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See detailNear-Death Experiences in patients with locked-in syndrome: Not always a blissful journey
Charland-Verville, Vanessa ULiege; Lugo, Zulay; Jourdan, Jean-Pierre et al

in Consciousness & Cognition (2015), 34

Memories of Near-Death Experiences (NDEs) most often are recounted as emotionally positive events. At present, no satisfactory explanatory model exists to fully account for the rich phenomenology of NDEs ... [more ▼]

Memories of Near-Death Experiences (NDEs) most often are recounted as emotionally positive events. At present, no satisfactory explanatory model exists to fully account for the rich phenomenology of NDEs following a severe acute brain injury. The particular population of patients with locked-in syndrome (LIS) provides a unique opportunity to study NDEs following infratentorial brain lesions. We here retrospectively characterized the content of NDEs in 8 patients with LIS caused by an acute brainstem lesion (i.e., ‘‘LIS NDEs’’) and 23 NDE experiencers after coma with supratentorial lesions (i.e., ‘‘classical NDEs’’). Compared to ‘‘classical NDEs’’, ‘‘LIS NDEs’’ less frequently experienced a feeling of peacefulness or well-being. It could be hypothesized that NDEs containing less positive emotions might have a specific neuroanatomical substrate related to impaired pontine/paralimbic connectivity or alternatively might be related to the emotional distress caused by the presence of conscious awareness in a paralyzed body. [less ▲]

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See detailCortical responses to transcranial magnetic stimulation during Non-Rapid Eye Movement Sleep
Gosseries, Olivia ULiege; Jaakko, Nieminen; Siclari, Francesca et al

Poster (2015, March)

Transcranial magnetic stimulation coupled to high-density electroencephalography (TMS-EEG) allows for directly and non-invasively stimulating the brain and recording the subsequent cortical response ... [more ▼]

Transcranial magnetic stimulation coupled to high-density electroencephalography (TMS-EEG) allows for directly and non-invasively stimulating the brain and recording the subsequent cortical response. Previous TMS-EEG studies have shown clear-cut differences between conscious and unconscious conditions. When subjects are unconscious, as in non-rapid eye movement (NREM) sleep early in the night (stage N3), anesthesia or coma, TMS typically triggers a stereotypical and local slow-wave response. When they are conscious, as in normal wakefulness and rapid eye movement sleep (REM) sleep, brain responses to TMS are long-lasting, widespread, complex, and differentiated. In this study, we performed TMS-EEG during NREM sleep in stage 2 (N2) and N3 on 7 healthy participants. Brain activity was recorded using a 60-channel TMS-compatible EEG and single-pulse TMS was applied (up to 285 pulses per session) on the superior parietal cortex. After each TMS session (5 to 15 sessions per night), subjects were awakened to ask for a dream report. TMS-EEG responses were analyzed using the global mean field amplitude (GMFA), the perturbational complexity index (PCI), as well as time-frequency measures. Our results show that the TMS-EEG response during N3 is larger and slower than during N2 sleep. The GMFA is higher and PCI is lower in N3 as compared to N2 sleep. Moreover, N3 recordings showed activation at lower frequency bands after TMS as compared to N2 sleep. Additionally, TMS-EEG responses vary depending on whether subjects do or do not report a dream. TMS-EEG might provide valuable information for characterizing neurophysiological fluctuations and levels of consciousness within NREM sleep. [less ▲]

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See detailCerebral responses and role of the prefrontal cortex in conditioned pain modulation: an fMRI study in healthy subjects
Bogdanov, Volodymyr; Vigano, Alessandro; Noirhomme, Quentin ULiege et al

in Behavioural Brain Research (2015)

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See detailIntrinsic fMRI functional architecture differentiates single patients after severe brain injury
Demertzi, Athina ULiege; Antonopoulos, Georgios ULiege; Heine, Lizette ULiege et al

Poster (2015)

Background: Resting state acquisitions are by definition appropriate to assess non-communicating subjects. We here assessed the clinical relevance of systems-level resting state fMRI in patients with ... [more ▼]

