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See detailThalamus, Brainstem and Salience Network Connectivity Changes During Propofol-Induced Sedation and Unconsciousness
Guldenmund, Justus Pieter ULg; Demertzi, Athina ULg; BOVEROUX, Pierre ULg et al

in Brain connectivity (2013), 3

In this functional magnetic resonance imaging study, we examined the effect of mild propofol sedation and propofol-induced unconsciousness on resting state brain connectivity, using graph analysis based ... [more ▼]

In this functional magnetic resonance imaging study, we examined the effect of mild propofol sedation and propofol-induced unconsciousness on resting state brain connectivity, using graph analysis based on independent component analysis and a classical seed-based analysis. Contrary to previous propofol research, which mainly emphasized the importance of connectivity in the default mode network (DMN) and external control network (ECN), we focused on the salience network, thalamus, and brainstem. The importance of these brain regions in brain arousal and organization merits a more detailed examination of their connectivity response to propofol. We found that the salience network disintegrated during propofol-induced unconsciousness. The thalamus decreased connectivity with the DMN, ECN, and salience network, while increasing connectivity with sensorimotor and auditory/insular cortices. Brainstem regions disconnected from the DMN with unconsciousness, while the pontine tegmental area increased connectivity with the insulae during mild sedation. These findings illustrate that loss of consciousness is associated with a wide variety of decreases and increases of both cortical and subcortical connectivity. It furthermore stresses the necessity of also examining resting state connectivity in networks representing arousal, not only those associated with awareness. [less ▲]

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See detailProbing command following in patients with disorders of consciousness using a brain-computer interface.
Lule, Dorothee; Noirhomme, Quentin ULg; Kleih, Sonja C. et al

in Clinical Neurophysiology (2013), 124(1), 101-6

OBJECTIVE: To determine if brain-computer interfaces (BCIs) could serve as supportive tools for detecting consciousness in patients with disorders of consciousness by detecting response to command and ... [more ▼]

OBJECTIVE: To determine if brain-computer interfaces (BCIs) could serve as supportive tools for detecting consciousness in patients with disorders of consciousness by detecting response to command and communication. METHODS: We tested a 4-choice auditory oddball EEG-BCI paradigm on 16 healthy subjects and 18 patients in a vegetative state/unresponsive wakefulness syndrome, in a minimally conscious state (MCS), and in locked-in syndrome (LIS). Subjects were exposed to 4 training trials and 10 -12 questions. RESULTS: Thirteen healthy subjects and one LIS patient were able to communicate using the BCI. Four of those did not present with a P3. One MCS patient showed command following with the BCI while no behavioral response could be detected at bedside. All other patients did not show any response to command and could not communicate with the BCI. CONCLUSION: The present study provides evidence that EEG based BCI can detect command following in patients with altered states of consciousness and functional communication in patients with locked-in syndrome. However, BCI approaches have to be simplified to increase sensitivity. SIGNIFICANCE: For some patients without any clinical sign of consciousness, a BCI might bear the potential to employ a "yes-no" spelling device offering the hope of functional interactive communication. [less ▲]

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See detailPain perception in disorders of consciousness: neuroscience, clinical care, and ethics in dialogue
Demertzi, Athina ULg; Racine, Eric; Bruno, Marie-Aurélie ULg et al

in Neuroethics (2013), 6(1), 37-50

Pain, suffering and positive emotions in patients in vegetative state/unresponsive wakefulness syndrome (VS/UWS) and minimally conscious states (MCS) pose clinical and ethical challenges. Clinically, we ... [more ▼]

Pain, suffering and positive emotions in patients in vegetative state/unresponsive wakefulness syndrome (VS/UWS) and minimally conscious states (MCS) pose clinical and ethical challenges. Clinically, we evaluate behavioural responses after painful stimulation and also emotionally-contingent behaviours (e.g., smiling). Using stimuli with emotional valence, neuroimaging and electrophysiology technologies can detect subclinical remnants of preserved capacities for pain which might influence decisions about treatment limitation. To date, no data exist as to how healthcare providers think about end-of-life options (e.g., withdrawal of artificial nutrition and hydration) in the presence or absence of pain in non-communicative patients. Here, we aimed to better clarify this issue by re-analyzing previously published data on pain perception (Prog Brain Res 2009 177, 329–38) and end-of-life decisions (J Neurol 2010 258, 1058–65) in patients with disorders of consciousness. In a sample of 2259 European healthcare professionals we found that, for VS/UWS more respondents agreed with treatment withdrawal when they considered that VS/UWS patients did not feel pain (77%) as compared to those who thought VS/UWS did feel pain (59%). This interaction was influenced by religiosity and professional background. For MCS, end-of-life attitudes were not influenced by opinions on pain perception. Within a contemporary ethical context we discuss (1) the evolving scientific understandings of pain perception and their relationship to existing clinical and ethical guidelines; (2) the discrepancies of attitudes within (and between) healthcare providers and their consequences for treatment approaches, and (3) the implicit but complex relationship between pain perception and attitudes toward life-sustaining treatments. [less ▲]

