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See detailDetection of response to command using voluntary control of breathing in disorders of consciousness
Charland-Verville, Vanessa ULg; Lesenfants, Damien; Sela, Lee et al

in Frontiers in Human Neuroscience (2014), 8(1020),

BACKGROUND: Detecting signs of consciousness in patients in a vegetative state/unresponsive wakefulness syndrome (UWS/VS) or minimally conscious state (MCS) is known to be very challenging. Plotkin et al ... [more ▼]

BACKGROUND: Detecting signs of consciousness in patients in a vegetative state/unresponsive wakefulness syndrome (UWS/VS) or minimally conscious state (MCS) is known to be very challenging. Plotkin et al. (2010) recently showed the possibility of using a breathing-controlled communication device in patients with locked in syndrome. We here aim to test a breathing-based "sniff controller" that could be used as an alternative diagnostic tool to evaluate response to command in severely brain damaged patients with chronic disorders of consciousness (DOC). METHODS: Twenty-five DOC patients were included. Patients' resting breathing-amplitude was measured during a 5 min resting condition. Next, they were instructed to end the presentation of a music sequence by sniffing vigorously. An automated detection of changes in breathing amplitude (i.e., >1.5 SD of resting) ended the music and hence provided positive feedback to the patient. RESULTS: None of the 11 UWS/VS patients showed a sniff-based response to command. One out of 14 patients with MCS was able to willfully modulate his breathing pattern to answer the command on 16/19 trials (accuracy 84%). Interestingly, this patient failed to show any other motor response to command. DISCUSSION: We here illustrate the possible interest of using breathing-dependent response to command in the detection of residual cognition in patients with DOC after severe brain injury. [less ▲]

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See detailChanges in cerebral metabolism in patients with a minimally conscious state responding to zolpidem.
Chatelle, Camille ULg; Thibaut, Aurore ULg; Gosseries, Olivia ULg et al

in Frontiers in Neuroscience (2014)

BACKGROUND: Zolpidem, a short-acting non-benzodiazepine GABA agonist hypnotic, has been shown to induce paradoxical responses in some patients with disorders of consciousness (DOC), leading to recovery of ... [more ▼]

BACKGROUND: Zolpidem, a short-acting non-benzodiazepine GABA agonist hypnotic, has been shown to induce paradoxical responses in some patients with disorders of consciousness (DOC), leading to recovery of arousal and cognitive abilities. We here assessed zolpidem-induced changes in regional brain metabolism in three patients with known zolpidem response in chronic post-anoxic minimally conscious state (MCS). METHODS: [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) and standardized clinical assessments using the Coma Recovery Scale-Revised were performed after administration of 10 mg zolpidem or placebo in a randomized double blind 2-day protocol. PET data preprocessing and comparison with a healthy age-matched control group were performed using statistical parametric mapping (SPM8). RESULTS: Behaviorally, all patients recovered functional communication after administration of zolpidem (i.e., emergence from the MCS). FDG-PET showed increased metabolism in dorsolateral prefrontal and mesiofrontal cortices after zolpidem but not after placebo administration. CONCLUSION: Our data show a metabolic activation of prefrontal areas, corroborating the proposed mesocircuit hypothesis to explain the paradoxical effect of zolpidem observed in some patients with DOC. It also suggests the key role of the prefrontal cortices in the recovery of functional communication and object use in hypoxic patients with chronic MCS. [less ▲]

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See detailNear-Death Experiences in patients with locked-in syndrome
Charland-Verville, Vanessa ULg; Lugo Ramirez, Zulay del Rosario ULg; Jourdan, Jean-Pierre et al

Poster (2014, October 04)

Near-Death Experiences (NDEs) are classically associated with positive emotions like peacefulness, happiness and joy [1-3]. To date, few negative NDEs reports have been documented [4]. Although NDEs ... [more ▼]