Background: Resting state acquisitions are by definition appropriate to assess non-communicating subjects. We here assessed the clinical relevance of systems-level resting state fMRI in patients with disorders of consciousness with the aim to promote single-patient diagnostics. Methods: Seventy three patients in minimally conscious state (MCS), vegetative state/unresponsive wakefulness syndrome (VS/UWS) and coma were scanned in 3 different centers. The main analysis was performed on the dataset coming from one centre (Liège, 51 patients; 26 MCS, 19 VS/UWS, 6 coma; 16 traumatic, 32 non-traumatic, 3 mixed; 35 patients assessed >1 month post-insult) for whom the clinical diagnosis with the Coma Recovery Scale-Revised (CRS-R) was congruent with positron emission tomography scanning. Using a multiple-seed correlation approach, group-level functional connectivity was investigated for the default mode, frontoparietal, salience, auditory, sensorimotor and visual networks. Between-group inferential statistics and machine learning were used to identify each network’s capacity to discriminate between patients in MCS and VS/UWS. Data from 22 patients independently scanned in two other centres (Salzburg: 10 MCS, 5 VS/UWS; New York: 5 MCS, 1 VS/UWS, 1 emerged from MCS) were used to validate the classification with the indetified features. Results: CRS-R total scores correlated with key regions of each network reflecting their involvement in consciousness-related processes. Although all networks had a high discriminative capacity (>80%) for separating patients in MCS and VS/UWS, the auditory network was ranked the most highly. Specifically, bilateral auditory and visual cortices of the auditory network were more functionally connected in patients in MCS compared to VS/UWS. Connectivity values in these three regions discriminated congruently 20 out of 22 independently assessed patients. Conclusions: These findings highlight the significance of preserved multisensory integration and top-down processing in minimal consciousness which are seemingly supported by auditory-visual crossmodal connectivity, and promote the clinical utility of the resting paradigm for single-patient diagnostics. [less ▲]

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See detailThalamic volume as a biomarker for Disorders Of Consciousness. Progress in Biomedical Optics and Imaging
Rubeaux, M; Mahalingam, J; Gomez, F et al

in Proceedings of SPIE (2015)

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See detailPreserved Covert Cognition in Noncommunicative Patients With Severe Brain Injury?
schnakers, caroline; Giacino, Joseph T; Løvstad, Marianne et al

in Neurorehabilitation and Neural Repair (2015)

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See detailHypnosis modulates behavioural measures and subjective ratings about external and internal awareness
Demertzi, Athina ULiege; VANHAUDENHUYSE, Audrey ULiege; Noirhomme, Quentin ULiege et al

in Journal of Physiology - Paris (2015), 109(4), 173-179

In altered subjective states, the behavioural quantification of external and internal awareness remains challenging due to the need for reports on the subjects’ behalf. With the aim to characterize the ... [more ▼]

In altered subjective states, the behavioural quantification of external and internal awareness remains challenging due to the need for reports on the subjects’ behalf. With the aim to characterize the behavioural counterpart of external and internal awareness in a modified subjective condition, we used hypnosis during which subjects remain fully responsive. Eleven right-handed subjects reached a satisfactory level of hypnotisability as evidenced by subjective reports on arousal, absorption and dissociation. Compared to normal wakefulness, in hypnosis (a) participants’ self-ratings for internal awareness increased and self-ratings for external awareness decreased, (b) the two awareness components tended to anticorrelate less and the switches between external and internal awareness self-ratings were less frequent, and (c) participants’ reaction times were higher and lapses in key presses were more frequent. The identified imbalance between the two components of awareness is considered as of functional relevance to subjective (meta)cognition, possibly mediated by allocated attentional properties brought about by hypnosis. Our results highlight the presence of a cognitive counterpart in resting state, indicate that the modified contents of awareness are measurable behaviourally, and provide leverage for investigations of more challenging altered conscious states, such as anaesthesia, sleep and disorders of consciousness. [less ▲]

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See detailBeyond the gaze: Communicating in chronic locked-in syndrome
Lugo, Z.R; Bruno, Marie-Aurelie; Gosseries, Olivia ULiege et al

in Brain Injury (2015), 29

OBJECTIVE Locked-in syndrome (LIS) usually follows a brainstem stroke and is characterized by paralysis of all voluntary muscles (except eyes' movements or blinking) and lack of speech with preserved ... [more ▼]

