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See detailA European survey on attitudes towards pain and end-of-life issues in locked-in syndrome
Demertzi, Athina ULg; Jox, Ralf J; Racine, Eric et al

in Brain Injury (in press)

Objectives: Patients with locked-in syndrome often self-report a higher quality of life than generally expected. This study reports third-person attitudes towards several salient issues on locked-in ... [more ▼]

Objectives: Patients with locked-in syndrome often self-report a higher quality of life than generally expected. This study reports third-person attitudes towards several salient issues on locked-in syndrome. Methods: Close-ended survey among conference attendees from 33 European countries. Analysis included chi-square tests and logistic regressions. Results: From the 3332 respondents (33% physicians, 18% other clinicians, 49% other professions; 47% religious), 90% agreed that patients with locked-in syndrome can feel pain. The majority (75%) disagreed with treatment withdrawal, but 56% did not wish to be kept alive if they imagined themselves in this condition (p50.001). Religious and southern Europeans opposed to treatment withdrawal more often than non-religious (p50.001) and participants from the North (p¼0.001). When the locked-in syndrome was compared to disorders of consciousness, more respondents endorsed that being in a chronic locked-in syndrome was worse than being in a vegetative state or minimally conscious state for patients (59%) than they thought for families (40%, p50.001). Conclusions: Personal characteristics mediate opinions about locked-in syndrome. The dissociation between personal preferences and general opinions underlie the difference in perspective in disability. Ethical responses to dilemmas involving patients with locked-in syndrome should consider the diverging ethical attitudes of stakeholders. [less ▲]

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See detailImaging the Central Nervous System
Bodart, Olivier ULg; Laureys, Steven ULg

in Webb, A.; Angus, D.; Finfer, S. (Eds.) et al Oxford Textbook of Critical Care, Second Edition (in press)

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See detailDisorders of Consciousness
Bodart, Olivier ULg; Thibaut, Aurore ULg; Laureys, Steven ULg et al

in Citerio, G.; Smith, M.; Kofke, A. (Eds.) Oxford Textbook of neurocritical care (in press)

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See detailBrain stimulation for patients with disorders of consciousness
Thibaut, Aurore ULg; BODART, Olivier ULg; Laureys, Steven ULg

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

There is a long history of brain stimulation in medical science, and it was tested for years to try to treat several neurological diseases. Research has long been focused on some cortical areas and deep ... [more ▼]

There is a long history of brain stimulation in medical science, and it was tested for years to try to treat several neurological diseases. Research has long been focused on some cortical areas and deep brain structures like the prefrontal cortex and the thalamus. On the other hand, the treatment choices for patients with severe brain injury resulting in disorders of consciousness are still limited and research in this field remains challenging. In the current literature, only a few techniques of brain stimulation were studied scientifically in this population of patients. We will here describe noninvasive techniques, namely transcranial magnetic stimulation and transcranial direct current stimulation, which permit to stimulate the brain through the scalp. Next, we will discuss the current status of deep brain stimulation as treatment for patients with disorders of consciousness. Finally we will develop hypothesis to explain the mechanism of action of these means of brain stimulation. We will see that repetitive transcranial magnetic stimulation and transcranial direct current stimulation studies showed encouraging results, with improvements in the behavioral signs of consciousness of severely brain injured patients, both chronic and acute, traumatic or non-traumatic, without influence of the stimulation side. Deep brain stimulation showed more impressive and extensive behavioral improvement after the implantation of an electrical stimulator in the intralaminar nuclei. However, this procedure is riskier and the number of patients who can benefit from this intervention are still limited. These therapeutic approaches are still in their infancy. In the years to follow, interventions should multiply and therapeutic measures should be more accessible, controlled and effective. [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 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 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 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 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 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 detailImpact of Aphasia on Consciousness Assessment: A Cross-Sectional Study.
Schnakers, C; Bessou, H; Rubi-Fessen, I et al

in Neurorehabilitation & Neural Repair (2014)

BACKGROUND: . Previous findings suggest that language disorders may occur in severely brain-injured patients and could interfere with behavioral assessments of consciousness. However, no study ... [more ▼]