Near-Death Experiences (NDEs) are classically associated with positive emotions like peacefulness, happiness and joy [1-3]. To date, few negative NDEs reports have been documented [4]. Although NDEs classically arise in the context of an acute severe brain damage, their associated memories are reported as being phenomenologically very rich and detailed [5]. To date, no satisfactory explanatory model exits to fully account for the rich phenomenology of NDEs following a severe acute brain injury [6]. Neurobiological hypotheses include cerebral hypoxia [7, 8] and temporal lobe dysfunctions [9] to account for some of the features occurring during NDEs. However, it has been recently shown that anoxic/hypoxic, traumatic and other supratentorial brain lesions do not seem to influence the content of a NDE when assessed with a standardized tool (i.e., Greyson NDE scale; [1]). Due to their particular brain lesion (i.e., pontine brainstem), locked-in syndrome (LIS) patients provide a unique opportunity to further investigate the neural correlates of NDEs. We here aimed at retrospectively characterizing the content of NDEs in patients with LIS having suffered from an acute brainstem lesion (cerebrovascular accident (CVA) or trauma; i.e., “LIS NDEs”) and to compare these experiences to those collected in a cohort of matched NDE experiencers after coma with supratentorial lesions (CVA or trauma; i.e., “classical NDEs”). [less ▲]

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See detailSwallowing in disorders of consciousness
Bicego, Aminata; Lejoly, Kelly ULg; Maudoux, Audrey et al

in Revue Neurologique (2014), 170(10),

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See detailNeurophysiology of hypnosis
VANHAUDENHUYSE, Audrey ULg; Laureys, Steven ULg; Faymonville, Marie-Elisabeth ULg

in Clinical Neurophysiology (2014), 44

We here review behavioral, neuroimaging and electrophysiological studies of hypnosis as a state, as well as hypnosis as a tool to modulate brain responses to painful stimulations. Studies have shown that ... [more ▼]

We here review behavioral, neuroimaging and electrophysiological studies of hypnosis as a state, as well as hypnosis as a tool to modulate brain responses to painful stimulations. Studies have shown that hypnotic processes modify internal (self awareness) as well as external (environmental awareness) brain networks. Brain mechanisms underlying the modulation of pain perception under hypnotic conditions involve cortical as well as subcortical areas including anterior cingulate and prefrontal cortices, basal ganglia and thalami. Combined with local anesthesia and conscious sedation in patients undergoing surgery, hypnosis is associated with improved peri- and postoperative comfort of patients and surgeons. Finally, hypnosis can be considered as a useful analogue for simulating conversion and dissociation symptoms in healthy subjects, permitting better characterization of these challenging disorders by producing clinically similar experiences. [less ▲]

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See detailNear-death experiences in non-life-threatening events and coma of different etiologies.
Charland-Verville, Vanessa ULg; Jourdan, Jean-Pierre; Thonnard, Marie ULg et al

Poster (2014, September 16)

Near death experiences (NDEs) are increasingly being reported as a clearly identifiable physiological and psychological reality of clinical significance. Empirical studies of NDEs have mostly been ... [more ▼]

Near death experiences (NDEs) are increasingly being reported as a clearly identifiable physiological and psychological reality of clinical significance. Empirical studies of NDEs have mostly been conducted in patients with life threatening situations such as cardiac arrest [1-5] or (albeit more rarely) in patients with severe traumatic brain injury[6]. To the best of our knowledge, no study has formally compared the influence of the cause of coma to the intensity or content of the NDE. Using the Greyson NDE scale [7], the present retrospective study aimed at: (1) exploring the NDE intensity and content in “NDE-like” accounts following non-life-threatening events versus “real NDE” following coma; (2) comparing the “real NDE” characteristics according to the etiology of the brain damage (anoxic, traumatic or other) and; (3) comparing our retrospectively obtained data in anoxic coma to historical previously published prospectively collected post-anoxic NDEs. [less ▲]

