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See detailDefault network connectivity reflects the level of consciousness in non-communicative brain-damaged patients.
Vanhaudenhuyse, Audrey ULg; Noirhomme, Quentin ULg; Tshibanda, Luaba ULg et al

in Brain : A Journal of Neurology (2010), 133(Pt 1), 161-71

The 'default network' is defined as a set of areas, encompassing posterior-cingulate/precuneus, anterior cingulate/mesiofrontal cortex and temporo-parietal junctions, that show more activity at rest than ... [more ▼]

The 'default network' is defined as a set of areas, encompassing posterior-cingulate/precuneus, anterior cingulate/mesiofrontal cortex and temporo-parietal junctions, that show more activity at rest than during attention-demanding tasks. Recent studies have shown that it is possible to reliably identify this network in the absence of any task, by resting state functional magnetic resonance imaging connectivity analyses in healthy volunteers. However, the functional significance of these spontaneous brain activity fluctuations remains unclear. The aim of this study was to test if the integrity of this resting-state connectivity pattern in the default network would differ in different pathological alterations of consciousness. Fourteen non-communicative brain-damaged patients and 14 healthy controls participated in the study. Connectivity was investigated using probabilistic independent component analysis, and an automated template-matching component selection approach. Connectivity in all default network areas was found to be negatively correlated with the degree of clinical consciousness impairment, ranging from healthy controls and locked-in syndrome to minimally conscious, vegetative then coma patients. Furthermore, precuneus connectivity was found to be significantly stronger in minimally conscious patients as compared with unconscious patients. Locked-in syndrome patient's default network connectivity was not significantly different from controls. Our results show that default network connectivity is decreased in severely brain-damaged patients, in proportion to their degree of consciousness impairment. Future prospective studies in a larger patient population are needed in order to evaluate the prognostic value of the presented methodology. [less ▲]

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See detailSleep in disorders of consciousness
Cologan, Victor ULg; Schabus, Manuel; LEDOUX, Didier ULg et al

in Sleep Medicine Reviews (2010), 14(2), 97-105

From a behavioral as well as neurobiological point of view, sleep and consciousness are intimately connected. A better understanding of sleep cycles and sleep architecture of patients suffering from ... [more ▼]

From a behavioral as well as neurobiological point of view, sleep and consciousness are intimately connected. A better understanding of sleep cycles and sleep architecture of patients suffering from disorders of consciousness (DOC) might therefore improve the clinical care for these patients as well as our understanding of the neural correlations of consciousness. Defining sleep in severely brain-injured patients is however problematic as both their electrophysiological and sleep patterns differ in many ways from healthy individuals. This paper discusses the concepts involved in the study of sleep of patients suffering from DOC and critically assesses the applicability of standard sleep criteria in these patients. <br /><br />The available literature on comatose and vegetative states as well as that on locked-in and related states following traumatic or non-traumatic severe brain injury will be reviewed. A wide spectrum of sleep disturbances ranging from almost normal patterns to severe loss and architecture disorganization are reported in cases of DOC and some patterns correlate with diagnosis and prognosis. At the present time the interactions of sleep and consciousness in brain-injured patients are a little studied subject but, the authors suggest, a potentially very interesting field of research. [less ▲]

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See detailDisorders of consciousness: Moving from passive to resting state and active paradigms
Bruno, Marie-Aurélie ULg; Soddu, Andrea ULg; Demertzi, Athina ULg et al

in Cognitive Neuroscience (2010), 1(1), 193203

Following coma, some patients will recover wakefulness without signs of consciousness (i.e., vegetative state) or may show nonreflexive movements but with no ability for functional communication (i.e ... [more ▼]

Following coma, some patients will recover wakefulness without signs of consciousness (i.e., vegetative state) or may show nonreflexive movements but with no ability for functional communication (i.e., minimally conscious state). Currently, there remains a high rate of misdiagnosis of the vegetative state. The increasing use of fMRI and EEG tools permits the clinical characterization of these patients to be improved. We first discuss “resting metabolism” and “passive activation” paradigms, used in neuroimaging and evoked potential studies, which merely identify neural activation reflecting “automatic” processing—that is, occurring without the patient’s willful intervention. Secondly, we present an alternative approach consisting of instructing subjects to imagine well-defined sensorymotor or cognitive-mental actions. This strategy reflects volitional neural activation and, hence, witnesses awareness. Finally, we present results on blood-oxgen-level-dependent “default mode network”/resting state studies that might be a promising tool in the diagnosis of these challenging patients. [less ▲]

