Assessment and detection of pain in noncommunicative severely brain-injured patients.
Schnakers, Caroline ; Chatelle, Camille ; Majerus, Steve 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 ▲]Detailed reference viewed: 22 (3 ULg)
État végétatif et état de conscience minimale : un devenir pire que la mort ?
Bruno, Marie-Aurélie ; Gosseries, Olivia ; Vanhaudenhuyse, Audrey et al
Part of book (2010)Detailed reference viewed: 28 (6 ULg)
Breakdown of within- and between-network resting state functional magnetic resonance imaging connectivity during propofol-induced loss of consciousness.
Boveroux, Pierre ; Vanhaudenhuyse, Audrey ; Bruno, Marie-Aurélie 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 ▲]Detailed reference viewed: 74 (11 ULg)
Anterior cingulate activity and the self in disorders of consciousness.
; ; 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 ▲]Detailed reference viewed: 31 (4 ULg)
Neuroimaging after coma.
Tshibanda, Luaba ; Vanhaudenhuyse, Audrey ; Boly, Mélanie 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 ▲]Detailed reference viewed: 41 (6 ULg)
Visual fixation in the vegetative state: an observational case series PET study.
Bruno, Marie-Aurélie ; Vanhaudenhuyse, Audrey ; Schnakers, Caroline 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 ▲]Detailed reference viewed: 27 (4 ULg)
Functional Neuroimaging Approaches to the Changing Borders of Consciousness
Noirhomme, Quentin ; Soddu, Andrea ; Vanhaudenhuyse, Audrey 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 ▲]Detailed reference viewed: 27 (8 ULg)
Central neuromodulation in cluster headache patients treated with occipital nerve stimulators: A PET study
Magis, Delphine ; Bruno, Marie-Aurélie ; Fumal, Arnaud 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 ▲]Detailed reference viewed: 36 (4 ULg)
Quelles attitudes médicales et éthiques adopter envers le patient en locked-in syndrome?
Thonnard, Marie ; Chatelle, Camille ; Gosseries, Olivia et al
in Puybasset, Louis (Ed.) Enjeux éthiques en réanimation (2010)Detailed reference viewed: 32 (7 ULg)
The nociception coma scale: A new tool to assess nociception in disorders of consciousness.
Schnakers, Caroline ; Chatelle, Camille ; Vanhaudenhuyse, Audrey 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 ▲]Detailed reference viewed: 78 (9 ULg)
Life can be worth living in locked-in syndrome
; ; 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 ▲]Detailed reference viewed: 55 (2 ULg)
I disturbi dello stato di coscienza come modello di studio dei suoi correlati neurali
; Soddu, Andrea ; et al
in Paradoxa (2009), 3(4), 106-118Detailed reference viewed: 53 (0 ULg)
Sleep in the vegetative and minimally conscious states
Cologan, Victor ; ; Maquet, Pierre et al
Poster (2009, June)
Résultats préliminaires de l'étude du sommeil chez les patients cérébrolésés en état de conscience altéré.Detailed reference viewed: 7 (0 ULg)
Organ Procurement After Euthanasia: Belgian Experience
; ; et al
in Transplantation Proceedings (2009), 41
Euthanasia was legalized in Belgium in 2002 for adults under strict conditions. The patient must be in a medically futile condition and of constant and unbearable physical or mental suffering that cannot ... [more ▼]
Euthanasia was legalized in Belgium in 2002 for adults under strict conditions. The patient must be in a medically futile condition and of constant and unbearable physical or mental suffering that cannot be alleviated, resulting from a serious and incurable disorder caused by illness or accident. Between 2005 and 2007, 4 patients (3 in Antwerp and 1 in Liège) expressed their will for organ donation after their request for euthanasia was granted. Patients were aged 43 to 50 years and had a debilitating neurologic disease, either after severe cerebrovascular accident or primary progressive multiple sclerosis. Ethical boards requested complete written scenario with informed consent of donor and relatives, clear separation between euthanasia and organ procurement procedure, and all procedures to be performed by senior staff members and nursing staff on a voluntary basis. The euthanasia procedure was performed by three independent physicians in