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See detailTranscranial magnetic stimulation combined with high density EEG in altered states of consciousness
Napolitani, M.; Bodart, Olivier ULg; Canali, P. et al

in Brain injury : [BI] (2014), 28(9), 1180-1189

Background: This review discusses the advantages of transcranial magnetic stimulation combined with high-density electroencephalography (TMS-hdEEG) over other current techniques of brain imaging. Methods ... [more ▼]

Background: This review discusses the advantages of transcranial magnetic stimulation combined with high-density electroencephalography (TMS-hdEEG) over other current techniques of brain imaging. Methods and results: Its application was reviewed, focusing particularly on disorders of consciousness, in the perspective of recent theories of consciousness. Assessment of non-communicative patients with disorders of consciousness remains a clinical challenge and objective measures of the level of consciousness are still needed. Current theories suggest that a key requirement for consciousness is the brain’s capacity to rapidly integrate information across different specialized cortical areas. TMS-EEG allows the stimulation of any given cortical area and the recording of the immediate electrical cortical response. This technique has recently been successfully employed to measure changes in brain complexity under physiological, pharmacological and pathological conditions. Conclusions: This suggests that TMS-EEG is a reliable tool to discriminate between conscious and unconscious patients at the single subject level. Future works are needed to validate and implement this technique as a clinical tool. [less ▲]

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See detailMeasuring consciousness in coma and related states
Di Perri, Carol; Thibaut, Aurore ULg; Soddu, Andrea ULg et al

in World Journal of Radiology (2014), 6(8),

Consciousness is a prismatic and ambiguous concept that still eludes any universal definition. Severe acquired brain injuries resulting in a disorder of consciousness (DOC) provide a model from which ... [more ▼]

Consciousness is a prismatic and ambiguous concept that still eludes any universal definition. Severe acquired brain injuries resulting in a disorder of consciousness (DOC) provide a model from which insights into consciousness can be drawn. A number of recent studies highlight the difficulty in making a diagnosis in patients with DOC based only on behavioral assessments. Here we aim to provide an overview of how neuroimaging techniques can help assess patients with DOC. Such techniques are expected to facilitate a more accurate understanding of brain function in states of unconsciousness and to improve the evaluation of the patient’s cognitive abilities by providing both diagnostic and prognostic indicators. [less ▲]

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See detailDetecting awareness in patients with disorders of consciousness using a hybrid brain–computer interface
Pan, Jiahui; Xie, Qiuyou; He, Yanbin et al

in Journal of Neural Engineering (2014)

Objective. The bedside detection of potential awareness in patients with disorders of consciousness (DOC) currently relies only on behavioral observations and tests; however, the misdiagnosis rates in ... [more ▼]

Objective. The bedside detection of potential awareness in patients with disorders of consciousness (DOC) currently relies only on behavioral observations and tests; however, the misdiagnosis rates in this patient group are historically relatively high. In this study, we proposed a visual hybrid brain–computer interface (BCI) combining P300 and steady-state evoked potential (SSVEP) responses to detect awareness in severely brain injured patients. Approach. Four healthy subjects, seven DOC patients who were in a vegetative state (VS, n = 4) or minimally conscious state (MCS, n = 3), and one locked-in syndrome (LIS) patient attempted a command-following experiment. In each experimental trial, two photos were presented to each patient; one was the patientʼs own photo, and the other photo was unfamiliar. The patients were instructed to focus on their own or the unfamiliar photos. The BCI system determined which photo the patient focused on with both P300 and SSVEP detections. Main results. Four healthy subjects, one of the 4 VS, one of the 3 MCS, and the LIS patient were able to selectively attend to their own or the unfamiliar photos (classification accuracy, 66–100%). Two additional patients (one VS and one MCS) failed to attend the unfamiliar photo (50–52%) but achieved significant accuracies for their own photo (64–68%). All other patients failed to show any significant response to commands (46–55%). Significance. Through the hybrid BCI system, command following was detected in four healthy subjects, two of 7 DOC patients, and one LIS patient. We suggest that the hybrid BCI system could be used as a supportive bedside tool to detect awareness in patients with DOC. [less ▲]