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See detailAuditory P300 and the altered consciousness: detecting altered states of consciousness using the P300 speller
Lulé, D.; Kleih, S.; Chatelle, Camille ULg et al

in Proceedings of TOBI Workshop 2010: Integrating Brain-Computer Interfaces with Conventional Assistive Technology (2010)

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See detailLa Sensory Modality Assessment and Rehabilitation Technique (SMART) : une echelle comportementale d'evaluation et de revalidation pour des etats alteres de conscience.
Chatelle, Camille ULg; Schnakers, Caroline ULg; Bruno, Marie-Aurélie ULg et al

in Revue Neurologique (2010), 166(8-9), 675-82

INTRODUCTION: Difficulties in detecting bedside signs of consciousness in non-communicative patients still lead to a high rate of misdiagnosis illustrating the need to employ standardized behavioral ... [more ▼]

INTRODUCTION: Difficulties in detecting bedside signs of consciousness in non-communicative patients still lead to a high rate of misdiagnosis illustrating the need to employ standardized behavioral assessment scales. STATE OF ART: The Sensory Modality Assessment and Rehabilitation Technique (SMART) is a behavioral assessment scale of consciousness that assesses responses to multimodal sensory stimulation in disorders of consciousness. These stimulations can also be considered to have therapeutic value. PERSPECTIVES: We here review the different components and use of the SMART assessment and discuss its validity, reliability, and robustness in clinical practice. The scale has a high intra- and inter-observer reliability thanks to a detailed procedure description. However, in the absence of objective gold standards in the assessment of consciousness, it is currently difficult to make strong claims about its validity. A comparison between SMART and other standardized and validated coma-scales is proposed. CONCLUSION: In our view, SMART is an interesting tool for monitoring patients with altered states of consciousness subsequent to coma. Currently, we await studies on its concurrent validity as compared to other validated behavioral assessment scales and on the effect of SMART stimulations on patient outcome. [less ▲]

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See detailAssessment and detection of pain in noncommunicative severely brain-injured patients.
Schnakers, Caroline ULg; Chatelle, Camille ULg; Majerus, Steve ULg et al

in Expert Review of Neurotherapeutics (2010), 10(11), 1725-31

Detecting pain in severely brain-injured patients recovering from coma represents a real challenge. Patients with disorders of consciousness are unable to consistently or reliably communicate their ... [more ▼]

Detecting pain in severely brain-injured patients recovering from coma represents a real challenge. Patients with disorders of consciousness are unable to consistently or reliably communicate their feelings and potential perception of pain. However, recent studies suggest that patients in a minimally conscious state can experience pain to some extent. Pain monitoring in these patients is hence of medical and ethical importance. In this article, we will focus on the possible use of behavioral scales for the assessment and detection of pain in noncommunicative patients. [less ▲]

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See detailBreakdown of within- and between-network resting state functional magnetic resonance imaging connectivity during propofol-induced loss of consciousness.
Boveroux, Pierre ULg; Vanhaudenhuyse, Audrey ULg; Bruno, Marie-Aurélie ULg et al

in Anesthesiology (2010), 113(5), 1038-53

BACKGROUND: Mechanisms of anesthesia-induced loss of consciousness remain poorly understood. Resting-state functional magnetic resonance imaging allows investigating whole-brain connectivity changes ... [more ▼]

BACKGROUND: Mechanisms 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. [less ▲]

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See detailThe vegetative state.
Monti, Martin M; Laureys, Steven ULg; Owen, Adrian M

in BMJ (Clinical Research ed.) (2010), 341

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See detailAnterior cingulate activity and the self in disorders of consciousness.
Qin, Pengmin; Di, Haibo; Liu, Yijun et al

in Human Brain Mapping (2010), 31(12), 1993-2002

OBJECTIVES: The aim of this study was to investigate the relationship between medial cortical activation and the presence of self and consciousness in healthy subjects and patients with vegetative state ... [more ▼]

OBJECTIVES: The aim of this study was to investigate the relationship between medial cortical activation and the presence of self and consciousness in healthy subjects and patients with vegetative state and minimally conscious state using functional magnetic resonance imaging (fMRI). EXPERIMENT DESIGN: We first conducted two fMRI experiments in healthy subjects to identify brain regions specifically associated with self-perception through the use of different auditory stimuli that had different grades of self-relatedness. We then applied these regions as functional localizers to examine the relationship between neural activity changes during self-relatedness and consciousness level in the patients with disorders of consciousness (DOC). PRINCIPAL OBSERVATIONS: We demonstrated recruitment of various anterior medial cortical regions including the anterior cingulate cortex (ACC) in healthy subjects during auditory perception of self-related stimuli. We further showed that patients with DOC showed signal changes in the ACC during auditory perception of self-related stimuli. Finally, it was shown that these signal changes correlate with the level of consciousness in the patients with DOC. CONCLUSION: The degree of consciousness in patients with DOC was correlated with neural activity in the ACC induced by self-related stimuli. Our results not only shed light on the pathophysiology of DOC, but may also suggest a useful neural, and thus diagnostic, marker of the dysfunction of consciousness in vegetative patients. [less ▲]