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See detailConsciousness supporting networks
Demertzi, Athina ULg; Soddu, Andrea ULg; Laureys, Steven ULg

in Current Opinion in Neurobiology (2013), 23(2), 239-244

Functional neuroimaging shows that patients with disorders of consciousness exhibit disrupted system-level functional connectivity. Unresponsive/"vegetative state" patients preserve wakefulness networks ... [more ▼]

Functional neuroimaging shows that patients with disorders of consciousness exhibit disrupted system-level functional connectivity. Unresponsive/"vegetative state" patients preserve wakefulness networks of brainstem and basal forebrain but the cerebral networks accounting for external perceptual awareness and internal self-related mentation are disrupted. Specifically, the 'external awareness' network encompassing lateral fronto-temporo-parietal cortices bilaterally, and the 'internal awareness' network including midline anterior cingulate/mesiofrontal and posterior cingulate/precuneal cortices, are functionally disconnected. By contrast, patients in minimally conscious state 'minus', who show non-reflex behaviors, are characterized by right-lateralized recovery of the external awareness network. Similarly, patients who evolve to minimally conscious state 'plus' and respond to commands recover the dominant left-lateralized language network. Now, the use of active experimental paradigms targeting at detecting motor-independent signs of awareness or even establishing communication with these patients, challenge these two clinical boundaries. Such advances are naturally accompanied by legitimate neuroscientific and ethical queries demanding our attention on the medical implementations of this new knowledge. [less ▲]

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See detailOur rapidly changing understanding of acute and chronic disorders of consciousness: challenges for neurologists
Gantner, Sylvia ULg; BODART, Olivier ULg; Laureys, Steven ULg et al

in Future Neurology (2013), 8(1), 43-54

A number of recent studies suggest that some ‘vegetative state’ patients have been misdiagnosed, judging by their ability to follow commands and in some cases even communicate through brain activity. Such ... [more ▼]

A number of recent studies suggest that some ‘vegetative state’ patients have been misdiagnosed, judging by their ability to follow commands and in some cases even communicate through brain activity. Such studies highlight the difficulty in forming a diagnosis based only on behavioral assessments. We think that neuroimaging and electrophysiology methods will be used more frequently in clinical settings, integrated with existing behavioral assessments. Such efforts are expected to lead to a more accurate understanding of individual patients’ cognitive abilities or even provide prognostic indicators. In terms of treatment planning (i.e., pain management and end-of-life decision-making), patients with disorders of consciousness are now offered the possibility of expressing their preferences by means of brain–computer interfaces. What remains to be clarified is the degree to which such indirect responses can be considered reliable and of legal representation. [less ▲]

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See detailThe neuroscience of tinnitus: Perspectives from human neuroimaging studies.
Maudoux, Audrey ULg; Vanneste, Sven; De Ridder, Dirk et al

Conference (2012, November)

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See detailThe neuroscience of tinnitus: Perspectives from human neuroimaging studies
Maudoux, Audrey ULg; Vanneste, Sven; De Ridder, Dirk et al

Conference (2012, November)

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See detailDetecting Consciousness with a Brain-computer Interface
Noirhomme, Quentin ULg; Lesenfants, Damien ULg; Lehembre, Remy ULg et al

in Pons, J. L.; Torricelli, D.; Pajaro, M. (Eds.) Converging Clinical and Engineering Research on Neurorehabilitation (2012, November)

Recent electrophysiological and neuroimaging studies showed command-specific changes in EEG or fMRI signals of unresponsive patients providing motor-independent evidence of conscious thoughts. These ... [more ▼]

Recent electrophysiological and neuroimaging studies showed command-specific changes in EEG or fMRI signals of unresponsive patients providing motor-independent evidence of conscious thoughts. These promising results have paved the way for a new application for Brain-computer Interface (BCI): detecting consciousness in patients with disorders of consciousness (DOC). In the present abstract, we review the first results obtained by BCI-like applications in patients with DOC and discuss the challenges facing BCI research. We believe that patients with DOC may benefit from BCI based diagnosis. BCIs may detect changes in the signal in response to command and, in some cases, may permit communication. [less ▲]

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See detailMemories of Near-Death experiences are they memories of imagined events?
Thonnard, Marie ULg; Charland-Verville, Vanessa ULg; Brédart, Serge ULg et al