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See detailThe Glasgow Coma Scale: time for critical reappraisal?
Laureys, Steven ULg; Bodart, Olivier ULg; Gosseries, Olivia ULg

in Lancet Neurology (2014), Vol 13

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See detailHow Does Your Formulation of Lesion-Induced States of Diminished Consciousness Fit with AIM? Do You Suppose That Brain Stem Damage Affects Activation (A) and Modulation (M)?
Charland-Verville, Vanessa ULg; Laureys, Steven ULg

in J. Allan Hobson, Nicholas Tranquillo (Ed.) Dream Consciousness: A New Approach to the Brain and Its Mind (2014)

Allan Hobson’s AIM model (Hobson, 1998) is build according to three main dimensions. The first component, Activation, describes brain’s activation processes and is closely linked to the level of ... [more ▼]

Allan Hobson’s AIM model (Hobson, 1998) is build according to three main dimensions. The first component, Activation, describes brain’s activation processes and is closely linked to the level of consciousness. According to the model, the brain is highly active in wakefulness and REM sleep but will show much less activity during NREM sleep. The second component, Input/output gateway, controls the inhibition of external stimuli. When slowly falling asleep, the gateway shuts down and inhibits the external stimuli; the brain is no longer involved in processing external perceptions. Then the brain starts its oniric phase and the focus switches to internal inputs. Finally, the third dimension, Modulation, refers to the different ways of cognitive processing (executive functions), judgment, volition and memory. According to the model, those cognitive processes are lacking in REM sleep (i.e., the brain cannot keep a record of its conscious experience during dreaming as opposed to waking state) because of the changes between the aminergic system (norepinephrine and serotonin; dominant in waking but ineffective in REM sleep) and the cholinergic system (acetylcholine; unfettered in REM sleep). These three dimensions maintain a dynamic and reciprocal interaction over the sleep-wake cycle’s variations (wakefulness, NREM and REM sleep) and each of them can be expressed with lower or higher intensities depending on the level of consciousness. [less ▲]

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See detailThe vegetative state/unresponsive wakefulness syndrome: a systematic review of prevalence studies
Van Erp, WS; Lavrijsen, JC; Van De Laar, FA et al

in European Journal of Neurology (2014)

One of the worst outcomes of acquired brain injury is the vegetative state, recently renamed ‘unresponsive wakefulness syndrome’ (VS/UWS). A patient in VS/UWS shows reflexive behaviour such as spontaneous ... [more ▼]

One of the worst outcomes of acquired brain injury is the vegetative state, recently renamed ‘unresponsive wakefulness syndrome’ (VS/UWS). A patient in VS/UWS shows reflexive behaviour such as spontaneous eye opening and breathing, but no signs of awareness of the self or the environment. We performed a systematic review of VS/UWS prevalence studies and assessed their reliability. Medline, Embase, the Cochrane Library, CINAHL and PsycINFO were searched in April 2013 for cross-sectional point or period prevalence studies explicitly stating the prevalence of VS/UWS due to acute causes within the general population. We additionally checked bibliographies and consulted experts in the field to obtain ‘grey data’ like government reports. Relevant publications underwent quality assessment and data-extraction. We retrieved 1032 papers out of which 14 met the inclusion criteria. Prevalence figures varied from 0.2 to 6.1 VS/UWS patients per 100 000 members of the population. However, the publications’ methodological quality differed substantially, in particular with regards to inclusion criteria and diagnosis verification. The reliability of VS/UWS prevalence figures is poor. Methodological flaws in available prevalence studies, the fact that 5/14 of the studies predate the identification of the minimally conscious state (MCS) as a distinct entity in 2002, and insufficient verification of included cases may lead to both overestimation and underestimation of the actual number of patients in VS/UWS. [less ▲]