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See detailNeuroimaging after coma.
Tshibanda, Luaba ULg; Vanhaudenhuyse, Audrey ULg; Boly, Mélanie ULg et al

in Neuroradiology (2010), 52(1), 15-24

Following coma, some patients will recover wakefulness without signs of consciousness (only showing reflex movements, i.e., the vegetative state) or may show non-reflex movements but remain without ... [more ▼]

Following coma, some patients will recover wakefulness without signs of consciousness (only showing reflex movements, i.e., the vegetative state) or may show non-reflex movements but remain without functional communication (i.e., the minimally conscious state). Currently, there remains a high rate of misdiagnosis of the vegetative state (Schnakers et. al. BMC Neurol, 9:35, 8) and the clinical and electrophysiological markers of outcome from the vegetative and minimally conscious states remain unsatisfactory. This should incite clinicians to use multimodal assessment to detect objective signs of consciousness and validate para-clinical prognostic markers in these challenging patients. This review will focus on advanced magnetic resonance imaging (MRI) techniques such as magnetic resonance spectroscopy, diffusion tensor imaging, and functional MRI (fMRI studies in both "activation" and "resting state" conditions) that were recently introduced in the assessment of patients with chronic disorders of consciousness. [less ▲]

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See detailVisual fixation in the vegetative state: an observational case series PET study.
Bruno, Marie-Aurélie ULg; Vanhaudenhuyse, Audrey ULg; Schnakers, Caroline ULg et al

in BMC Neurology (2010), 10

BACKGROUND: 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 ... [more ▼]

BACKGROUND: 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 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Our findings suggest that sustained visual fixation in (non-traumatic) disorders of consciousness does not necessarily reflect consciousness and higher order cortical brain function. [less ▲]

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See detailFunctional Neuroimaging Approaches to the Changing Borders of Consciousness
Noirhomme, Quentin ULg; Soddu, Andrea ULg; Vanhaudenhuyse, Audrey ULg et al

in Journal of Psychophysiology (2010), 24(2), 68-75

The bedside diagnosis of vegetative and minimally conscious patients is extremely challenging, and prediction of individual long-term outcome remains difficult. State-of the art neuroimaging methods could ... [more ▼]

The bedside diagnosis of vegetative and minimally conscious patients is extremely challenging, and prediction of individual long-term outcome remains difficult. State-of the art neuroimaging methods could help disentangle complex cases and offer new prognostic criteria. These methods can be divided into to three categories: First, new anatomical MRI neuroimaging methods, like diffusion tensor imaging (DTI) or spectroscopy, and passive functional imaging methods (looking at the brain’s activation induced by external stimuli), could provide new diagnostic and prognostic markers. Second, neuroimaging methods based on active collaboration from the patient could help to detect clinically unnoticed signs of consciousness. Third, developments in brain-computer interfaces based on EEG, functional MRI, or EMG offer communication possibilities in brain-damaged patients who can neither verbally nor nonverbally express their thoughts or wishes. These new approaches raise important issues not only from a clinical and ethical perspective (i.e., patients’ diagnosis, prognosis and management) but also from a neuroscientific standpoint, as they enrich our current understanding of the emergence and function of the conscious human mind. [less ▲]

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See detailCentral neuromodulation in cluster headache patients treated with occipital nerve stimulators: A PET study
Magis, Delphine ULg; Bruno, Marie-Aurélie ULg; Fumal, Arnaud ULg et al

in Acta Neurologica Belgica (2010), 110(Suppl 1), 17

OBJECTIVES: Use functional brain imaging to explore activity changes in centres involved in trigeminal pain processing and control before and after occipital neurostimulation in drug-resistant chronic ... [more ▼]

