References of "Laureys, Steven"
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See detailConsciousness and communication BCIs in severe brain-injured patients
Annen, Jitka ULiege; Laureys, Steven ULiege; Gosseries, Olivia ULiege

in Handbook Brain-Computer Interfacing: Neural Devices for paralysis in neurological practise and beyond (in press)

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See detailFrom unconscious to conscious: a spectrum of states
Barra, Alice ULiege; Carrière, Manon ULiege; LAUREYS, Steven ULiege et al

in Overgaard, M; Mogensen, J; Kirkeby-Hinrup, A (Eds.) Beyond the Neural Correlates of Consciousness (in press)

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See detailLes expériences de mort imminente
Cassol, Helena ULiege; Martial, Charlotte ULiege; Laureys, Steven ULiege et al

in MethIS (in press)

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See detailClinical and neuroimaging improvements after apomorphine treatment in a patient with chronic disorders of consciousness following brain hemorrhage
Sanz, Leandro ULiege; Lejeune, Nicolas; Blandiaux, Séverine ULiege et al

in Brain Injury (in press)

Background: There are few available therapeutic options to promote recovery among patients with disorders of consciousness (DOC). Among pharmacological treatments, apomorphine, a dopamine agonist, has ... [more ▼]

Background: There are few available therapeutic options to promote recovery among patients with disorders of consciousness (DOC). Among pharmacological treatments, apomorphine, a dopamine agonist, has exhibited promising behavioral effects in traumatic brain injury. Its efficacy among patients with non-traumatic brain injury has never been documented and its action on brain activity remains unknown. We report the case of a patient with DOC following intracranial hemorrhage, who was treated with apomorphine in a prospective open-label study. Methods/design: A 47-year-old woman with chronic DOC (minimally conscious state; MCS) following spontaneous rupture of a left carotidal aneurysm (132 days since onset), was treated with apomorphine for 30 days. The drug was administered via subcutaneous infusions 12 hours per day, with escalating doses up to 6 mg/h. The patient was monitored 30 days before initiation of therapy, during treatment and 30 days after withdrawal, using the Coma Recovery Scale – Revised (CRS-R). High-density electroencephalography (hdEEG) and fluorodeoxyglucose positron emission tomography (FDG-PET) were acquired before and after treatment. Outcome measures included CRS-R diagnosis, FDG-PET standardized uptake values, a multivariate classifier integrating 68 individual hdEEG markers and hdEEG functional connectivity using debiased weighted phase lag index. Results: Before treatment, CRS-R scores were compatible with a diagnosis of unresponsive wakefulness syndrome (UWS) in 8/9 evaluations, and with a MCS- only once. During treatment, the patient was diagnosed as UWS in 2/8 evaluations, MCS- in 5/8 evaluations and MCS+ once, characterized by the presence of reproducible response to command. After treatment withdrawal, she was diagnosed UWS once and MCS- in 4/5 evaluations. Compared to 54 healthy controls, FDG-PET whole brain metabolism revealed a 59% metabolic drop before treatment and 51% after treatment, with increases in right temporal, parietal and frontal cortical areas. The multivariate classifier using resting-state hdEEG data was in favor of a UWS before treatment, while it indicated a MCS after treatment. Most of the individual markers increased after treatment, including alpha and beta spectral power, spectral entropy, Kolmogorov complexity and permutation entropy. Functional connectivity analyses also indicated an increase in network centrality predominant in the alpha frequency band after treatment compared to before treatment. Discussion: After treatment with apomorphine, this patient showed improvements both at the clinical and neuroimaging levels. While signs of consciousness were only observed once at baseline, most of the assessments performed during and after treatment led to a diagnosis of MCS. Notably, a reproducible response to command was observed once during treatment, leading to a change of diagnosis. Brain activity measures all increased after treatment compared to before treatment. These multimodal improvements suggest that apomorphine may be efficient to promote the recovery of non-traumatic DOC patients, and that its action can be measured through different changes in brain imaging markers. Clinical trial identifiers: EudraCT 2018-003144-23; Clinicaltrials.gov NCT03623828 [less ▲]

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See detailStudy of the impact of non-pharmacological techniques (self-hypnosis/self-care) on cognitive complaints in cancer patients
Bicego, Aminata Yasmina ULiege; Grégoire, Charlotte; Cassol, Helena ULiege et al

Conference (2019, May 30)

Cancer diagnosis generates a number of physical, psychological and cognitive impairments such as memory, attentional and informational processing deficits that can undermine patients’ quality of life (QoL ... [more ▼]