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See detailPosterior Cingulate Cortex-Related Co-Activation Patterns: A Resting State fMRI Study in Propofol-Induced Loss of Consciousness
Amico, Enrico ULg; Gomez, Francisco; Di Perri, Carol et al

in PLoS ONE (2014), 9

Background: Recent studies have been shown that functional connectivity of cerebral areas is not a static phenomenon, but exhibits spontaneous fluctuations over time. There is evidence that fluctuating ... [more ▼]

Background: Recent studies have been shown that functional connectivity of cerebral areas is not a static phenomenon, but exhibits spontaneous fluctuations over time. There is evidence that fluctuating connectivity is an intrinsic phenomenon of brain dynamics that persists during anesthesia. Lately, point process analysis applied on functional data has revealed that much of the information regarding brain connectivity is contained in a fraction of critical time points of a resting state dataset. In the present study we want to extend this methodology for the investigation of resting state fMRI spatial pattern changes during propofol-induced modulation of consciousness, with the aim of extracting new insights on brain networks consciousness-dependent fluctuations. Methods: Resting-state fMRI volumes on 18 healthy subjects were acquired in four clinical states during propofol injection: wakefulness, sedation, unconsciousness, and recovery. The dataset was reduced to a spatio-temporal point process by selecting time points in the Posterior Cingulate Cortex (PCC) at which the signal is higher than a given threshold (i.e., BOLD intensity above 1 standard deviation). Spatial clustering on the PCC time frames extracted was then performed (number of clusters = 8), to obtain 8 different PCC co-activation patterns (CAPs) for each level of consciousness. Results: The current analysis shows that the core of the PCC-CAPs throughout consciousness modulation seems to be preserved. Nonetheless, this methodology enables to differentiate region-specific propofol-induced reductions in PCC-CAPs, some of them already present in the functional connectivity literature (e.g., disconnections of the prefrontal cortex, thalamus, auditory cortex), some others new (e.g., reduced co-activation in motor cortex and visual area). Conclusion: In conclusion, our results indicate that the employed methodology can help in improving and refining the characterization of local functional changes in the brain associated to propofol-induced modulation of consciousness. [less ▲]

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See detailVolitional electromyographic responses in disorders of consciousness
Habbal, Dina; Gosseries, Olivia ULg; Noirhomme, Quentin ULg et al

in Brain Injury (2014)

The aim of the study was to validate the use of electromyography (EMG) for detecting responses to command in patients in vegetative state/unresponsive wakefulness syndrome (VS/UWS) or in minimally ... [more ▼]

The aim of the study was to validate the use of electromyography (EMG) for detecting responses to command in patients in vegetative state/unresponsive wakefulness syndrome (VS/UWS) or in minimally conscious state (MCS). Methods: Thirty-eight patients were included in the study (23 traumatic, 25 patients >1 year post-onset), 10 diagnosed as being in VS/UWS, eight in MCS- (no response to command) and 20 in MCS+ (response to command). Eighteen age-matched controls participated in the experiment. The paradigm consisted of three commands (i.e. 'Move your hands', 'Move your legs' and 'Clench your teeth') and one control sentence (i.e. 'It is a sunny day') presented in random order. Each auditory stimulus was repeated 4-times within one block with a stimulus-onset asynchrony of 30 seconds. Results: Post-hoc analyses with Bonferroni correction revealed that EMG activity was higher solely for the target command in one patient in permanent VS/UWS and in three patients in MCS+. Conclusion: The use of EMG could help clinicians to detect conscious patients who do not show any volitional response during standard behavioural assessments. However, further investigations should determine the sensitivity of EMG as compared to neuroimaging and electrophysiological assessments. [less ▲]

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See detailNear-death experiences in non-life-threatening events and coma of different etiologies.
Charland-Verville, Vanessa ULg; Jourdan, Jean-Pierre; Thonnard, Marie ULg et al

in Frontiers in human neuroscience (2014), 8(203),

BACKGROUND: Near death experiences (NDEs) are increasingly being reported as a clearly identifiable physiological and psychological reality of clinical significance. However, the definition and causes of ... [more ▼]

