Steven Laureys

Publications

• 7.18

  Impact points

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

  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 in fast rhythms (from beta to gamma range), slow activity (from delta to alpha range) rises selectively ... [more] 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 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.
• 2.46

  Impact points

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

  A Maudoux, Ph Lefebvre, J-E Cabay, A Demertzi, A Vanhaudenhuyse, S Laureys, A Soddu

  Brain research. 05/2012;

  Thirteen chronic tinnitus patients and fifteen age-matched healthy controls were studied on a 3T MRI scanner during resting condition (i.e. eyes closed, no task performance). The auditory resting-state component was selected using an automatic component selection approach. Functional connectivity (c... [more] Thirteen chronic tinnitus patients and fifteen age-matched healthy controls were studied on a 3T MRI scanner during resting condition (i.e. eyes closed, no task performance). The auditory resting-state component was selected using an automatic component selection approach. Functional connectivity (correlations/anti-correlations) in the extracted network was portrayed by integrating the ICA approach with a graph theory method. Tinnitus and control groups showed different graph connectivity patterns. In the control group, the connectivity graph was divided into two distinct anti-correlated networks. The first one encompassed the auditory cortices and the insula. The second one encompassed frontoparietal and anterior cingulate cortices, brainstem, amygdala, basal ganglia/nucleus accumbens and parahippocampal regions. In the tinnitus group, only one of the two previous described networks was observed, encompassing the auditory cortices and the insula. Direct group comparison showed, in the tinnitus group, an increased functional connectivity between auditory cortices and left parahippocampal region surviving multiple comparisons. We investigated possible correlation between four tinnitus relevant measures (THI and TQ scores, tinnitus duration and tinnitus intensity during the scanning session) and connectivity pattern in the tinnitus population. We observed a significant positive correlation between the beta values of the posterior cingulate/precuneus region and the THI score. Our results show a modified functional connectivity pattern in tinnitus sufferers and highlight the role of the parahippocampal region in tinnitus physiopathology. They also point out the importance of the activity and connectivity pattern of the posterior cingulate cortex/precuneus region to the development of the tinnitus associated distress.
• 3.54

  Impact points

  What about Pain in Disorders of Consciousness?

  C Schnakers, C Chatelle, A Demertzi, S Majerus, S Laureys

  The AAPS journal. 04/2012;

  The management and treatment of acute pain is very difficult in non-communicative patients with disorders of consciousness (i.e., vegetative state/unresponsive wakefulness syndrome (VS/UWS) and minimally conscious state), creating an ethical dilemma for caregivers and an emotional burden among both ... [more] The management and treatment of acute pain is very difficult in non-communicative patients with disorders of consciousness (i.e., vegetative state/unresponsive wakefulness syndrome (VS/UWS) and minimally conscious state), creating an ethical dilemma for caregivers and an emotional burden among both relatives and caregivers. In this review, we summarize recent findings about the neural substrates of nociception and pain in VS/UWS patients as well as recent behavioral assessment methods of nociception specifically designed for patients in altered states of consciousness. We will finally discuss implications for pain treatment in these patients.

• Brain Connectivity in Disorders of Consciousness.

  Mélanie Boly, Marcello Massimini, Marta Isabel Garrido, Olivia Gosseries, Quentin Noirhomme, Steven Laureys, Andrea Soddu

  Brain connectivity. 04/2012;

  Abstract The last 10 years witnessed a considerable increase in our knowledge of brain function in survivors to severe brain injuries with disorders of consciousness (DOC). At the same time, a growing interest developed for the use of functional neuroimaging as a new diagnostic tool in these patient... [more] Abstract The last 10 years witnessed a considerable increase in our knowledge of brain function in survivors to severe brain injuries with disorders of consciousness (DOC). At the same time, a growing interest developed for the use of functional neuroimaging as a new diagnostic tool in these patients. In this context, particular attention has been devoted to connectivity studies-as these, more than measures of brain metabolism, may be more appropriate to capture the dynamics of large populations of neurons. Here, we will review the pros and cons of various connectivity methods as potential diagnostic tools in brain-damaged patients with DOC. We will also discuss the relevance of the study of the level versus the contents of consciousness in this context.
• 9.43

  Impact points

  Hierarchical clustering of brain activity during human nonrapid eye movement sleep.