Cancer diagnosis generates a number of physical, psychological and cognitive impairments such as memory, attentional and informational processing deficits that can undermine patients’ quality of life (QoL). Self-hypnosis combined to self-care learning have been used in the past years to treat these symptoms, at the moment of diagnosis, during and/or after the cancer treatments. However, the impact of self-hypnosis/self-care upon cognitive difficulties has not been investigated yet.The aim of this study is to better understand the impact of self hypnosis/self-care upon the cognitive functions by means of the Functional Assessment of Cancer Therapy-Cognitive Function1 (FACT-COG). [less ▲]

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See detailThe impact of non-pharmacological approaches on the patient’s comfort after a cardiac surgery: A randomized controlled trial.
Rousseaux, Floriane ULiege; Puttaert, Ninon ULiege; LEDOUX, Didier ULiege et al

Conference (2019, May 30)

Different non-pharmacological techniques including hypnosis, music, and virtual reality (VR) are being used as complementary tools in the treatment of pain. A new technique which encompasses a combination ... [more ▼]

Different non-pharmacological techniques including hypnosis, music, and virtual reality (VR) are being used as complementary tools in the treatment of pain. A new technique which encompasses a combination of hypnosis and VR, called "virtual reality hypnosis" (VRH), should soon be used on a regular basis in clinical settings. The aim of this study is to better understand the impact of hypnosis, music, VR and VRH, and to investigate their influence on the patient’s perception of pain, anxiety and tiredness after a cardiac surgery in intensive care unit [less ▲]

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See detailDiagnostic accuracy of a CRS-R modified score in patients with disorders of consciousness.
Annen, Jitka ULiege; Filippini, Maria Maddalena ULiege; Bonin, Estelle ULiege et al

in Brain Injury (2019, March 16)

Introduction The Coma Recovery Scale-Revised (CRS-R) is the gold standard diagnostic tool for assessing patients with disorders of consciousness (DOC) after severe acquired brain injury (Giacino, Kalmar ... [more ▼]