OBJECTIVES: Use functional brain imaging to explore activity changes in centres involved in trigeminal pain processing and control before and after occipital neurostimulation in drug-resistant chronic cluster headache patients. BACKGROUND: Occipital nerve stimulation (ONS) provides relief to about 60% of patients suffering from drug-resistant chronic cluster headache (drCCH). Its mode of action, however, remains elusive, but the long latency to meaningful effect suggests that ONS induces slow neuromodulation. METHODS: Ten drCCH patients underwent an 18FDG-PET scan after ONS durations varying between 0 and 30 months. All were scanned with ongoing ONS (ON) and with the stimulator switched OFF. RESULTS: After 6-30 months of ONS, 3 patients were pain free and 4 had a ≥ 90% reduction of attack frequency (responders). In patients overall compared to controls, several areas of the pain matrix were hypermetabolic: ipsilateral hypothalamus, midbrain and ipsilateral lower pons. All normalized after ONS, except the hypothalamus. Switching ON or OFF the stimulator had little influence on brain glucose metabolism. The perigenual anterior cingulate cortex (PACC) was hyperactive in ONS responders compared to non-responders. INTERPRETATION AND CONCLUSIONS: Metabolic normalization in the pain neuromatrix and lack of short-term changes induced by the stimulation support the hypothesis that ONS acts in drCCH through slow neuromodulatory processes. Selective activation in responders of PACC, a pivotal structure in the endogenous opioid system, suggests that ONS may restore balance within dysfunctioning pain control centres. That ONS is nothing but a symptomatic treatment might be illustrated by the persistent hypothalamic hypermetabolism which could explain why autonomic attacks may persist despite pain relief and why cluster attacks recur shortly after stimulator arrest. [less ▲]

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See detailQuelles attitudes médicales et éthiques adopter envers le patient en locked-in syndrome?
Thonnard, Marie ULg; Chatelle, Camille ULg; Gosseries, Olivia ULg et al

in Puybasset, Louis (Ed.) Enjeux éthiques en réanimation (2010)

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See detailThe nociception coma scale: A new tool to assess nociception in disorders of consciousness.
Schnakers, Caroline ULg; Chatelle, Camille ULg; Vanhaudenhuyse, Audrey ULg et al

in Pain (2010), 148

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 ... [more ▼]

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. [less ▲]

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See detailSleep vs Coma
Noirhomme, Quentin ULg; Laureys, Steven ULg; Boly, Mélanie ULg

in Frontiers in Neuroscience (2009), 3(3), 406-407

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See detailLife can be worth living in locked-in syndrome
Lule, Dorothee; Zickler, K.; Hacker, S. et al

in Progress in Brain Research (2009), 177

The locked-in syndrome (LIS) describes patients who are awake and conscious but severely deefferented leaving the patient in a state of almost complete immobility and loss of verbal communication. The ... [more ▼]

The locked-in syndrome (LIS) describes patients who are awake and conscious but severely deefferented leaving the patient in a state of almost complete immobility and loss of verbal communication. The etiology ranges from acute (e.g., brainstem stroke, which is the most frequent cause of LIS) to chronic causes (e.g., amyotrophic lateral sclerosis; ALS). In this article we review and present new data on the psychosocial adjustment to LIS. We refer to quality of life (QoL) and the degree of depressive symptoms as a measure of psychosocial adjustment. Various studies suggest that despite their extreme motor impairment, a significant number of LIS patients maintain a good QoL that seems unrelated to their state of physical functioning. Likewise, depression is not predicted by the physical state of the patients. A successful psychological adjustment to the disease was shown to be related to problem-oriented coping strategies, like seeking for information, and emotional coping strategies like denial--the latter may, nevertheless, vary with disease stage. Perceived social support seems to be the strongest predictor of psychosocial adjustment. QoL in LIS patients is often in the same range as in age-matched healthy individuals. Interestingly, there is evidence that significant others, like primary caregivers or spouses, rate LIS patients' QoL significantly lower than the patients themselves. With regard to depressed mood, ALS patients without symptoms focus significantly more often on internal factors that can be retained in the course of the disease contrary to patients with depressive symptoms who preferably name external factors as very important, such as health, which will degrade in the course of the disease. Typically, ALS patients with a higher degree of depressive symptoms experience significantly less "very pleasant" situations. The herein presented data strongly question the assumption among doctors, health-care workers, lay persons, and politicians that severe motor disability necessarily is intolerable and leads to end-of-life decisions or euthanasia. Existing evidence supports that biased clinicians provide less-aggressive medical treatment in LIS patients. Thus, psychological treatment for depression, effective strategies for coping with the disease, and support concerning the maintenance of the social network are needed to cope with the disease. Novel communication devices and assistive technology now offers an increasing number of LIS patients to resume a meaningful life and an active role in society. [less ▲]

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See detailI disturbi dello stato di coscienza come modello di studio dei suoi correlati neurali
Stanziano, Mario; Soddu, Andrea ULg; Papa, Michele et al

in Paradoxa (2009), 3(4), 106-118

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See detailSleep in the vegetative and minimally conscious states
Cologan, Victor ULg; Schabus, Manuel; Maquet, Pierre ULg et al

Poster (2009, June)

Résultats préliminaires de l'étude du sommeil chez les patients cérébrolésés en état de conscience altéré.

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