  Mélanie Boly, Vincent Perlbarg, Guillaume Marrelec, Manuel Schabus, Steven Laureys, Julien Doyon, Mélanie Pélégrini-Issac, Pierre Maquet, Habib Benali

  Proceedings of the National Academy of Sciences of the United States of America. 03/2012;

  Consciousness is reduced during nonrapid eye movement (NREM) sleep due to changes in brain function that are still poorly understood. Here, we tested the hypothesis that impaired consciousness during NREM sleep is associated with an increased modularity of brain activity. Cerebral connectivity was q... [more] Consciousness is reduced during nonrapid eye movement (NREM) sleep due to changes in brain function that are still poorly understood. Here, we tested the hypothesis that impaired consciousness during NREM sleep is associated with an increased modularity of brain activity. Cerebral connectivity was quantified in resting-state functional magnetic resonance imaging times series acquired in 13 healthy volunteers during wakefulness and NREM sleep. The analysis revealed a modification of the hierarchical organization of large-scale networks into smaller independent modules during NREM sleep, independently from EEG markers of the slow oscillation. Such modifications in brain connectivity, possibly driven by sleep ultraslow oscillations, could hinder the brain's ability to integrate information and account for decreased consciousness during NREM sleep.
• 8.17

  Impact points

  Relationship between etiology and covert cognition in the minimally conscious state.

  D Cruse, S Chennu, C Chatelle, D Fernández-Espejo, T A Bekinschtein, J D Pickard, S Laureys, A M Owen

  Neurology. 02/2012; 78(11):816-22.

  Functional neuroimaging has shown that the absence of externally observable signs of consciousness and cognition in severely brain-injured patients does not necessarily indicate the true absence of such abilities. However, relative to traumatic brain injury, nontraumatic injury is known to be associ... [more] Functional neuroimaging has shown that the absence of externally observable signs of consciousness and cognition in severely brain-injured patients does not necessarily indicate the true absence of such abilities. However, relative to traumatic brain injury, nontraumatic injury is known to be associated with a reduced likelihood of regaining overtly measurable levels of consciousness. We investigated the relationships between etiology and both overt and covert cognitive abilities in a group of patients in the minimally conscious state (MCS). Twenty-three MCS patients (15 traumatic and 8 nontraumatic) completed a motor imagery EEG task in which they were required to imagine movements of their right-hand and toes to command. When successfully performed, these imagined movements appear as distinct sensorimotor modulations, which can be used to determine the presence of reliable command-following. The utility of this task has been demonstrated previously in a group of vegetative state patients. Consistent and robust responses to command were observed in the EEG of 22% of the MCS patients (5 of 23). Etiology had a significant impact on the ability to successfully complete this task, with 33% of traumatic patients (5 of 15) returning positive EEG outcomes compared with none of the nontraumatic patients (0 of 8). The overt behavioral signs of awareness (measured with the Coma Recovery Scale-Revised) exhibited by nontraumatic MCS patients appear to be an accurate reflection of their covert cognitive abilities. In contrast, one-third of a group of traumatically injured patients in the MCS possess a range of high-level cognitive faculties that are not evident from their overt behavior.
• 1.88

  Impact points

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

  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 have been identified recently. This study measured brain metabolism in both networks in patients with seve... [more] Objective: 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.
• 5.35

  Impact points

  Unresponsiveness ≠ Unconsciousness.

  Robert D Sanders, Giulio Tononi, Steven Laureys, Jamie W Sleigh

  Anesthesiology. 02/2012; 116(4):946-959.

  Consciousness is subjective experience. During both sleep and anesthesia, consciousness is common, evidenced by dreaming. A defining feature of dreaming is that, while conscious, we do not experience our environment; we are disconnected. Besides inducing behavioral unresponsiveness, a key goal of an... [more] Consciousness is subjective experience. During both sleep and anesthesia, consciousness is common, evidenced by dreaming. A defining feature of dreaming is that, while conscious, we do not experience our environment; we are disconnected. Besides inducing behavioral unresponsiveness, a key goal of anesthesia is to prevent the experience of surgery (connected consciousness), by inducing either unconsciousness or disconnection of consciousness from the environment. Review of the isolated forearm technique demonstrates that consciousness, connectedness, and responsiveness uncouple during anesthesia; in clinical conditions, a median 37% of patients demonstrate connected consciousness. We describe potential neurobiological constructs that can explain this phenomenon: during light anesthesia the subcortical mechanisms subserving spontaneous behavioral responsiveness are disabled but information integration within the corticothalamic network continues to produce consciousness, and unperturbed norepinephrinergic signaling maintains connectedness. These concepts emphasize the need for developing anesthetic regimens and depth of anesthesia monitors that specifically target mechanisms of consciousness, connectedness, and responsiveness.
• 1.88

  Impact points

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

  Thibaut, M. A. Bruno, C. Chatelle, O. Gosseries, A. Vanhaudenhuyse, A. Demertzi, C. Schnakers, M. Thonnard, V. Charland, C. Bernard, M. Bahri, C. Phillips, M. Boly, R. Hustinx, S. Laureys