Introduction The Coma Recovery Scale-Revised (CRS-R) is the gold standard diagnostic tool for assessing patients with disorders of consciousness (DOC) after severe acquired brain injury (Giacino, Kalmar and Whyte, 2004; Seel et al., 2010). Differential diagnosis of DOC includes the unresponsive wakefulness syndrome (UWS;(Laureys et al., 2010)), characterized by the recovery of eye-opening but no behavioral evidence of self or environmental awareness, and the minimally conscious state (MCS; (Giacino et al., 2002)) defined by clearly discernible but inconsistent behavioral signs of conscious awareness. The CRS-R assesses reflexes and cognitively mediated behavior in six domains, namely auditory (4 items), visual (5 items), motor (6 items), oromotor (3 items), communication (2 items) and arousal (3 items). Items in every subscale are hierarchically ordered (i.e. reflexive to cognitively-mediated behaviors; higher level behaviors correspond to higher level of neurologic functioning and ability to demonstrate lower-level behaviors or disappearance of pathological behaviors as sign of recovery) and can be used to infer the patient’s level of consciousness (La Porta et al., 2013; Gerrard, Zafonte and Giacino, 2014). Several studies on DOC investigating markers of consciousness, recovery and treatment used the CRS-R total score (i.e. addition of the highest scores reached for each subscale) as regressor in neuroimaging analyses (Bruno et al., 2012; Thibaut et al., 2012; Margetis et al., 2014; Bagnato et al., 2015). However, ignoring the hierarchy of the subscales in the CRS-R total score reduces the sensitivity for the diagnosis of MCS patients (i.e., 100% specificity for UWS but false negative diagnostic error of 22%, with a cut-off CRS-R total score of 10 (Bodien et al., 2016)). In addition, the ordinal nature of the CRS-R total score make it limited to use with parametric statistical tests (e.g., requiring normal distribution). A solution to this problem has been proposed by Sattin and colleagues (2015) who computed a CRS-R modified score (CRS-R MS1), by considering reflexes and cognitively mediated behaviors separately, reliably distinguishing between UWS and MCS patients. These authors also argue that the interpretation of the total CRS-R scores is limited due to “the underlying assumption that if a patient is able to show higher-level behaviors, he/she is also able to show lower-level responses”. Sattin et al. (2015) propose to account for the number of presented responses in every subscale (i.e., every items in a subscale should be assessed and scored). One major drawback to this approach is that according to the CRS-R guidelines, the assessor should start assessing the highest item and move to the next subscale once an item is scored, in line with the hierarchical organization of the scale. This means that, if the CRS-R is performed according to the guidelines (for which the CRS-R has been validated), the CRS-R modified score cannot be calculated. Even if assessing all items might be valid, it is unlikely to be done in many clinical and research settings as it would increase assessment time and fatigue the patient. We here propose to adapt the CRS-R MS1 by considering only the highest score reached on every subscale, respecting the CRS-R guidelines. Methods One-hundred twenty-four patients admitted to the University Hospital of Liège were assessed multiple times with the CRS-R, at least once including the assessment of all items. Patients for whom the CRS-R assessment including all items provided the same diagnosis as the patient’s final diagnosis were selected. The study was approved by the ethics committee of the University Hospital of Liège and the legal guardians of patients gave written informed consent for participation in the study, in accordance with the Declaration of Helsinki. The CRS-R total score and two CRS-R MS were calculated for every patient. The CRS-R MS combines scores for reflexes and cognitive behaviors of every CRS-R subscale which can be used to obtain the CSR-R MS from a transposition matrix. The CRS-R MS1 was calculated as previously described (Sattin et al., 2015), and the CRS-R MS2 only used the highest score in every subscale (i.e., assuming that lower items were successful). Statistics were performed in R (R Core team, 2012). We assessed group differences in age (two sample t-test), time since injury (two sample t-test) and etiology (χ2 test). Receiver Operating Characteristic were calculated to obtain the sensitivity and specificity at several classification thresholds (package pROC (Robin et al., 2011)). We calculated the correlation between the CRSR MS1 and CRSR MS2 using Pearson correlation, and both scores with the CRS-R total score using Spearman correlation. Finally, we used a Kolmogorov-Smirnoff test to evaluate whether CRSR MS1 and CRSR MS2 come from different distributions (i.e., if one approach provides additional information over the other). Results Eighty-five MCS patients (26 females; mean age 40.4 (SD±17.4) years old; 43 traumatic; mean time since injury 2.7 (SD±4.0) years) and 39 UWS patients (14 females; mean age 50.6 (SD±16.5) years old; 29 traumatic; mean time since injury 1.2 (SD±1.8) years) were included in the study. MCS patients were older (t(77.6)-3.15, p<0.002 95%CI[-16.7, -3.7]), were in a more chronic stage (t(121.9)=2.9, p = 0.005, 95%CI[974,427]), and suffered more often from a traumatic brain injury (χ2=6.8, p = 0.01) than UWS patients. The ROC analysis for both MS showed an AUC of 1 (cut-off:8.315, 100% specificity and sensitivity). The ROC analysis for the CRS-R total score showed an AUC of 0.94 (cut-off:9, sensitivity = 100%, specificity = 67%). A correlation was found between the CRSR total score and both the CRSR MS1 (r = 0.94, p < 0.0001, figure 1A) and CRSR MS2 (r = 0.96, p < 0.0001, figure 1B). The two CRS-R MS correlated (r = 0.96, p = 0.0001, figure 1C). CRSR MS1 and CRSR MS2 were drawn from the same distribution (D(124)= 0.13, p = 0.25). Discussion CRSR MS2 correlated strongly with the CRSR MS1, and perfectly discriminated UWS from MCS patients. As for accurate diagnosis the CRS-R should be repeated (preferably five times (Wannez et al., 2018)) short assessments are preferred, and possibly also reduce effects of fatigue. Second, the CRSR MS2 can be calculated with CRS-R assessments performed according to the CRS-R guidelines, facilitating its use in clinical environments, and in research settings where CRSR MS2 can be used pro- and retrospectively for research protocols. Furthermore, the results indicate that the two modified scores share the same distribution. This suggests that assessing all CRS-R items as proposed previously does not significantly contribute to the stratification of patients. The CRSR MS2 code is available via: Github A remaining limitation of the proposed score is that it does not allow to distinguish MCS minus (i.e. showing language independent signs of awareness, like visual pursuit) from MCS plus (i.e. showing language dependent signs of awareness) patients, or emergence from MCS. However, a clear consensus about the diagnostic criteria is needed before an updated modified score can be provided. In conclusion, the current analyses show that the calculation of the CRS-R modified score using the highest item in every subscale is valid for clinical diagnosis, and provides perspective for its use for research. Figure Figure 1. Correlation between the CRS-R total score and the CRS-R MS1 (1A), CRSR MS2 (1B), and between the two modified CRS-R scores (1C). MCS plus patients are here characterized by command following, intelligible verbalization and/or intentional communication. Acknowledgements This project has received funding from the University and University Hospital of Liege, the Belgian National Funds for Scientific Research (FRS-FNRS), the European Union’s Horizon 2020 Framework Programme for Research and Innovation under the Specific Grant Agreement No. 785907 (Human Brain Project SGA2) the Luminous project (EU-H2020-fetopenga686764), the Center-TBI project (FP7-HEALTH- 602150), the Public Utility Foundation ‘Université Européenne du Travail’, “Fondazione Europea di Ricerca Biomedica”, the Bial Foundation, the Mind Science Foundation and the European Commission, the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 778234, European Space Agency (ESA) and the Belgian Federal Science Policy Office (BELSPO) for their support in the framework of the PRODEX Programme. CC is a post-doctoral Marie Sklodowska-Curie fellow (H2020-MSCA-IF-2016-ADOC-752686), and SL is research director at FRS-FNRS. We are highly grateful to the members of the Liège Coma Science Group for their assistance in clinical evaluations, and we thank all the patients and their families and the Neurology department of the University hospital of Liège. [less ▲]

