Marie-Aurélie Bruno

Publications of Marie-Aurélie Bruno

• Connectivity Changes Underlying Spectral EEG Changes during Propofol-Induced Loss of Consciousness.

  Authors: Mélanie Boly, Rosalyn Moran, Michael Murphy, Pierre Boveroux, Marie-Aurélie Bruno, Quentin Noirhomme, Didier Ledoux, Vincent Bonhomme, Jean-François Brichant, Giulio Tononi, Steven Laureys, Karl Friston

  The Journal of neuroscience : the official journal of the Society for Neuroscience. 05/2012; 32(20):7082-7090.

  The mechanisms underlying anesthesia-induced loss of consciousness remain a matter of debate. Recent electrophysiological reports suggest that while initial propofol infusion provokes an increase inThe mechanisms underlying anesthesia-induced loss of consciousness remain a matter of debate. Recent electrophysiological reports suggest that while initial propofol infusion provokes an increase in fast rhythms (from beta to gamma range), slow activity (from delta to alpha range) rises selectively during loss of consciousness. Dynamic causal modeling was used to investigate the neural mechanisms mediating these changes in spectral power in humans. We analyzed source-reconstructed data from frontal and parietal cortices during normal wakefulness, propofol-induced mild sedation, and loss of consciousness. Bayesian model selection revealed that the best model for explaining spectral changes across the three states involved changes in corticothalamic interactions. Compared with wakefulness, mild sedation was accounted for by an increase in thalamic excitability, which did not further increase during loss of consciousness. In contrast, loss of consciousness per se was accompanied by a decrease in backward corticocortical connectivity from frontal to parietal cortices, while thalamocortical connectivity remained unchanged. These results emphasize the importance of recurrent corticocortical communication in the maintenance of consciousness and suggest a direct effect of propofol on cortical dynamics.

• Metabolic activity in external and internal awareness networks in severely brain-damaged patients.

  Authors: Aurore Thibaut, Marie-Aurélie Bruno, Camille Chatelle, Olivia Gosseries, Audrey Vanhaudenhuyse, Athena Demertzi, Caroline Schnakers, Marie Thonnard, Vanessa Charland-Verville, Claire Bernard, Mohamed Ali Bahri, Christophe Phillips, Mélanie Boly, Roland Hustinx, Steven Laureys

  Journal of rehabilitation medicine : official journal of the UEMS European Board of Physical and Rehabilitation Medicine. 02/2012;

  Objective: An extrinsic cerebral network (encompassing lateral frontoparietal cortices) related to external/sensory awareness and an intrinsic midline network related to internal/self-awareness haveObjective: An extrinsic cerebral network (encompassing lateral frontoparietal cortices) related to external/sensory awareness and an intrinsic midline network related to internal/self-awareness have been identified recently. This study measured brain metabolism in both networks in patients with severe brain damage. Design: Prospective [18F]-fluorodeoxyglucose-positron emission tomography and Coma Recovery Scale-Revised assessments in a university hospital setting. Subjects: Healthy volunteers and patients in vegetative state/unresponsive wakefulness syndrome (VS/UWS), minimally conscious state (MCS), emergence from MCS (EMCS), and locked-in syndrome (LIS). Results: A total of 70 patients were included in the study: 24 VS/UWS, 28 MCS, 10 EMCS, 8 LIS and 39 age-matched controls. VS/UWS showed metabolic dysfunction in extrinsic and intrinsic networks and thalami. MCS showed dysfunction mostly in intrinsic network and thalami. EMCS showed impairment in posterior cingulate/retrosplenial cortices. LIS showed dysfunction only in infratentorial regions. Coma Recovery Scale-Revised total scores correlated with metabolic activity in both extrinsic and part of the intrinsic network and thalami. Conclusion: Progressive recovery of extrinsic and intrinsic awareness network activity was observed in severely brain-damaged patients, ranging from VS/UWS, MCS, EMCS to LIS. The predominance of intrinsic network impairment in MCS could reflect altered internal/self-awareness in these patients, which is difficult to quantify at the bedside.

• Recovery of cortical effective connectivity and recovery of consciousness in vegetative patients.