  Journal of Rehabilitation Medicine. 02/2012;
• 9.49

  Impact points

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

  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, employing simple sensory stimulations or verbal commands, have proven useful in detecting higher order pro... [more] Patients surviving severe brain injury may regain consciousness without recovering their ability to understand, move and communicate. Recently, electrophysiological and neuroimaging approaches, employing simple sensory stimulations or verbal commands, have proven useful in detecting higher order processing and, in some cases, in establishing some degree of communication in brain-injured subjects with severe impairment of motor function. To complement these approaches, it would be useful to develop methods to detect recovery of consciousness in ways that do not depend on the integrity of sensory pathways or on the subject's ability to comprehend or carry out instructions. As suggested by theoretical and experimental work, a key requirement for consciousness is that multiple, specialized cortical areas can engage in rapid causal interactions (effective connectivity). Here, we employ transcranial magnetic stimulation together with high-density electroencephalography to evaluate effective connectivity at the bedside of severely brain injured, non-communicating subjects. In patients in a vegetative state, who were open-eyed, behaviourally awake but unresponsive, transcranial magnetic stimulation triggered a simple, local response indicating a breakdown of effective connectivity, similar to the one previously observed in unconscious sleeping or anaesthetized subjects. In contrast, in minimally conscious patients, who showed fluctuating signs of non-reflexive behaviour, transcranial magnetic stimulation invariably triggered complex activations that sequentially involved distant cortical areas ipsi- and contralateral to the site of stimulation, similar to activations we recorded in locked-in, conscious patients. Longitudinal measurements performed in patients who gradually recovered consciousness revealed that this clear-cut change in effective connectivity could occur at an early stage, before reliable communication was established with the subject and before the spontaneous electroencephalogram showed significant modifications. Measurements of effective connectivity by means of transcranial magnetic stimulation combined with electroencephalography can be performed at the bedside while by-passing subcortical afferent and efferent pathways, and without requiring active participation of subjects or language comprehension; hence, they offer an effective way to detect and track recovery of consciousness in brain-injured patients who are unable to exchange information with the external environment.
• 4.41

  Impact points

  Auditory resting-state network connectivity in tinnitus: a functional MRI study.

  Audrey Maudoux, Philippe Lefebvre, Jean-Evrard Cabay, Athena Demertzi, Audrey Vanhaudenhuyse, Steven Laureys, Andrea Soddu

  PloS one. 01/2012; 7(5):e36222.

  The underlying functional neuroanatomy of tinnitus remains poorly understood. Few studies have focused on functional cerebral connectivity changes in tinnitus patients. The aim of this study was to test if functional MRI "resting-state" connectivity patterns in auditory network differ betw... [more] The underlying functional neuroanatomy of tinnitus remains poorly understood. Few studies have focused on functional cerebral connectivity changes in tinnitus patients. The aim of this study was to test if functional MRI "resting-state" connectivity patterns in auditory network differ between tinnitus patients and normal controls. Thirteen chronic tinnitus subjects and fifteen age-matched healthy controls were studied on a 3 tesla MRI. Connectivity was investigated using independent component analysis and an automated component selection approach taking into account the spatial and temporal properties of each component. Connectivity in extra-auditory regions such as brainstem, basal ganglia/NAc, cerebellum, parahippocampal, right prefrontal, parietal, and sensorimotor areas was found to be increased in tinnitus subjects. The right primary auditory cortex, left prefrontal, left fusiform gyrus, and bilateral occipital regions showed a decreased connectivity in tinnitus. These results show that there is a modification of cortical and subcortical functional connectivity in tinnitus encompassing attentional, mnemonic, and emotional networks. Our data corroborate the hypothesized implication of non-auditory regions in tinnitus physiopathology and suggest that various regions of the brain seem involved in the persistent awareness of the phenomenon as well as in the development of the associated distress leading to disabling chronic tinnitus.
• 4.41

  Impact points

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

  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 directed functional (i.e., causal) connectivity as reflected in quantities such as 'integrated information&#... [more] Changes 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.
• 5.74

  Impact points

  Coma and consciousness: Paradigms (re)framed by neuroimaging.