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See detailIs auditory localization a sign of consciousness? Evidence from neuroimaging and electrophysiology
Carrière, Manon ULiege; Cassol, Helena ULiege; Aubinet, Charlène ULiege et al

Conference (2019, March 16)

Background Auditory localization is often part of the clinical evaluation of patients recovering from coma. There is however no clear consensus whether it should be considered as a reflex or as a ... [more ▼]

Background Auditory localization is often part of the clinical evaluation of patients recovering from coma. There is however no clear consensus whether it should be considered as a reflex or as a conscious behavior. For example, auditory localisation corresponds to the diagnosis of unresponsive wakefulness syndrome (UWS) in the Coma Recovery Scale-Revised, while it is considered a sign of consciousness in other post-coma scales. This study aims to determine if auditory localization reflects conscious processing in patients with disorders of consciousness. Methods We first evaluated the proportion of patients with and without auditory localisation in 186 patients with severe brain injury, including 64 UWS, 28 minimally conscious minus (MCS-), 71 minimally conscious plus (MCS+), i.e., language relatively preserved) and 23 who emerged from MCS (EMCS). We then measured brain metabolism using fluorine-18 fluorodeoxyglucose positron emission tomography, functional connectivity using magnetic resonance imaging (MRI) and high-density electroencephalography (EEG) in patients in UWS with and without auditory localization. Findings Auditory localization was observed in 12% of patients in UWS, 46% of patients in MCS-, 62% of patients in MCS+ and 78% of patients in EMCS. Brain metabolism of patients in UWS without auditory localization was mostly restricted to primary areas, whereas a more widespread activity, including associative areas, was observed in patients in UWS with auditory localisation. Brain functional connectivity was also higher in patients in UWS with auditory localisation in the frontoparietal fMRI resting state network, along with higher EEG connectivity in alpha frequency band, compared to patients without auditory localization. Finally, differences were also found regarding the outcome, as the survival rate at two years appeared to be significantly higher in UWS patients with auditory localization as compared to those without auditory localization. Interpretation. Both clinical data in post-comatose patients and neuroimaging examinations in UWS patients with and without auditory localization support the idea that auditory localization should be considered as a sign of consciousness. [less ▲]

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See detailNeurophysiological effects and behavioral outcomes after tPCS and tDCS in a patient in minimally conscious state
Barra, Alice ULiege; Mortaheb, Sepehr ULiege; Carrière, Manon ULiege et al

Conference (2019, March 15)

Introduction: Non-invasive brain stimulation (NIBS)(1-4) is a promising path in the search for treatments of patients with disorders of consciousness (DOC). Transcranial pulsed-current stimulation (tPCS ... [more ▼]

Introduction: Non-invasive brain stimulation (NIBS)(1-4) is a promising path in the search for treatments of patients with disorders of consciousness (DOC). Transcranial pulsed-current stimulation (tPCS) has been used to modulate cortical and subcortical neural connectivity within 6-10Hz(5). It was successfully employed to enhance motor and cognitive functions in healthy volunteers (6) and it is theoretically able to reach deeper brain structures(7) . On the other hand, transcranial direct-current stimulation (tDCS) over left dorsolateral prefrontal cortex (DLPFC) has shown to improve cognitive functions in DOC patients as measured by the Coma Recovery Scale-Revised (CRS-R) in about 50% of patients in minimally conscious state (MCS) (8,9). These are preliminary results of an ongoing study that aim to investigate the effects of tPCS and tDCS on one patient with DOC. Methods: This was a randomized double-blind sham-controlled clinical trial on a patient with DOC. The Subject received 3 sessions of stimulation: active tPCS sham tDCS, sham tPCS with active tDCS, and sham tPCS with sham tDCS. Before and after each session we evaluated the patient with the CRS-R and recorded 10 minutes of resting EEG. The stimulation target for tPCS was the bimastoid line with a random frequency of 6-10Hz (2mA peak to peak), whereas the target for tDCS was the left DLPFC with 2mA of intensity. EEG data were pre-processed and the power of signal was calculated for each frequency band: Delta (0-4 Hz), Theta (4-8 Hz), Alpha (8-12 Hz) and Beta (12-25 Hz). A non-parametric corrected cluster permutation test(10) was used to statistically compare the power maps before and after each session. Electrode clusters with p-value below 0.01 were considered as significantly different. Results and Discussion: An increase of Alpha and Beta power and decrease of Theta and Delta power was observed after anodal tDCS together with an increase of behavioural responsiveness as measured by the CRS-R score. After active tPCS, a significant increase was observed in Theta power consistently with the frequency of the stimulation (6-10Hz). However, this increase did not result in any measurable behavioural improvement maybe due to insufficient number of sessions or inadequate frequency of stimulation. Nevertheless, it could be relevant to mention that the patient’s caregivers noticed longer periods of wakefullness and higher arousal after tPCS. Therefore, it may be hypothesized that the CRS-R was not sensitive enough to capture these behavioural changes. Conclusion: In conclusion, here tDCS and tPCS induced distinct neurophysiological and clinical effects. So far, tDCS seems to be confirmed as a promising tool to improve behavioural responsiveness of patients with DOC. On the other hand, tPCS should be explored in larger cohorts to understand if this type of stimulation can reach similar results as the ones observed for tDCS. [less ▲]