OBJECTIVE Locked-in syndrome (LIS) usually follows a brainstem stroke and is characterized by paralysis of all voluntary muscles (except eyes' movements or blinking) and lack of speech with preserved consciousness. Several tools have been developed to promote communication with these patients. The aim of the study was to evaluate the current status regarding communication in a cohort of LIS patients. DESIGN A survey was conducted in collaboration with the French Association of Locked-in syndrome (ALIS). SUBJECTS AND METHODS Two hundred and four patients, members of ALIS, were invited to fill in a questionnaire on communication issues and clinical evolution (recovery of verbal language and movements, presence of visual and/or auditory deficits). RESULTS Eighty-eight responses were processed. All respondents (35% female, mean age = 52 ± 12 years, mean time in LIS = 10 ± 6 years) reported using a yes/no communication code using mainly eyes' movements and 62% used assisting technology; 49% could communicate through verbal language and 73% have recovered some functional movements within the years. CONCLUSION The results highlight the possibility to recover non-eye dependent communication, speech production and some functional movement in the majority of chronic LIS patients. [less ▲]

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See detailConsciousness: And Disorders of Consciousness
Heine, Lizette ULiege; Demertzi, Athina ULiege; Laureys, Steven ULiege et al

in Toga, Arthur W (Ed.) Brain mapping : an encyclopedic reference (2015)

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See detailDetecting Levels of Consciousness
Demertzi, Athina ULiege; Laureys, Steven ULiege

in Levy, N; Clausen, J (Eds.) Handbook of Neuroethics (2015)

Patients with disordered consciousness due to brain injury pose medical and ethical challenges. Rates of clinical misdiagnosis of “vegetative”/unresponsive, minimally conscious and locked-in syndrome ... [more ▼]

Patients with disordered consciousness due to brain injury pose medical and ethical challenges. Rates of clinical misdiagnosis of “vegetative”/unresponsive, minimally conscious and locked-in syndrome states remain challengingly high. Clinical misdiagnosis raises profound ethical concerns in terms of medical management, treatment of pain, and end-of-life decisions. Therefore, valid diagnosis is of utmost importance in clinical settings. A number of neuroimaging and electrophysiology studies now suggest that some behaviorally “vegetative state” patients may nevertheless show atypical cortical activation during resting state conditions; in some cases, they are able to follow commands or even communicate through willfully modified brain activity. Advances in investigating disorders of consciousness with neuroimaging techniques promise to lead to a more accurate understanding of individual patients’ cognitive abilities and to shed light on the gray zones of these clinical conditions. The formulation of an ethical framework which will strike a balance between the protection of these patients and further research on disorders of consciousness is an ethical, clinical, and scientific demand. [less ▲]

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See detailImaging correlation in non-communicating patients
Heine, Lizette ULiege; Di Perri, Carol ULiege; Soddu, Andrea ULiege et al

in Rossetti, A.O; Laureys, Steven (Eds.) Clinical Neurophysiology in Disorders of Consciousness-Brain Function Monitoring in the ICU and beyond (2015)

The diagnosis and medical management of patients with acute or chronic disorders of consciousness (DOC) are challenging. Motor-independent functional neuroimaging technologies are increasingly employed to ... [more ▼]

The diagnosis and medical management of patients with acute or chronic disorders of consciousness (DOC) are challenging. Motor-independent functional neuroimaging technologies are increasingly employed to study covert cognitive processes in the absence of behavioural reports. Studies with functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) performed in this patient population have utilized active, passive and restingstate paradigms. Active paradigms refer to mental imagery tasks that measure wilful modulation of brain signal in specific brain areas, aiming to detect command-following. Passive paradigms are used to measure brain responses to external sensory stimulation (e.g. auditory, somatosensory and visual). Alternatively, in resting-state paradigms, spontaneous brain function is assessed while subjects receive no external stimulation and are instructed to let their mind wander. Independently from each other, these methods have shown differences between healthy controls and patients, as well as among patients with DOC. However, these techniques cannot yet be used in clinical settings before robust information at the single-subject level will be provided: it is expected that multimodal research will improve the single-patient diagnosis, shed light on the prognostic biomarkers, and eventually promote the medical management of patients with consciousness alterations. [less ▲]