Poster (2012, October 27)

Background: The phenomenon of Near-Death Experiences (NDEs) has always intrigued but is still not fully explained despite numerous theories and studies. Since reports of NDEs are proposed to be imagined ... [more ▼]

Background: The phenomenon of Near-Death Experiences (NDEs) has always intrigued but is still not fully explained despite numerous theories and studies. Since reports of NDEs are proposed to be imagined events (French, 2001), and since memories of imagined events have, on average, fewer phenomenological characteristics than real event memories (e.g. Johnson et al., 1988), we here compared phenomenological characteristics of NDEs reports with memories of imagined and real events. Methods: We included 3 groups of coma survivors (8 patients with NDE as defined by the Greyson NDE scale – the “NDE memory group”- , 6 patients without NDE but with memory of their coma – the “coma memory group” – and 7 patients without memories of their coma – the “no memory group”) and a group of 18 age-matched healthy volunteers. Five memories were assessed using Memory Characteristics Questionnaire (MCQ – Johnson et al., 1988): target memory (NDE for NDE memory group, coma memory for coma memory group, and first childhood memory for no memory and control groups), old and recent real event memories and old and recent imagined event memories. Results: In NDE group, NDE memories showd more characteristics than memories of imagined and real events (p<0.02). These memories contain more self-referential and emotional information and have better clarity than memories of coma (all p<0.02). Conclusion: The present study showed that NDE memories contain more characteristics than real event memories and coma memories. Thus, they cannot be considered as classic imagined event memories. On the contrary, their physiological origins could lead them to be really perceived although not lived in the reality. Further work is needed to better understand this phenomenon [less ▲]

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See detailMindsight: Diagnostics in Disorders of Consciousness
Guldenmund, Justus Pieter ULg; Stender, Johan; Heine, Lizette ULg et al

in Critical Care Research and Practice (2012)

Diagnosis of patients with disorders of consciousness (comprising coma, vegetative state/unresponsive wakefulness syndrome, and minimally conscious state) has long been dependent on unstandardized ... [more ▼]

Diagnosis of patients with disorders of consciousness (comprising coma, vegetative state/unresponsive wakefulness syndrome, and minimally conscious state) has long been dependent on unstandardized behavioral tests. The arrival of standardized behavioral tools, and especially the Coma Recovery Scale revised, uncovered a high rate of misdiagnosis. Ancillary techniques, such as brain imaging and electrophysiological examinations, are ever more often being deployed to aid in the search for remaining consciousness. They are used to look for brain activity patterns similar to those found in healthy controls. The development of portable and cheaper devices will make these techniques more widely available. [less ▲]

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See detailInvestigating the tinnitus brain using resting-state fMRI
Maudoux, Audrey ULg; Vanneste, Sven; De Ridder, Dirk et al

Conference (2012, June)

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See detailInvestigating the tinnitus brain using resting-state fMRI.
Maudoux, Audrey ULg; Vanneste, Sven; De Ridder, Dirk et al

Conference (2012, June)

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See detailAuditory Resting-State Network Connectivity in Tinnitus: a Functionnal MRI Study.
MAUDOUX, Audrey ULg; LEFEBVRE, Philippe ULg; CABAY, Jean-Evrard ULg et al

in PLoS ONE (2012)

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 ... [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. [less ▲]

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See detailROLE OF ACTIVE ERP PARADIGMS IN AWARENESS DETECTION IN NON RESPONSIVE PATIENTS
Lugo, Zulay; Lesenfants, Damien ULg; Lehembre, Remy ULg et al

in Proceedings of the 1st international DECODER Workshop (2012, April)

The role of active vs. passive ERP paradigms in disorders of consciousness is assessed in this case study of a LIS patient. Results show that despite absent P3 in a passive auditory task, the patient ... [more ▼]

The role of active vs. passive ERP paradigms in disorders of consciousness is assessed in this case study of a LIS patient. Results show that despite absent P3 in a passive auditory task, the patient displayed significant differences in the active task. This study shows the importance of using a large battery of tests when assessing DOC patients. [less ▲]

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See detailPain perception in disorders of consciousness: Neuroscience, clinical care, and ethics in dialogue
Demertzi, Athina ULg; Racine, Eric; Bruno, Marie-Aurélie ULg et al

in Neuroethics (2012)

Pain, suffering and positive emotions in patients in vegetative state/unresponsive wakefulness syndrome (VS/UWS) and minimally conscious states (MCS) pose clinical and ethical challenges. Clinically, we ... [more ▼]