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See detailInternational validation of the Phone Outcome Questionnaire for patients with Disorders Of Consciousness
Wolff, Audrey ULiege; Estraneo, Anna; Noé, Quique et al

Poster (2019, March 15)

Assessing the evolution of severely brain-injured patients with disorders of consciousness (DOC) with current tools like the Glasgow Outcome Scale-Extended (GOS-E) remains a challenge. At the bedside, the ... [more ▼]

Assessing the evolution of severely brain-injured patients with disorders of consciousness (DOC) with current tools like the Glasgow Outcome Scale-Extended (GOS-E) remains a challenge. At the bedside, the most reliable diagnostic tool is currently the Coma Recovery Scale-Revised. The CRS-R distinguishes patients with unresponsive wakefulness syndrome (UWS) from patients in minimally conscious state (MCS) and patients who have emerged from MCS (EMCS). This international multi-centric study aims to validate a phone outcome questionnaire (POQ) based on the CRS-R and compare it to the CRS-R performed at the bedside and to the GOS-E which evaluates the level of disability and assigns patient’s in outcomes categories. The POQ will allow clinicians to probe the evolution of patient’s state of consciousness based on caregivers feedback. This research project is part of the International Brain Injury Association, Disorders of Consciousness-Special Interest Group (DOCSIG) and DOCMA consortium. [less ▲]

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See detailPupil diameter and Behavioral Responsiveness in Disorders of Consciousness
Mortaheb, Sepehr ULiege; Bonin, Estelle ULiege; Laureys, Steven ULiege et al

Poster (2019, March 15)

The clinical diagnosis of consciousness is mainly based on bedside observation of the patient's responses using standardized neurobehavioral scales. By definition, it is common to observe vigilance ... [more ▼]

The clinical diagnosis of consciousness is mainly based on bedside observation of the patient's responses using standardized neurobehavioral scales. By definition, it is common to observe vigilance fluctuation in patients in minimally conscious state (MCS) who would show reproducible but fluctuating signs of consciousness [1]. As the probability to detect voluntary responses depends on the patient's level of vigilance at the time of assessment, multiple assessments are needed in order to detect signs of consciousness and avoid misdiagnosis [2]. If this fluctuation is known in disorders of consciousness (DOC), it remains poorly understood and characterized. In this study, we investigated the relationship between pupil diameter (suggested as an objective physiological measure of alertness level in healthy subjects [3-6]) and behavioral responsiveness in DOC patients. To this end, five patients with chronic DOC (1 unresponsive wakefulness syndrome [UWS; ie, reflexive responses], 2 MCS- [ie, signs of consciousness but no signs of language preservation, 2 MCS+ [ie, signs of language preservation]; 3 males; age=47±15.16 (median ± SD), median TSI=284 days) were enrolled. For each patient, four behavioral assessments were performed in a single day using the Coma Recovery Scale-Revised. Before each assessment, pupil response was recorded for 10 minuttients (MCS-) was excluded from the analysis due to eye closure during whole recording period. Pupil diameter was recorded using Phasya Drowsimeter R100 glasses (eye images acquired at 120 Hz with a high-speed camera integrated into the glasses). Eye closure periods were marked manually. Several parameters were investigated: eye opening percentage (EOP), as well as median, variance, entropy, and Lempel-Ziv complexity of the pupil diameter. We here provide preliminary descriptive results for this small sample. We observed lower EOP and median pupil diameter when the patients were unresponsive (i.e., diagnosis of UWS) vs. when they were responsive at bedside (i.e., MCS; median EOP=74.78% vs 99.6%, median pupil diameter=21 vs 28). Variance did not show any specific pattern; however, complexity measures of entropy and Lempel-Ziv were also lower in the UWS (median entropy=9.83 vs 10.58 and median Lempel-Ziv complexity=121 vs 328). Median pupil diameter also seemed to be more sensitive to behavioural changes across different assessments. These preliminary data suggest that higher responsiveness is related to higher median and complexity of the pupillometry signal and eye opening percentage at rest, supporting that pupillometry markers could be used as potential predictor of behavioral responsiveness in DOC patients. [less ▲]