the operating room. After clinical diagnosis of cardiac death, organ procurement was performed by femoral vessel cannulation or quick laparotomy. In 2 patients, the liver, both kidneys, and pancreatic islets (one case) were procured and transplanted; in the other 2 patients, there was additional lung procurement and transplantation. Transplant centers were informed of the nature of the case and the elements of organ procurement. There was primary function of all organs. The involved physicians and transplant teams had the well-discussed opinion that this strong request for organ donation after euthanasia could not be waived. A clear separation between the euthanasia request, the euthanasia procedure, and the organ procurement procedure is necessary. [less ▲]Detailed reference viewed: 163 (29 ULg)
Neurophysiological correlates of hypnotic analgesia
Vanhaudenhuyse, Audrey ; Boly, Mélanie ; Laureys, Steven et al
in Contemporary Hypnosis (2009), 26(1), 15-23
This short review describes recent advances in understanding hypnotic modulation of pain. Our current understanding of pain perception is followed by a critical review of the hypnotic analgesia studies ... [more ▼]
This short review describes recent advances in understanding hypnotic modulation of pain. Our current understanding of pain perception is followed by a critical review of the hypnotic analgesia studies using EEG, evoked potential and functional imaging methodologies. [less ▲]Detailed reference viewed: 20 (3 ULg)
Reaching across the abyss: recent advances in functional magnetic resonance imaging and their potential relevance to disorders of consciousness
Soddu, Andrea ; Boly, Mélanie ; et al
in Progress in Brain Research (2009), 177
Disorders of consciousness (DOC) raise profound scientific, clinical, ethical, and philosophical issues. Growing knowledge on fundamental principles of brain organization in healthy individuals offers new ... [more ▼]
Disorders of consciousness (DOC) raise profound scientific, clinical, ethical, and philosophical issues. Growing knowledge on fundamental principles of brain organization in healthy individuals offers new opportunities for a better understanding of residual brain function in DOCs. We here discuss new perspectives derived from a recently proposed scheme of brain organization underlying consciousness in healthy individuals. In this scheme, thalamo-cortical networks can be divided into two, often antagonistic, global systems: (i) a system of externally oriented, sensory-motor networks (the "extrinsic" system); and (ii) a system of inward-oriented networks (the "intrinsic" or default system). According to this framework, four distinct mental states would be possible that could be relevant for understanding DOCs. In normal healthy volunteers and locked-in syndrome patients, a state of high functionality of both the extrinsic and intrinsic or default systems is expected--associated with full awareness of environment and self. In this case, mental imagery tasks combined with fMRI can be used to detect covert awareness in patients that are unable to communicate. <br /> <br />According to the framework, two complementary states of system imbalance are also possible, in which one system is in a hyperfunctional state, while the other is hypoactive. Extrinsic system hyperfunction is expected to lead to a state of total sensory-motor "absorption" or "lost self." In contrast, intrinsic or default system hyperfunction is expected to lead to a state of complete detachment from the external world. A state where both extrinsic and intrinsic systems are hypofunctional is predicted to lead to markedly impaired consciousness as seen in DOCs. Finally, we review the potential use of ultra-slow fluctuations in BOLD signal as a tool for assessing the functional integrity of extrinsic and intrinsic systems during "resting state" fMRI acquisitions. In particular, we discuss the potential provided by assessment of these slow spontaneous BOLD fluctuations as a novel tool in assessing the cognitive state and chances of recovery from brain pathologies underlying DOCs. [less ▲]Detailed reference viewed: 48 (6 ULg)
Dualism persists in the science of mind.