Pain, suffering and positive emotions in patients in vegetative state/unresponsive wakefulness syndrome (VS/UWS) and minimally conscious states (MCS) pose clinical and ethical challenges. Clinically, we evaluate behavioural responses after painful stimulation and also emotionally-contingent behaviours (e.g., smiling). Using stimuli with emotional valence, neuroimaging and electrophysiology technologies can detect subclinical remnants of preserved capacities for pain which might influence decisions about treatment limitation. To date, no data exist as to how healthcare providers think about end-of-life options (e.g., withdrawal of artificial nutrition and hydration) in the presence or absence of pain in non-communicative patients. Here, we aimed to better clarify this issue by re-analyzing previously published data on pain perception (Prog Brain Res 2009 177, 329–38) and end-of-life decisions (J Neurol 2010 258, 1058–65) in patients with disorders of consciousness. In a sample of 2259 European healthcare professionals we found that, for VS/UWS more respondents agreed with treatment withdrawal when they considered that VS/UWS patients did not feel pain (77%) as compared to those who thought VS/UWS did feel pain (59%). This interaction was influenced by religiosity and professional background. For MCS, end-of-life attitudes were not influenced by opinions on pain perception. Within a contemporary ethical context we discuss (1) the evolving scientific understandings of pain perception and their relationship to existing clinical and ethical guidelines; (2) the discrepancies of attitudes within (and between) healthcare providers and their consequences for treatment approaches, and (3) the implicit but complex relationship between pain perception and attitudes toward life-sustaining treatments. [less ▲]

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See detailPropofol induced unconsciousness: fMRI total neuronal activity and resting state networks.
Gantner, Ithabi; Guldenmund, Justus Pieter ULg; Gómez, Francisco et al

Poster (2012)

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See detailBrain-computer interfacing in disorders of consciousness.
Chatelle, Camille ULg; Chennu, Srivas; Noirhomme, Quentin ULg et al

in Brain Injury (2012), 26(12), 1510-22

Background: Recent neuroimaging research has strikingly demonstrated the existence of covert awareness in some patients with disorders of consciousness (DoC). These findings have highlighted the potential ... [more ▼]

Background: Recent neuroimaging research has strikingly demonstrated the existence of covert awareness in some patients with disorders of consciousness (DoC). These findings have highlighted the potential for the development of simple brain-computer interfaces (BCI) as a diagnosis in behaviourally unresponsive patients. Objectives: This study here reviews current EEG-based BCIs that hold potential for assessing and eventually assisting patients with DoC. It highlights key areas for further development that might eventually make their application feasible in this challenging patient group. Methods: The major types of BCIs proposed in the literature are considered, namely those based on the P3 potential, sensorimotor rhythms, steady state oscillations and slow cortical potentials. In each case, a brief overview of the relevant literature is provided and then their relative merits for BCI applications in DoC are considered. Results: A range of BCI designs have been proposed and tested for enabling communication in fully conscious, paralysed patients. Although many of these have potential applicability for patients with DoC, they share some key challenges that need to be overcome, including limitations of stimulation modality, feedback, user training and consistency. Conclusion: Future work will need to address the technical and practical challenges facing reliable implementation at the patient's bedside. [less ▲]

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See detailNeural correlates of consciousness during general anesthesia using functional magnetic resonance imaging (fMRI).
BONHOMME, Vincent ULg; Boveroux, Pierre; Brichant, Jean-François ULg et al

in Archives italiennes de biologie (2012), 150(2-3), 155-63

This paper reviews the current knowledge about the mechanisms of anesthesia-induced alteration of consciousness. It is now evident that hypnotic anesthetic agents have specific brain targets whose ... [more ▼]

This paper reviews the current knowledge about the mechanisms of anesthesia-induced alteration of consciousness. It is now evident that hypnotic anesthetic agents have specific brain targets whose function is hierarchically altered in a dose-dependent manner. Higher order networks, thought to be involved in mental content generation, as well as sub-cortical networks involved in thalamic activity regulation seems to be affected first by increasing concentrations of hypnotic agents that enhance inhibitory neurotransmission. Lower order sensory networks are preserved, including thalamo-cortical connectivity into those networks, even at concentrations that suppress responsiveness, but cross-modal sensory interactions are inhibited. Thalamo-cortical connectivity into the consciousness networks decreases with increasing concentrations of those agents, and is transformed into an anti-correlated activity between the thalamus and the cortex for the deepest levels of sedation, when the subject is non responsive. Future will tell us whether these brain function alterations are also observed with hypnotic agents that mainly inhibit excitatory neurotransmission. The link between the observations made using fMRI and the identified biochemical targets of hypnotic anesthetic agents still remains to be identified. [less ▲]

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