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See detailThinking on patients’ behalf: attitudes of healthcare providers towards medico-ethical issues in non-communicating patients
Demertzi, Athina ULiege; Laureys, Steven ULiege

in Sturma, D; Honnefelder, L; Fuchs, M (Eds.) Yearbook for Science and Ethics (2015)

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See detailConsciousness and complexity during unresponsiveness induced by propofol, xenon, and ketamine
Sarasso, S.; Boly, M.; Napolitani, M. et al

in Current Biology (2015), 25(23), 3099-3105

A common endpoint of general anesthetics is behavioral unresponsiveness [1], which is commonly associated with loss of consciousness. However, subjects can become disconnected from the environment while ... [more ▼]

A common endpoint of general anesthetics is behavioral unresponsiveness [1], which is commonly associated with loss of consciousness. However, subjects can become disconnected from the environment while still having conscious experiences, as demonstrated by sleep states associated with dreaming [2]. Among anesthetics, ketamine is remarkable [3] in that it induces profound unresponsiveness, but subjects often report ketamine dreams upon emergence from anesthesia [4-9]. Here, we aimed at assessing consciousness during anesthesia with propofol, xenon, and ketamine, independent of behavioral responsiveness. To do so, in 18 healthy volunteers, we measured the complexity of the cortical response to transcranial magnetic stimulation (TMS) - an approach that has proven helpful in assessing objectively the level of consciousness irrespective of sensory processing and motor responses [10]. In addition, upon emergence from anesthesia, we collected reports about conscious experiences during unresponsiveness. Both frontal and parietal TMS elicited a low-amplitude electroencephalographic (EEG) slow wave corresponding to a local pattern of cortical activation with low complexity during propofol anesthesia, a high-amplitude EEG slow wave corresponding to a global, stereotypical pattern of cortical activation with low complexity during xenon anesthesia, and a wakefulness-like, complex spatiotemporal activation pattern during ketamine anesthesia. Crucially, participants reported no conscious experience after emergence from propofol and xenon anesthesia, whereas after ketamine they reported long, vivid dreams unrelated to the external environment. These results are relevant because they suggest that brain complexity may be sensitive to the presence of disconnected consciousness in subjects who are considered unconscious based on behavioral responses. © 2015 Elsevier Ltd All rights reserved. [less ▲]

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See detailBehavioural Diagnosis of Disorders of Consciousness
Thibaut, Aurore ULiege; Di Perri, Carol ULiege; Bodart, Olivier ULiege et al

in Rossetti, Andrea; Laureys, Steven (Eds.) Clinical Neurophysiology in Disorders of Consciousness (2015)

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See detailChronic disorders of consciousness
Thibaut, Aurore ULiege; BODART, Olivier ULiege; Laureys, Steven ULiege et al

in Canavero, Sergio (Ed.) Surgical Principles of Therapeutic Cortical Stimulation (2015)

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See detailClinical Response to tDCS Depends on Residual Brain Metabolism and Grey Matter Integrity in Patients With Minimally Conscious State.
Thibaut, Aurore ULiege; Di Perri, Carol; Chatelle, Camille ULiege et al

in Brain stimulation (2015), 8(6), 1116-23

BACKGROUND: Transcranial direct current stimulation (tDCS) was recently shown to promote recovery of voluntary signs of consciousness in some patients in minimally conscious state (MCS). However, it ... [more ▼]

BACKGROUND: Transcranial direct current stimulation (tDCS) was recently shown to promote recovery of voluntary signs of consciousness in some patients in minimally conscious state (MCS). However, it remains unclear why clinical improvement is only observed in a subgroup of patients. OBJECTIVES: In this retrospective study, we investigated the relationship between tDCS responsiveness and neuroimaging data from MCS patients. METHODS: Structural Magnetic Resonance Imaging (MRI), Fluorodeoxyglucose Positron emission tomography (FDG-PET) and clinical electroencephalography (EEG) were acquired in 21 sub-acute and chronic MCS patients (8 tDCS responders) who subsequently (<48 h) received left dorsolateral prefrontal (DLPF) tDCS in a double-blind randomized cross-over trial. The behavioral data have been published elsewhere (Thibaut et al., Neurology, 2014). RESULTS: Grey matter atrophy was observed in non-responders as compared with responders in the left DLPF cortex, the medial-prefrontal cortex, the cingulate cortex, the hippocampi, part of the rolandic regions, and the left thalamus. FDG-PET showed hypometabolism in non-responders as compared with responders in the left DLPF cortex, the medial-prefrontal cortex, the precuneus, and the thalamus. EEG did not show any difference between the two groups. CONCLUSION: Our findings suggest that the transient increase of signs of consciousness following left DLPF tDCS in patients in MCS require grey matter preservation and residual metabolic activity in cortical and subcortical brain areas known to be involved in attention and working memory. These results further underline the critical role of long-range cortico-thalamic connections in consciousness recovery, providing important information for guidelines on the use of tDCS in disorders of consciousness. [less ▲]