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See detailNociception Coma Scale Revised allows to identify patients with preserved neural basis for pain experience.
Bonin, Estelle ULiege; Lejeune, Nicolas; Thibaut, Aurore ULiege et al

Poster (2019, March 14)

The Nociception Coma Scale-Revised (NCS-R) was developed to help assessing pain in non-communicative patients with disorders of consciousness (DOC). Several studies have shown its sensitivity in assessing ... [more ▼]

The Nociception Coma Scale-Revised (NCS-R) was developed to help assessing pain in non-communicative patients with disorders of consciousness (DOC). Several studies have shown its sensitivity in assessing responses to acute noxious stimuli. However, they failed to determine a reliable cut-off score that could be used to infer pain processing in these patients. This retrospective cross-sectional study aimed to determine an NCS-R cut-off score supporting preserved neural basis for pain experience, based on brain metabolism as measured by fluorodeoxyglucose positron emission tomography (FDG-PET). We included FDG-PET confirmed patient with unresponsive wakefulness syndrome (UWS) (n=13) and looked at their highest NCS-R total scores. As the highest score was 4, we determined the cut-off of 5 and compared the brain metabolism of these patients with matched DOC patients with a cut-off score ≥ 5 (i.e., potential pain) and healthy controls. We found a higher global cerebral metabolism in healthy subjects compared with both patients’ groups and also in patients with potential pain compared with FDG-PET confirmed UWS. We observed a preserved metabolism in the left insula in patients with potential pain when compared with FDG-PET confirmed UWS. We also found a preservation of the connectivity between the left insula and the medial frontal gyrus in patients with potential pain compared with FDG-PET confirmed UWS. Our data suggest that using the cut-off score of 5 can be helpful to improve pain management in DOC patients. Future studies should focus on patients showing scores below this cut-off to better characterize their profile and improve cares. [less ▲]

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See detailMemories of near-death experiences: are they self-defining?
Cassol, Helena ULiege; D'Argembeau, Arnaud ULiege; Charland-Verville, Vanessa ULiege et al

in Neuroscience of Consciousness (2019), 5(1),

Some people report memories of near-death experiences (NDEs) after facing situations of impending death and these memories appear to have significant consequences on their lives (here referred to as “real ... [more ▼]

Some people report memories of near-death experiences (NDEs) after facing situations of impending death and these memories appear to have significant consequences on their lives (here referred to as “real NDE experiencers”; real NDErs). We assessed to what extent NDE memories are considered self-defining: memories that help people to define clearly how they see themselves. We screened 71 participants using the Greyson NDE scale (48 real NDErs and 23 NDErs-like who had lived a similar experience in absence of a threat to their life). Participants described their two main self-defining memories (SDMs). For each SDM, they completed the Centrality of Event Scale (CES) to assess how central the event is to their identity. The two subgroups did not differ regarding the proportion of NDErs who recalled their NDE (30 real NDErs out of 48 and 11 NDErs-like out of 23). Real NDErs and NDErs-like who recalled their NDE (n ¼ 41) reported richer experiences as assessed by the Greyson NDE scale. Furthermore, these participants rated their NDE memory as more central to their identity as compared to other SDMs, and the richness of the NDE memory was positively associated to its centrality (CES scores). Overall, these findings suggest that the self-defining aspect of the experience might be related to its phenomenological content rather than its circumstances of occurrence. The self-defining status of NDE memories confirms that they constitute an important part of NDErs’ personal identity and highlights the importance for clinicians to facilitate their integration within the self. [less ▲]

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See detailNeurochemical models of near-death experiences: a large-scale study based on the semantic similarity of written reports
Martial, Charlotte ULiege; Cassol, Helena ULiege; Charland-Verville, Vanessa ULiege et al

in Consciousness and Cognition (2019)

The real or perceived proximity to death often results in a non-ordinary state of consciousness characterized by phenomenological features such as the perception of leaving the body boundaries, feelings ... [more ▼]