  Authors: Mario Rosanova, Olivia Gosseries, Silvia Casarotto, Mélanie Boly, Adenauer G Casali, Marie-Aurélie Bruno, Maurizio Mariotti, Pierre Boveroux, Giulio Tononi, Steven Laureys, Marcello Massimini

  Brain : a journal of neurology. 01/2012;

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

• Granger causality analysis of steady-state electroencephalographic signals during propofol-induced anaesthesia.

  Authors: Adam B Barrett, Michael Murphy, Marie-Aurélie Bruno, Quentin Noirhomme, Mélanie Boly, Steven Laureys, Anil K Seth

  PloS one. 01/2012; 7(1):e29072.

  Changes in conscious level have been associated with changes in dynamical integration and segregation among distributed brain regions. Recent theoretical developments emphasize changes in directedChanges in conscious level have been associated with changes in dynamical integration and segregation among distributed brain regions. Recent theoretical developments emphasize changes in directed functional (i.e., causal) connectivity as reflected in quantities such as 'integrated information' and 'causal density'. Here we develop and illustrate a rigorous methodology for assessing causal connectivity from electroencephalographic (EEG) signals using Granger causality (GC). Our method addresses the challenges of non-stationarity and bias by dividing data into short segments and applying permutation analysis. We apply the method to EEG data obtained from subjects undergoing propofol-induced anaesthesia, with signals source-localized to the anterior and posterior cingulate cortices. We found significant increases in bidirectional GC in most subjects during loss-of-consciousness, especially in the beta and gamma frequency ranges. Corroborating a previous analysis we also found increases in synchrony in these ranges; importantly, the Granger causality analysis showed higher inter-subject consistency than the synchrony analysis. Finally, we validate our method using simulated data generated from a model for which GC values can be analytically derived. In summary, our findings advance the methodology of Granger causality analysis of EEG data and carry implications for integrated information and causal density theories of consciousness.

• From armchair to wheelchair: How patients with a locked-in syndrome integrate bodily changes in experienced identity.

  Authors: Marie-Christine Nizzi, Athena Demertzi, Olivia Gosseries, Marie-Aurélie Bruno, François Jouen, Steven Laureys

  Consciousness and cognition. 11/2011; 21(1):431-7.

  Different sort of people are interested in personal identity. Philosophers frequently ask what it takes to remain oneself. Caregivers imagine their patients' experience. But both philosophers andDifferent sort of people are interested in personal identity. Philosophers frequently ask what it takes to remain oneself. Caregivers imagine their patients' experience. But both philosophers and caregivers think from the armchair: they can only make assumptions about what it would be like to wake up with massive bodily changes. Patients with a locked-in syndrome (LIS) suffer a full body paralysis without cognitive impairment. They can tell us what it is like. Forty-four chronic LIS patients and 20 age-matched healthy medical professionals answered a 15-items questionnaire targeting: (A) global evaluation of identity, (B) body representation and (C) experienced meaning in life. In patients, self-reported identity was correlated with B and C. Patients differed with controls in C. These results suggest that the paralyzed body remains a strong component of patients' experienced identity, that patients can adjust to objectives changes perceived as meaningful and that caregivers fail in predicting patients' experience.

• Functional neuroanatomy underlying the clinical subcategorization of minimally conscious state patients.

  Authors: Marie-Aurélie Bruno, Steve Majerus, Mélanie Boly, Audrey Vanhaudenhuyse, Caroline Schnakers, Olivia Gosseries, Pierre Boveroux, Murielle Kirsch, Athena Demertzi, Claire Bernard, Roland Hustinx, Gustave Moonen, Steven Laureys

  Journal of neurology. 11/2011;

  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 thatPatients 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.

• Electrophysiological correlates of behavioural changes in vigilance in vegetative state and minimally conscious state.

  Authors: Eric Landsness, Marie-Aurélie Bruno, Quentin Noirhomme, Brady Riedner, Olivia Gosseries, Caroline Schnakers, Marcello Massimini, Steven Laureys, Giulio Tononi, Mélanie Boly

  Brain : a journal of neurology. 08/2011; 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 notThe 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.

• Brain functional integration decreases during propofol-induced loss of consciousness.