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See detailAn empirical classification scheme for detection of impossible and improbable CRS-R subscore combinations
Chatelle, Camille ULiege; Bodien, Yelena Guller; Carlowicz, Cecilia et al

Poster (2015)

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See detailInterfaces cerveau-ordinateur, locked-in syndrome et troubles de la conscience.
Lesenfants, Damien; Chatelle, Camille ULiege; Laureys, Steven ULiege et al

in Medecine sciences : M/S (2015), 31(10), 904-11

Detecting signs of consciousness in patients with severe brain injury constitutes a real challenge for clinicians. The current gold standard in clinical diagnosis is the behavioral scale relying on motor ... [more ▼]

Detecting signs of consciousness in patients with severe brain injury constitutes a real challenge for clinicians. The current gold standard in clinical diagnosis is the behavioral scale relying on motor abilities, which are often impaired or nonexistent in these patients. In this context, brain-computer interfaces (BCIs) could offer a potential complementary tool to detect signs of consciousness whilst bypassing the usual motor pathway. In addition to complementing behavioral assessments and potentially reducing error rate, BCIs could also serve as a communication tool for paralyzed but conscious patients, e.g., suffering from Locked-In Syndrome. In this paper, we report on recent work conducted by the Coma Science Group on BCI technology, aiming to optimize diagnosis and communication in patients with disorders of consciousness and Locked-In syndrome. [less ▲]

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See detailBrain computer interface for assessing consciousness in severely brain-injured patients
Chatelle, Camille ULiege; Lesenfants, Damien; Bodien, Yelena G et al

in Rosetti, Andrea; LAUREYS, Steven (Eds.) Clinical Neurophysiology in Disorders of Consciousness (2015)

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See detailQuantitative rates of brain glucose metabolism distinguish minimally conscious from vegetative state patients.
Stender, Johan; Kupers, Ron; Rodell, Anders et al

in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (2015), 35(1), 58-65

The differentiation of the vegetative or unresponsive wakefulness syndrome (VS/UWS) from the minimally conscious state (MCS) is an important clinical issue. The cerebral metabolic rate of glucose (CMRglc ... [more ▼]

The differentiation of the vegetative or unresponsive wakefulness syndrome (VS/UWS) from the minimally conscious state (MCS) is an important clinical issue. The cerebral metabolic rate of glucose (CMRglc) declines when consciousness is lost, and may reveal the residual cognitive function of these patients. However, no quantitative comparisons of cerebral glucose metabolism in VS/UWS and MCS have yet been reported. We calculated the regional and whole-brain CMRglc of 41 patients in the states of VS/UWS (n=14), MCS (n=21) or emergence from MCS (EMCS, n=6), and healthy volunteers (n=29). Global cortical CMRglc in VS/UWS and MCS averaged 42% and 55% of normal, respectively. Differences between VS/UWS and MCS were most pronounced in the frontoparietal cortex, at 42% and 60% of normal. In brainstem and thalamus, metabolism declined equally in the two conditions. In EMCS, metabolic rates were indistinguishable from those of MCS. Ordinal logistic regression predicted that patients are likely to emerge into MCS at CMRglc above 45% of normal. Receiver-operating characteristics showed that patients in MCS and VS/UWS can be differentiated with 82% accuracy, based on cortical metabolism. Together these results reveal a significant correlation between whole-brain energy metabolism and level of consciousness, suggesting that quantitative values of CMRglc reveal consciousness in severely brain-injured patients. [less ▲]

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