The real or perceived proximity to death often results in a non-ordinary state of consciousness characterized by phenomenological features such as the perception of leaving the body boundaries, feelings of peace, bliss and timelessness, life review, the sensation of traveling through a tunnel and an irreversible threshold. Near-death experiences (NDEs) are comparable among individuals of different cultures, suggesting an underlying neurobiological mechanism. Anecdotal accounts of the similarity between NDEs and certain drug-induced altered states of consciousness prompted us to perform a large-scale comparative analysis of these experiences. After assessing the semantic similarity between ≈15,000 reports linked to the use of 165 psychoactive substances with 625 NDE narratives, we determined that the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine consistently resulted in reports most similar to those associated with NDEs. Ketamine was followed by Salvia divinorum (a plant containing a potent and selective κ receptor agonist) and a series of serotonergic psychedelics, including the endogenous serotonin 2A receptor agonist N,N Dimethyltryptamine (DMT). This similarity was driven by semantic concepts related to consciousness of the self and the environment, but also by those associated with the therapeutic, ceremonial and religious aspects of drug use. Our analysis sheds light on the long-standing link between certain drugs and the experience of “dying“, suggests that ketamine could be used as a safe and reversible experimental model for NDE phenomenology, and supports the speculation that endogenous NMDA antagonists with neuroprotective properties may be released in the proximity of death. [less ▲]

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See detailLinks between the level of consciousness and swallowing: what can we learn from patients in altered states of consciousness?
MELOTTE, Evelyne ULiege; MAUDOUX, Audrey ULiege; DELHALLE, Sabrina ULiege et al

in Abstract Book - IBIA 2019 (2019, March)

Introduction: The aims of this study were to document the extent and characteristics of dysphagia in patients with disorders of consciousness (DOC) and to evaluate the link between consciousness and ... [more ▼]

Introduction: The aims of this study were to document the extent and characteristics of dysphagia in patients with disorders of consciousness (DOC) and to evaluate the link between consciousness and different components of swallowing. Method: We collected and analyzed 10 criteria in link with oral-feeding, respiratory status and Fiberoptic Endoscopic Evaluation of Swallowing (FEES) in 103 DOC patients (43 women; mean age 39±13years) admitted consecutively to the University Hospital of Liege (Belgium) for a one-week multimodal assessment of consciousness. The inclusion criteria were: to have had a coma and severe acquired brain injury, to have performed a FEES, and to have a diagnosis of DOC (unresponsive wakefulness syndrome (UWS)1 or minimally conscious state (MCS)2) confirmed by at least 5 assessments with the Coma Recovery Scale-Revised3 and by positron emission tomography (presence or absence of metabolic activity in the fronto-parietal network bilaterally). We performed a univariate logistic regression between several swallowing related parameters and consciousness diagnosis (UWS or MCS). Logistic regression was adjusted for age, time since insult and etiology. Results: Thirty-one patients were UWS (13 females, 11 with traumatic etiology, 16 post-anoxic and 4 others; 25±23 months post-insult) and 72 were MCS (30 females, 43 from traumatic brain injury, 12 post-anoxic and 17 others; 40±34 months post-insult). Compared with MCS patients, UWS patients had more frequently a tracheotomy still in place (68% UWS vs 24% MCS, p=0.002), pharyngo-laryngeal secretions (60% UWS vs 28% MCS, p=0.032), salivary aspiration (39% UWS vs 13% MCS, p=0.039) and the absence of an efficient oral phase (lip prehension, lingual propulsion and the absence of buccal stasis after swallowing) (0% UWS vs 62% MCS, p=0.003). The other observed parameters (i.e., the presence of an exclusive enteral-feeding, poor sensibility in the pharyngo-laryngeal area, hypertonia of the jaw muscles, basic oral phase of swallowing and thick/liquid aspiration) were not significantly influenced by the level of consciousness in our cohort. Conclusion: some components of swallowing correlate with the level of consciousness in our population of patients with DOC, particularly the efficacy of the oral phase of swallowing. This criterion should be considered as a sign of consciousness, and consequently, it should be taken into account in the diagnosis of DOC. The study also emphasizes the severity of dysphagia in DOC population and highlights the importance of correctly managing these disorders. 1 Bruno et al. (2011). From unresponsive wakefulness to minimally conscious PLUS and functional locked-in syndromes: recent advances in our understanding of disorders of consciousness. Journal of Neurology, 258(7), 1373-1384. 2 Giacino et al. (2002). The minimally conscious state: definition and diagnostic criteria. Neurology, 58(3), 349-353. 3 Giacino et al. (2004) The JFK Coma recovery scale-revised: measurement characteristics and diagnostic utility. Arch Phys Med Rehabil, 85, 2020–2029. 4 Bodart et al. (2017) Measures of metabolism and complexity in the brain of patients with disorders of consciousness. NeuroImage: Clinical, 14, 354‑362. [less ▲]

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See detailHuman consciousness is supported by dynamic complex patterns of brain signal coordination
Demertzi, Athina ULiege; Tagliazucchi, Enzo; Dehaene, S et al

in Science Advances (2019), 5(2), 7603

Adopting the framework of brain dynamics as a cornerstone of human consciousness, we determined whether dynamic signal coordination provides specific and generalizable patterns pertaining to conscious and ... [more ▼]