BACKGROUND: Near death experiences (NDEs) are increasingly being reported as a clearly identifiable physiological and psychological reality of clinical significance. However, the definition and causes of the phenomenon as well as the identification of NDE experiencers is still a matter of debate. To date, the most widely used standardized tool to identify and characterize NDEs in research is the Greyson NDE scale. Using this scale, retrospective and prospective studies have been trying to estimate their incidence in various populations but few studies have attempted to associate the experiences' intensity and content to etiology. METHODS: This retrospective investigation assessed the intensity and the most frequently recounted features of self-reported NDEs after a non-life-threatening event (i.e., "NDE-like" experience) or after a pathological coma (i.e., "real NDE") and according to the etiology of the acute brain insult. We also compared our retrospectively acquired data in anoxic coma with historical data from the published literature on prospective post-anoxic studies using the Greyson NDE scale. RESULTS: From our 190 reports who met the criteria for NDE (i.e., Greyson NDE scale total score >7/32), intensity (i.e., Greyson NDE scale total score) and content (i.e., Greyson NDE scale features) did not differ between "NDE-like" (n = 50) and "real NDE" (n = 140) groups, nor within the "real NDE" group depending on the cause of coma (anoxic/traumatic/other). The most frequently reported feature was peacefulness (89-93%). Only 2 patients (1%) recounted a negative experience. The overall NDE core features' frequencies were higher in our retrospective anoxic cohort when compared to historical published prospective data. CONCLUSIONS: It appears that "real NDEs" after coma of different etiologies are similar to "NDE-like" experiences occurring after non-life threatening events. Subjects reporting NDEs retrospectively tend to have experienced a different content compared to the prospective experiencers. [less ▲]

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See detailAn independent SSVEP-based brain-computer interface in locked-in-syndrome
Lesenfants, Damien ULg; Habbal, Dina; Lugo et al

in Journal of Neural Engineering (2014)

OBJECTIVE: Steady-state visually evoked potential (SSVEP)-based brain-computer interfaces (BCIs) allow healthy subjects to communicate. However, their dependence on gaze control prevents their use with ... [more ▼]

OBJECTIVE: Steady-state visually evoked potential (SSVEP)-based brain-computer interfaces (BCIs) allow healthy subjects to communicate. However, their dependence on gaze control prevents their use with severely disabled patients. Gaze-independent SSVEP-BCIs have been designed but have shown a drop in accuracy and have not been tested in brain-injured patients. In the present paper, we propose a novel independent SSVEP-BCI based on covert attention with an improved classification rate. We study the influence of feature extraction algorithms and the number of harmonics. Finally, we test online communication on healthy volunteers and patients with locked-in syndrome (LIS). APPROACH: Twenty-four healthy subjects and six LIS patients participated in this study. An independent covert two-class SSVEP paradigm was used with a newly developed portable light emitting diode-based 'interlaced squares' stimulation pattern. MAIN RESULTS: Mean offline and online accuracies on healthy subjects were respectively 85 ± 2% and 74 ± 13%, with eight out of twelve subjects succeeding to communicate efficiently with 80 ± 9% accuracy. Two out of six LIS patients reached an offline accuracy above the chance level, illustrating a response to a command. One out of four LIS patients could communicate online. SIGNIFICANCE: We have demonstrated the feasibility of online communication with a covert SSVEP paradigm that is truly independent of all neuromuscular functions. The potential clinical use of the presented BCI system as a diagnostic (i.e., detecting command-following) and communication tool for severely brain-injured patients will need to be further explored. [less ▲]

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See detailUnresponsive wakefulness & translational neurorehabilitation.
Charland-Verville, Vanessa ULg; Thibaut, Aurore ULg; Wannez, Sarah ULg et al