  Authors: Jessica Schrouff, Vincent Perlbarg, Mélanie Boly, Guillaume Marrelec, Pierre Boveroux, Audrey Vanhaudenhuyse, Marie-Aurélie Bruno, Steven Laureys, Christophe Phillips, Mélanie Pélégrini-Issac, Pierre Maquet, Habib Benali

  NeuroImage. 07/2011; 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 propofolConsciousness 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.

• From unresponsive wakefulness to minimally conscious PLUS and functional locked-in syndromes: recent advances in our understanding of disorders of consciousness.

  Authors: Marie-Aurélie Bruno, Audrey Vanhaudenhuyse, Aurore Thibaut, Gustave Moonen, Steven Laureys

  Journal of neurology. 06/2011; 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 corticalFunctional 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.

• Preserved feedforward but impaired top-down processes in the vegetative state.

  Authors: Melanie Boly, Marta Isabel Garrido, Olivia Gosseries, Marie-Aurélie Bruno, Pierre Boveroux, Caroline Schnakers, Marcello Massimini, Vladimir Litvak, Steven Laureys, Karl Friston

  Science (New York, N.Y.). 05/2011; 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 thatFrontoparietal 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.

• Comparison of the Full Outline of UnResponsiveness and Glasgow Liege Scale/Glasgow Coma Scale in an intensive care unit population.

  Authors: Marie-Aurélie Bruno, Didier Ledoux, Bernard Lambermont, François Damas, Caroline Schnakers, Audrey Vanhaudenhuyse, Olivia Gosseries, Steven Laureys

  Neurocritical care. 04/2011; 15(3):447-53.

  The Full Outline of UnResponsiveness (FOUR) has been proposed as an alternative for the Glasgow Coma Scale (GCS)/Glasgow Liège Scale (GLS) in the evaluation of consciousness in severely brain-damagedThe Full Outline of UnResponsiveness (FOUR) has been proposed as an alternative for the Glasgow Coma Scale (GCS)/Glasgow Liège 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. 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). 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. 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.

• [Neuroimaging technique: a diagnostic tool to detect altered states of consciousness].

  Authors: Marie Thonnard, Mélanie Boly, Marie-Aurélie Bruno, Camille Chatelle, Olivia Gosseries, Steven Laureys, Audrey Vanhaudenhuyse

  Médecine sciences : M/S. 02/2011; 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 integrityVegetative 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%).

• Assessment of consciousness with electrophysiological and neurological imaging techniques.

  Authors: Marie-Aurélie Bruno, Olivia Gosseries, Didier Ledoux, Roland Hustinx, Steven Laureys

  Current opinion in critical care. 01/2011; 17(2):146-51.

  Brain MRI (diffusion tensor imaging and spectroscopy) and functional neuroimaging (PET, functional MRI, EEG and evoked potential studies) are changing our understanding of patients with disorders ofBrain MRI (diffusion tensor imaging and spectroscopy) and functional neuroimaging (PET, functional MRI, EEG and evoked potential studies) are changing our understanding of patients with disorders of consciousness encountered after coma such as the 'vegetative' or minimally conscious states. Increasing evidence from functional neuroimaging and electrophysiology demonstrates some residual cognitive processing in a subgroup of patients who clinically fail to show any response to commands, leading to the recent proposal of 'unresponsive wakefulness syndrome' as an alternative name for patients previously coined 'vegetative' or 'apallic'. Consciousness can be viewed as the emergent property of the collective behavior of widespread thalamocortical frontoparietal network connectivity. Data from physiological, pharmacological and pathological alterations of consciousness provide evidence in favor of this hypothesis. Increasing our understanding of the neural correlates of consciousness is helping clinicians to do a better job in terms of diagnosis, prognosis and finally treatment and drug development for these severely brain-damaged patients. The current challenge remains to continue translating this research from the bench to the bedside. Only well controlled large multicentric neuroimaging and electrophysiology studies will enable to identify which paraclinical diagnostic or prognostic test is necessary for our routine evidence-based assessment of individuals with disorders of consciousness.

• Disorders of consciousness: what's in a name?

  Authors: Olivia Gosseries, Marie-Aurélie Bruno, Camille Chatelle, Audrey Vanhaudenhuyse, Caroline Schnakers, Andrea Soddu, Steven Laureys

  NeuroRehabilitation. 01/2011; 28(1):3-14.