Adopting the framework of brain dynamics as a cornerstone of human consciousness, we determined whether dynamic signal coordination provides specific and generalizable patterns pertaining to conscious and unconscious states after brain damage. A dynamic pattern of coordinated and anticoordinated functional magnetic resonance imaging signals characterized healthy individuals and minimally conscious patients. The brains of unresponsive patients showed primarily a pattern of low interareal phase coherence mainly mediated by structural connectivity, and had smaller chances to transition between patterns. The complex pattern was further corroborated in patients with covert cognition, who could perform neuroimaging mental imagery tasks, validating this pattern’s implication in consciousness. Anesthesia increased the probability of the less complex pattern to equal levels, validating its implication in unconsciousness. Our results establish that consciousness rests on the brain’s ability to sustain rich brain dynamics and pave the way for determining specific and generalizable fingerprints of conscious and unconscious states. [less ▲]

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See detailClinical and electrophysiological investigation of spastic muscle overactivity in patients with disorders of consciousness following severe brain injury
Martens, Géraldine ULiege; Deltombe, Thierry; Foidart-Dessalle, Marguerite ULiege et al

in Clinical Neurophysiology (2019), 130(2),

Objective The clinical and electrophysiological profile of spastic muscle overactivity (SMO) is poorly documented in patients with disorders of consciousness (DOC) following severe cortical and ... [more ▼]

Objective The clinical and electrophysiological profile of spastic muscle overactivity (SMO) is poorly documented in patients with disorders of consciousness (DOC) following severe cortical and subcortical injury. We aim at investigating the link between the clinical observations of SMO and the electrophysiological spastic over-reactivity in patients with prolonged DOC. Methods We prospectively enrolled adult patients with DOC at least 3 months post traumatic or non-traumatic brain injury. The spastic profile was investigated using the Modified Ashworth Scale and the Hmax/Mmax ratio. T1 MRI data and impact of medication were analyzed as well. Results 21 patients were included (mean age: 41 ± 11 years; time since injury: 4 ± 5 years; 9 women; 10 traumatic etiologies). Eighteen patients presented signs of SMO and 11 had an increased ratio. Eight patients presented signs of SMO but no increased ratio. We did not find any significant correlation between the ratio and the MAS score for each limb (all ps > 0.05). The presence of medication was not significantly associated with a reduction in MAS scores or Hmax/Mmax ratios. Conclusions In this preliminary study, the Hmax/Mmax ratio does not seem to reflect the clinical MAS scores in patients with DOC. This supports the fact they do not only present spasticity but other forms of SMO and contracture. Significance Patients with DOC are still in need of optimized tools to evaluate their spastic profile and therapeutic approaches should be adapted accordingly. [less ▲]

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See detailImproving responsiveness to non-invasive brain stimulation in minimally conscious state patients: a closed-loop approach
Martens, Géraldine ULiege; Barra, Alice ULiege; Carrière, Manon ULiege et al

Poster (2019, February)

Transcranial direct current stimulation (tDCS) applied on the left dorsolateral prefrontal cortex has already been shown to efficiently promote the recovery of conscious awareness in patients with ... [more ▼]

Transcranial direct current stimulation (tDCS) applied on the left dorsolateral prefrontal cortex has already been shown to efficiently promote the recovery of conscious awareness in patients with disorders of consciousness following severe brain injury, especially those in minimally conscious state (MCS)1. However, one potential barrier to clinically respond to tDCS is accounting for the timing of the stimulation with regard to the fluctuations of vigilance that characterize this population2. Indeed, the vigilance of MCS patients has periodic average cycles of 70 minutes (range 57-80 minutes)3, potentially preventing them to be in an optimal neural state to benefit from tDCS when applied at random moments. To tackle this issue, we propose a new protocol to optimize the application of tDCS by selectively stimulating at high vigilance and low vigilance states, as measured by real-time spectral entropy (as a marker of vigilance3) and based on pre-identified individual thresholds, in a closed-loop fashion. We will conduct a clinical trial on 36 patients in MCS who will undergo a 4-hour EEG recording beforehand to set individual vigilance thresholds. The patients will then be randomized in three groups based on the moment of tDCS application: high vigilance, low vigilance and sham. These EEG-tDCS sessions will last for 6 hours with a maximum of two tDCS sessions of 20 min at 2 mA. Behavioral effects will be assessed using the Coma Recovery Scale-Revised4 at baseline, after 3 and 6 hours. The device used will be provided by Starlab and enable real-time analysis of EEG dynamics and spectral entropy as well as control of the tDCS stimulator (a customized version of Neuroelectrics’ Startsim 8). This unique and novel approach will provide new insights for the identification of tDCS responders and provide treatment options for the challenging population of patients with disorders of consciousness. [less ▲]

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