  Steven Laureys, Nicholas D Schiff

  NeuroImage. 12/2011;

  The past 15years have provided an unprecedented collection of discoveries that bear upon our scientific understanding of recovery of consciousness in the human brain following severe brain damage. Highlighted among these discoveries are unique demonstrations that patients with little or no behaviora... [more] The past 15years have provided an unprecedented collection of discoveries that bear upon our scientific understanding of recovery of consciousness in the human brain following severe brain damage. Highlighted among these discoveries are unique demonstrations that patients with little or no behavioral evidence of conscious awareness may retain critical cognitive capacities and the first scientific demonstrations that some patients, with severely injured brains and very longstanding conditions of limited behavioral responsiveness, may nonetheless harbor latent capacities for significant recovery. Included among such capacities are particularly human functions of language and higher-level cognition that either spontaneously or through direct interventions may reemerge even at long time intervals or remain unrecognized. Collectively, these observations have reframed scientific inquiry and further led to important new insights into mechanisms underlying consciousness in the human brain. These studies support a model of consciousness as the emergent property of the collective behavior of widespread frontoparietal network connectivity modulated by specific forebrain circuit mechanisms. We here review these advances in measurement and the scientific and broader implications of this rapidly progressing field of research.
• 2.14

  Impact points

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

  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 and caregivers think from the armchair: they can only make assumptions about what it would be like to wa... [more] 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 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.
• 2.90

  Impact points

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

  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 that this entity can be subcategorized into MCS- (i.e., patients only showing nonreflex behavior such as v... [more] Patients in a minimally conscious state (MCS) show restricted signs of awareness but are unable to communicate. We assessed cerebral glucose metabolism in MCS patients and tested the hypothesis that this entity can be subcategorized into MCS- (i.e., patients only showing nonreflex behavior such as visual pursuit, localization of noxious stimulation and/or contingent behavior) and MCS+ (i.e., patients showing command following).Patterns of cerebral glucose metabolism were studied using [(18)F]-fluorodeoxyglucose-PET in 39 healthy volunteers (aged 46 ± 18 years) and 27 MCS patients of whom 13 were MCS- (aged 49 ± 19 years; 4 traumatic; 21 ± 23 months post injury) and 14 MCS+ (aged 43 ± 19 years; 5 traumatic; 19 ± 26 months post injury). Results were thresholded for significance at false discovery rate corrected p < 0.05.We observed a metabolic impairment in a bilateral subcortical (thalamus and caudate) and cortical (fronto-temporo-parietal) network in nontraumatic and traumatic MCS patients. Compared to MCS-, patients in MCS+ showed higher cerebral metabolism in left-sided cortical areas encompassing the language network, premotor, presupplementary motor, and sensorimotor cortices. A functional connectivity study showed that Broca's region was disconnected from the rest of the language network, mesiofrontal and cerebellar areas in MCS- as compared to MCS+ patients.The proposed subcategorization of MCS based on the presence or absence of command following showed a different functional neuroanatomy. MCS- is characterized by preserved right hemispheric cortical metabolism interpreted as evidence of residual sensory consciousness. MCS+ patients showed preserved metabolism and functional connectivity in language networks arguably reflecting some additional higher order or extended consciousness albeit devoid of clinical verbal or nonverbal expression.
• 30.76

  Impact points

  Bedside detection of awareness in the vegetative state: a cohort study.

  Damian Cruse, Srivas Chennu, Camille Chatelle, Tristan A Bekinschtein, Davinia Fernández-Espejo, John D Pickard, Steven Laureys, Adrian M Owen

  Lancet. 11/2011; 378(9809):2088-94.

  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 mos... [more] 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. 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. 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. 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. 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 Liège, University of Liège.
• 8.17

  Impact points

  I am conscious: Mr ASL says so.

  Caroline Schnakers, Steven Laureys, Steve Majerus

  Neurology. 09/2011; 77(16):1506-7.

  I am the only one to know that I am conscious. I can nevertheless interact with others using verbal communication or motor responses to let them know that I am. What would happen if, to some extent, I would know this, but I would be unable to express it? How would my surroundings know? Here is the c... [more] I am the only one to know that I am conscious. I can nevertheless interact with others using verbal communication or motor responses to let them know that I am. What would happen if, to some extent, I would know this, but I would be unable to express it? How would my surroundings know? Here is the challenge facing clinicians involved in the care of patients recovering from coma: differentiating reflex from voluntary activity, or, in other words, detecting consciousness in noncommunicative patients.
• 9.49

  Impact points

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

  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 not differentiate patients in a vegetative state from patients in a minimally conscious state. Using high-density e... [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.

• Influence of anesthesia on cerebral blood flow, cerebral metabolic rate, and brain functional connectivity.

  Vincent Bonhomme, Pierre Boveroux, Pol Hans, Jean François Brichant, Audrey Vanhaudenhuyse, Melanie Boly, Steven Laureys

  Current opinion in anaesthesiology. 07/2011; 24(5):474-9.

  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. Cerebral cortex is the primary target of the hypnotic effect of anestheti... [more] 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. 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. 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.
• 5.74

  Impact points

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

  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 propofol anesthesia is associated with a significant reduction in the capacity of the brain to integrate informa... [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.