  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 andFollowing 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 non-verbal 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 ICD-9-CM diagnosis code and MEDLINE MeSH 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.

• A survey on self-assessed well-being in a cohort of chronic locked-in syndrome patients: happy majority, miserable minority.

  Authors: Marie-Aurélie Bruno, Jan L Bernheim, Didier Ledoux, Frédéric Pellas, Athena Demertzi, Steven Laureys

  BMJ open. 01/2011; 1(1):e000039.

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

• Breakdown of within- and between-network resting state functional magnetic resonance imaging connectivity during propofol-induced loss of consciousness.

  Authors: Pierre Boveroux, Audrey Vanhaudenhuyse, Marie-Aurélie Bruno, Quentin Noirhomme, Séverine Lauwick, André Luxen, Christian Degueldre, Alain Plenevaux, Caroline Schnakers, Christophe Phillips, Jean-François Brichant, Vincent Bonhomme, Pierre Maquet, Michael D Greicius, Steven Laureys, Mélanie Boly

  Anesthesiology. 09/2010; 113(5):1038-53.

  Mechanisms of anesthesia-induced loss of consciousness remain poorly understood. Resting-state functional magnetic resonance imaging allows investigating whole-brain connectivity changes duringMechanisms of anesthesia-induced loss of consciousness remain poorly understood. Resting-state functional magnetic resonance imaging allows investigating whole-brain connectivity changes during pharmacological modulation of the level of consciousness. Low-frequency spontaneous blood oxygen level-dependent fluctuations were measured in 19 healthy volunteers during wakefulness, mild sedation, deep sedation with clinical unconsciousness, and subsequent recovery of consciousness. Propofol-induced decrease in consciousness linearly correlates with decreased corticocortical and thalamocortical connectivity in frontoparietal networks (i.e., default- and executive-control networks). Furthermore, during propofol-induced unconsciousness, a negative correlation was identified between thalamic and cortical activity in these networks. Finally, negative correlations between default network and lateral frontoparietal cortices activity, present during wakefulness, decreased proportionally to propofol-induced loss of consciousness. In contrast, connectivity was globally preserved in low-level sensory cortices, (i.e., in auditory and visual networks across sedation stages). This was paired with preserved thalamocortical connectivity in these networks. Rather, waning of consciousness was associated with a loss of cross-modal interactions between visual and auditory networks. Our results shed light on the functional significance of spontaneous brain activity fluctuations observed in functional magnetic resonance imaging. They suggest that propofol-induced unconsciousness could be linked to a breakdown of cerebral temporal architecture that modifies both within- and between-network connectivity and thus prevents communication between low-level sensory and higher-order frontoparietal cortices, thought to be necessary for perception of external stimuli. They emphasize the importance of thalamocortical connectivity in higher-order cognitive brain networks in the genesis of conscious perception.

• Visual fixation in the vegetative state: an observational case series PET study.

  Authors: Marie-Aurélie Bruno, Audrey Vanhaudenhuyse, Caroline Schnakers, Mélanie Boly, Olivia Gosseries, Athena Demertzi, Steve Majerus, Gustave Moonen, Roland Hustinx, Steven Laureys

  BMC neurology. 01/2010; 10:35.

  Assessment of visual fixation is commonly used in the clinical examination of patients with disorders of consciousness. However, different international guidelines seem to disagree whether fixationAssessment of visual fixation is commonly used in the clinical examination of patients with disorders of consciousness. However, different international guidelines seem to disagree whether fixation is compatible with the diagnosis of the vegetative state (i.e., represents "automatic" subcortical processing) or is a sufficient sign of consciousness and higher order cortical processing. We here studied cerebral metabolism in ten patients with chronic post-anoxic encephalopathy and 39 age-matched healthy controls. Five patients were in a vegetative state (without fixation) and five presented visual fixation but otherwise showed all criteria typical of the vegetative state. Patients were matched for age, etiology and time since insult and were followed by repeated Coma Recovery Scale-Revised (CRS-R) assessments for at least 1 year. Sustained visual fixation was considered as present when the eyes refixated a moving target for more than 2 seconds as defined by CRS-R criteria. Patients without fixation showed metabolic dysfunction in a widespread fronto-parietal cortical network (with only sparing of the brainstem and cerebellum) which was not different from the brain function seen in patients with visual fixation. Cortico-cortical functional connectivity with visual cortex showed no difference between both patient groups. Recovery rates did not differ between patients without or with fixation (none of the patients showed good outcome). Our findings suggest that sustained visual fixation in (non-traumatic) disorders of consciousness does not necessarily reflect consciousness and higher order cortical brain function.