Demertzi, Athina ; ; Ledoux, Didier et al
in Annals of the New York Academy of Sciences (2009), 1157
The relationship between mind and brain has philosophical, scientific, and practical implications. Two separate but related surveys from the University of Edinburgh (University students, n= 250) and the ... [more ▼]
The relationship between mind and brain has philosophical, scientific, and practical implications. Two separate but related surveys from the University of Edinburgh (University students, n= 250) and the University of Liege (health-care workers, lay public, n= 1858) were performed to probe attitudes toward the mind-brain relationship and the variables that account for differences in views. Four statements were included, each relating to an aspect of the mind-brain relationship. The Edinburgh survey revealed a predominance of dualistic attitudes emphasizing the separateness of mind and brain. In the Liege survey, younger participants, women, and those with religious beliefs were more likely to agree that the mind and brain are separate, that some spiritual part of us survives death, that each of us has a soul that is separate from the body, and to deny the physicality of mind. Religious belief was found to be the best predictor for dualistic attitudes. Although the majority of health-care workers denied the distinction between consciousness and the soma, more than one-third of medical and paramedical professionals regarded mind and brain as separate entities. The findings of the study are in line with previous studies in developmental psychology and with surveys of scientists' attitudes toward the relationship between mind and brain. We suggest that the results are relevant to clinical practice, to the formulation of scientific questions about the nature of consciousness, and to the reception of scientific theories of consciousness by the general public. [less ▲]Detailed reference viewed: 65 (5 ULg)
Another kind of 'BOLD Response': answering multiple-choice questions via online decoded single-trial brain signals.
; ; et al
in Progress in Brain Research (2009), 177
The term 'locked-in'syndrome (LIS) describes a medical condition in which persons concerned are severely paralyzed and at the same time fully conscious and awake. The resulting anarthria makes it ... [more ▼]
The term 'locked-in'syndrome (LIS) describes a medical condition in which persons concerned are severely paralyzed and at the same time fully conscious and awake. The resulting anarthria makes it impossible for these patients to naturally communicate, which results in diagnostic as well as serious practical and ethical problems. Therefore, developing alternative, muscle-independent communication means is of prime importance. Such communication means can be realized via brain-computer interfaces (BCIs) circumventing the muscular system by using brain signals associated with preserved cognitive, sensory, and emotional brain functions. Primarily, BCIs based on electrophysiological measures have been developed and applied with remarkable success. Recently, also blood flow-based neuroimaging methods, such as functional magnetic resonance imaging (fMRI) and functional near-infrared spectroscopy (fNIRS), have been explored in this context. After reviewing recent literature on the development of especially hemodynamically based BCIs, we introduce a highly reliable and easy-to-apply communication procedure that enables untrained participants to motor-independently and relatively effortlessly answer multiple-choice questions based on intentionally generated single-trial fMRI signals that can be decoded online. Our technique takes advantage of the participants' capability to voluntarily influence certain spatio-temporal aspects of the blood oxygenation level-dependent (BOLD) signal: source location (by using different mental tasks), signal onset and offset. We show that healthy participants are capable of hemodynamically encoding at least four distinct information units on a single-trial level without extensive pretraining and with little effort. Moreover, real-time data analysis based on simple multi-filter correlations allows for automated answer decoding with a high accuracy (94.9%) demonstrating the robustness of the presented method. Following our 'proof of concept', the next step will involve clinical trials with LIS patients, undertaken in close collaboration with their relatives and caretakers in order to elaborate individually tailored communication protocols. As our procedure can be easily transferred to MRI-equipped clinical sites, it may constitute a simple and effective possibility for online detection of residual consciousness and for LIS patients to communicate basic thoughts and needs in case no other alternative communication means are available (yet)--especially in the acute phase of the LIS. Future research may focus on further increasing the efficiency and accuracy of fMRI-based BCIs by implementing sophisticated data analysis methods (e.g., multivariate and independent component analysis) and neurofeedback training techniques. Finally, the presented BCI approach could be transferred to portable fNIRS systems as only this would enable hemodynamically based communication in daily life situations. [less ▲]Detailed reference viewed: 63 (3 ULg)