BACKGROUND: . Previous findings suggest that language disorders may occur in severely brain-injured patients and could interfere with behavioral assessments of consciousness. However, no study investigated to what extent language impairment could affect patients' behavioral responses. OBJECTIVE: . To estimate the impact of receptive and/or productive language impairments on consciousness assessment. METHODS: . Twenty-four acute and subacute stroke patients with different types of aphasia (global, n = 11; Broca, n = 4; Wernicke, n = 3; anomic, n = 4; mixed, n = 2) were recruited in neurology and neurosurgery units as well as in rehabilitation centers. The Coma Recovery Scale-Revised (CRS-R) was administered. RESULTS: . We observed that 25% (6 out of 24) of stroke patients with a diagnosis of aphasia and 54% (6 out of 11) of patients with a diagnosis of global aphasia did not reach the maximal CRS-R total score of 23. An underestimation of the consciousness level was observed in 3 patients with global aphasia who could have been misdiagnosed as being in a minimally conscious state, even in the absence of any documented period of coma. More precisely, lower subscores were observed on the communication, motor, oromotor, and arousal subscales. CONCLUSION: . Consciousness assessment may be complicated by the co-occurrence of severe language deficits. This stresses the importance of developing new tools or identifying items in existing scales, which may allow the detection of language impairment in severely brain-injured patients. [less ▲]

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See detailDiagnostic precision of PET imaging and functional MRI in disorders of consciousness: a clinical validation study
Stender, Johan; Gosseries, Olivia ULg; Bruno, Marie-Aurélie ULg et al

in Lancet Neurology (2014)

Background: Bedside clinical examinations can have high rates of misdiagnosis of unresponsive wakefulness syndrome (vegetative state) or minimally conscious state. The diagnostic and prognostic usefulness ... [more ▼]

Background: Bedside clinical examinations can have high rates of misdiagnosis of unresponsive wakefulness syndrome (vegetative state) or minimally conscious state. The diagnostic and prognostic usefulness of neuroimaging-based approaches has not been established in a clinical setting. We did a validation study of two neuroimaging-based diagnostic methods: PET imaging and functional MRI (fMRI). Methods: For this clinical validation study, we included patients referred to the University Hospital of Liège, Belgium, between January, 2008, and June, 2012, who were diagnosed by our unit with unresponsive wakefulness syndrome, locked-in syndrome, or minimally conscious state with traumatic or non-traumatic causes. We did repeated standardised clinical assessments with the Coma Recovery Scale—Revised (CRS—R), cerebral 18F-fluorodeoxyglucose (FDG) PET, and fMRI during mental activation tasks. We calculated the diagnostic accuracy of both imaging methods with CRS—R diagnosis as reference. We assessed outcome after 12 months with the Glasgow Outcome Scale—Extended. Findings: We included 41 patients with unresponsive wakefulness syndrome, four with locked-in syndrome, and 81 in a minimally conscious state (48=traumatic, 78=non-traumatic; 110=chronic, 16=subacute). 18F-FDG PET had high sensitivity for identification of patients in a minimally conscious state (93%, 95% CI 85—98) and high congruence (85%, 77—90) with behavioural CRS—R scores. The active fMRI method was less sensitive at diagnosis of a minimally conscious state (45%, 30—61) and had lower overall congruence with behavioural scores (63%, 51—73) than PET imaging. 18F-FDG PET correctly predicted outcome in 75 of 102 patients (74%, 64—81), and fMRI in 36 of 65 patients (56%, 43—67). 13 of 42 (32%) of the behaviourally unresponsive patients (ie, diagnosed as unresponsive with CRS—R) showed brain activity compatible with (minimal) consciousness (ie, activity associated with consciousness, but diminished compared with fully conscious individuals) on at least one neuroimaging test; 69% of these (9 of 13) patients subsequently recovered consciousness. Interpretation: Cerebral 18F-FDG PET could be used to complement bedside examinations and predict long-term recovery of patients with unresponsive wakefulness syndrome. Active fMRI might also be useful for differential diagnosis, but seems to be less accurate. Funding: The Belgian National Funds for Scientific Research (FNRS), Fonds Léon Fredericq, the European Commission, the James McDonnell Foundation, the Mind Science Foundation, the French Speaking Community Concerted Research Action, the University of Copenhagen, and the University of Liège. [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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