• Neural plasticity lessons from disorders of consciousness.

  Authors: Athena Demertzi, Caroline Schnakers, Andrea Soddu, Marie-Aurélie Bruno, Olivia Gosseries, Audrey Vanhaudenhuyse, Steven Laureys

  Frontiers in psychology. 01/2010; 1:245.

  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 aCommunication 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).

• Locked-in syndrome in children: report of five cases and review of the literature.

  Authors: Marie-Aurélie Bruno, Caroline Schnakers, François Damas, Frédéric Pellas, Isabelle Lutte, Jan Bernheim, Steve Majerus, Gustave Moonen, Serge Goldman, Steven Laureys

  Pediatric neurology. 10/2009; 41(4):237-46.

  The locked-in syndrome is a rare neurologic disorder defined by (1) the presence of sustained eye opening; (2) preserved awareness; (3) aphonia or hypophonia; (4) quadriplegia or quadriparesis; andThe locked-in syndrome is a rare neurologic disorder defined by (1) the presence of sustained eye opening; (2) preserved awareness; (3) aphonia or hypophonia; (4) quadriplegia or quadriparesis; and (5) a primary mode of communication that uses vertical or lateral eye movement or blinking. Five cases are reported here, and previous literature is reviewed. According to the literature, the most common etiology of locked-in syndrome in children is ventral pontine stroke, most frequently caused by a vertebrobasilar artery thrombosis or occlusion. In terms of prognosis, 35% of pediatric locked-in syndrome patients experienced some motor recovery, 26% had good recovery, 23% died, and 16% remained quadriplegic and anarthric. These findings raise important ethical considerations in terms of quality of life and end-of-life decisions in such challenging cases.

• The nociception coma scale: A new tool to assess nociception in disorders of consciousness.

  Authors: Caroline Schnakers, Camille Chatelle, Audrey Vanhaudenhuyse, Steve Majerus, Didier Ledoux, Melanie Boly, Marie-Aurélie Bruno, Pierre Boveroux, Athena Demertzi, Gustave Moonen, Steven Laureys

  Pain. 10/2009;

  Assessing behavioral responses to nociception is difficult in severely brain-injured patients recovering from coma. We here propose a new scale developed for assessing nociception in vegetative (VS)Assessing behavioral responses to nociception is difficult in severely brain-injured patients recovering from coma. We here propose a new scale developed for assessing nociception in vegetative (VS) and minimally conscious (MCS) coma survivors, the Nociception Coma Scale (NCS), and explore its concurrent validity, inter-rater agreement and sensitivity. Concurrent validity was assessed by analyzing behavioral responses of 48 post-comatose patients to a noxious stimulation (pressure applied to the fingernail) (28 VS and 20 MCS; age range 20-82years; 17 of traumatic etiology). Patients' were assessed using the NCS and four other scales employed in non-communicative patients: the 'Neonatal Infant Pain Scale' (NIPS) and the 'Faces, Legs, Activity, Cry, Consolability' (FLACC) used in newborns; and the 'Pain Assessment In Advanced Dementia Scale' (PAINAD) and the 'Checklist of Non-verbal Pain Indicators' (CNPI) used in dementia. For the establishment of inter-rater agreement, fifteen patients were concurrently assessed by two examiners. Concurrent validity, assessed by Spearman rank order correlations between the NCS and the four other validated scales, was good. Cohen's kappa analyses revealed a good to excellent inter-rater agreement for the NCS total and subscore measures, indicating that the scale yields reproducible findings across examiners. Finally, a significant difference between NCS total scores was observed as a function of diagnosis (i.e., VS or MCS). The NCS constitutes a sensitive clinical tool for assessing nociception in severely brain-injured patients. This scale constitutes the first step to a better management of patients recovering from coma.