Scientific conference (2014, April 10)

The past 15years have provided an unprecedented collection of discoveries that bear upon our scientific understanding of recovery of consciousness in the human brain following severe brain damage ... [more ▼]

The past 15years have provided an unprecedented collection of discoveries that bear upon our scientific understanding of recovery of consciousness in the human brain following severe brain damage. Highlighted among these discoveries are unique demonstrations that patients with little or no behavioral evidence of conscious awareness may retain critical cognitive capacities and the first scientific demonstrations that some patients, with severely injured brains and very longstanding conditions of limited behavioral responsiveness, may nonetheless harbor latent capacities for recovery. Included among such capacities are particularly human functions of language and higher-level cognition that either spontaneously or through direct interventions may reemerge even at long time intervals or remain unrecognized. When patients in “persistent vegetative state” (recently also coined unresponsive wakefulness syndrome) show minimal signs of consciousness but are unable to reliably communicate the term minimally responsive or minimally conscious state (MCS) is used. MCS was recently subcategorized based on the complexity of patients' behaviors: MCS+ describes high-level behavioral responses (i.e., command following, intelligible verbalizations or non-functional communication) and MCS- describes low-level behavioral responses (i.e., visual pursuit, localization of noxious stimulation or contingent behavior such as appropriate smiling or crying to emotional stimuli). Patients who show non-behavioral evidence of consciousness or communication only measurable via ancillary testing (i.e., functional MRI, positron emission tomography, EEG or evoked potentials) can be considered to be in a functional locked-in syndrome. An improved assessment of brain function in coma and related states is not only changing nosology and medical care but also offers a better-documented diagnosis and prognosis and helps to further identify the neural correlates of human consciousness. Taken together, recent studies show that awareness is an emergent property of the collective behavior of frontoparietal top-down connectivity. Within this network, external (sensory) awareness depends on lateral prefrontal/parietal cortices while internal (self) awareness correlates with precuneal/mesiofrontal midline activity. Of clinical importance, this knowledge now permits to improve the diagnosis, prognosis and treatment of patients with disorders of consciousness, which currently remains very challenging. New technological advances now also permit to show command-specific changes in fMRI, EEG or eye-pupil measurements providing motor-independent evidence of conscious thoughts and in come cases even of communication. We will conclude by discussing related ethical issues and the challenge of improving our clinical care and quality of life in these challenging patients with disorders of consciousness. [less ▲]

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See detailBiased binomial assessment of cross-validated estimation of classification accuracies illustrated in diagnosis predictions
Noirhomme, Quentin ULg; Lesenfants, Damien ULg; Gomez, Francisco et al

in NeuroImage: Clinical (2014), 4

Multivariate classification is used in neuroimaging studies to infer brain activation or in medical applications to infer diagnosis. Their results are often assessed through either a binomial or a ... [more ▼]

Multivariate classification is used in neuroimaging studies to infer brain activation or in medical applications to infer diagnosis. Their results are often assessed through either a binomial or a permutation test. Here, we simulated classification results of generated random data to assess the influence of the cross-validation scheme on the significance of results. Distributions built from classification of random data with crossvalidation did not follow the binomial distribution. The binomial test is therefore not adapted. On the contrary, the permutation test was unaffected by the cross-validation scheme. The influence of the crossvalidation was further illustrated on real-data from a brain–computer interface experiment in patients with disorders of consciousness and from an fMRI study on patients with Parkinson disease. Three out of 16 patients with disorders of consciousness had significant accuracy on binomial testing, but only one showed significant accuracy using permutation testing. In the fMRI experiment, the mental imagery of gait could discriminate significantly between idiopathic Parkinson’s disease patients and healthy subjects according to the permutation test but not according to the binomial test. Hence, binomial testing could lead to biased estimation of significance and false positive or negative results. In our view, permutation testing is thus recommended for clinical application of classification with cross-validation. [less ▲]

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