforward but impaired top-down processes in the vegetative state".
Boly, Mélanie ; ; Gosseries, Olivia et al
in Science (2011), 334(6060), 1203
King et al. raise some technical issues about our recent study showing impaired top-down processes in the vegetative state. We welcome the opportunity to provide more details about our methods and results ... [more ▼]
King et al. raise some technical issues about our recent study showing impaired top-down processes in the vegetative state. We welcome the opportunity to provide more details about our methods and results and to resolve their concerns. We substantiate our interpretation of the results and provide a point-by-point response to the issues raised. [less ▲]Detailed reference viewed: 31 (2 ULg)