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See detailRegional cerebral metabolic patterns demonstrate the role of anterior forebrain mesocircuit dysfunction in the severely injured brain
Fridman, Esteban A; Beattie, Bradley J; Broft, Allegra et al

in Proceedings of the National Academy of Sciences of the United States of America (2014)

Although disorders of consciousness (DOCs) demonstrate widely varying clinical presentations and patterns of structural injury, global down-regulation and bilateral reductions in metabolism of the ... [more ▼]

Although disorders of consciousness (DOCs) demonstrate widely varying clinical presentations and patterns of structural injury, global down-regulation and bilateral reductions in metabolism of the thalamus and frontoparietal network are consistent findings. We test the hypothesis that global reductions of background synaptic activity in DOCs will associate with changes in the pattern of metabolic activity in the central thalamus and globus pallidus. We compared 32 [18F]fluorodeoxyglucose PETs obtained from severely brain-injured patients (BIs) and 10 normal volunteers (NVs). We defined components of the anterior forebrain mesocircuit on high-resolution T1-MRI (ventral, associative, and sensorimotor striatum; globus pallidus; central thalamus and noncentral thalamus). Metabolic profiles for BI and NV demonstrated distinct changes in the pattern of uptake: ventral and association striatum (but not sensorimotor) were significantly reduced relative to global mean uptake after BI; a relative increase in globus pallidus metabolism was evident in BI subjects who also showed a relative reduction of metabolism in the central thalamus. The reversal of globus pallidus and central thalamus profiles across BIs and NVs supports the mesocircuit hypothesis that broad functional (or anatomic) deafferentation may combine to reduce central thalamus activity and release globus pallidus activity in DOCs. In addition, BI subjects showed broad frontoparietal metabolic down-regulation consistent with prior studies supporting the link between central thalamic/pallidal metabolism and down-regulation of the frontoparietal network. Recovery of left hemisphere frontoparietal metabolic activity was further associated with command following. [less ▲]

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See detailWhite Matter Changes in Comatose Survivors of Anoxic Ischemic Encephalopathy and Traumatic Brain Injury: Comparative Diffusion-Tensor Imaging Study
Van Der Eerden, Anke; Khalilzadeh, Omid; Perlbarg, Vincent et al

in Radiology (2014), 270

Purpose:To analyze white matter pathologic abnormalities by using diffusion-tensor (DT) imaging in a multicenter prospective cohort of comatose patients following cardiac arrest or traumatic brain injury ... [more ▼]

Purpose:To analyze white matter pathologic abnormalities by using diffusion-tensor (DT) imaging in a multicenter prospective cohort of comatose patients following cardiac arrest or traumatic brain injury (TBI). Materials and Methods: Institutional review board approval and informed consent from proxies and control subjects were obtained. DT imaging was performed 5–57 days after insult in 49 cardiac arrest and 40 TBI patients. To control for DT imaging–processing variability, patients’ values were normalized to those of 111 control subjects. Automated segmentation software calculated normalized axial diffusivity (λ1) and radial diffusivity (λ) in 19 predefined white matter regions of interest (ROIs). DT imaging variables were compared by using general linear modeling, and side-to-side Pearson correlation coefficients were calculated. P values were corrected for multiple testing (Bonferroni). Results:In central white matter, λ1 differed from that in control subjects in six of seven TBI ROIs and five of seven cardiac arrest ROIs (all P < .01). The λ differed from that in control subjects in all ROIs in both patient groups (P < .01). In hemispheres, λ1 was decreased compared with that in control subjects in three of 12 TBI ROIs (P < .05) and nine of 12 cardiac arrest ROIs (P < .01). The λ was increased in all TBI ROIs (P < .01) and in seven of 12 cardiac arrest ROIs (P < .05). Cerebral hemisphere λ1 was lower in cardiac arrest than in TBI in six of 12 ROIs (P < .01), while λ was higher in TBI than in cardiac arrest in eight of 12 ROIs (P < .01). Diffusivity values were symmetrically distributed in cardiac arrest (P < .001 for side-to-side correlation) but not in TBI patients. Conclusion:DT imaging findings are consistent with the known predominance of cerebral hemisphere axonal injury in cardiac arrest and chiefly central myelin injury in TBI. This consistency supports the validity of DT imaging for differentiating axon and myelin damage in vivo in humans. [less ▲]

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See detailEffect of zolpidem in chronic disorders of consciousness: a prospective open-label study.
Thonnard, Marie ULg; Gosseries, Olivia ULg; Demertzi, Athina ULg et al

in Functional Neurology (2014)

Zolpidem has been reported as an "awakening drug" in some patients with disorders of consciousness (DOC). We here present the results of a prospective openlabel study in chronic DOC patients. Sixty ... [more ▼]

Zolpidem has been reported as an "awakening drug" in some patients with disorders of consciousness (DOC). We here present the results of a prospective openlabel study in chronic DOC patients. Sixty patients (35±15 years; 18 females; mean time since insult ± SD: 4±5.5 years; 31 with traumatic etiology) with a diagnosis of vegetative state/unresponsive wakefulness syndrome (n=28) or minimally conscious state (n=32) were behaviorally assessed using the Coma Recovery Scale-Revised (CRS-R) before and one hour after administration of 10 mg of zolpidem. At the group level, the diagnosis did not change after intake of zolpidem (p=0.10) and CRS-R total scores decreased (p=0.01). Twelve patients (20%) showed improved behaviors and/or CRS-R total scores after zolpidem administration but in only one patient was the diagnosis after zolpidem intake found to show a significant improvement (functional object use), which suggested a change of diagnosis. However, in this patient, a double-blind placebo-controlled trial was performed in order to better specify the effects of zolpidem, but the patient, on this trial, failed to show any clinical improvements. The present open-label study therefore failed to show any clinically significant improvement (i.e., change of Effect of zolpidem in chronic disorders of consciousness: a prospective open-label study diagnosis) in any of the 60 studied chronic DOC patients. [less ▲]

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See detailAssessing consciousness in coma and related states using transcranial magnetic stimulation combined with electroencephalography.
Gosseries, Olivia ULg; Thibaut, Aurore ULg; Boly, Mélanie ULg et al

in Annales Françaises d'Anesthésie et de Réanimation (2014)

Thanks to advances in medical care, an increased number of patients recover from coma. However, some remain in vegetative/unresponsive wakefulness syndrome or in a minimally conscious state. Detection of ... [more ▼]

Thanks to advances in medical care, an increased number of patients recover from coma. However, some remain in vegetative/unresponsive wakefulness syndrome or in a minimally conscious state. Detection of awareness in severely brain-injured patients is challenging because it relies on behavioral assessments, which can be affected by motor, sensory and cognitive impairments of the patients. Other means of evaluation are needed to improve the accuracy of the diagnosis in this challenging population. We will here review the different altered states of consciousness occurring after severe brain damage, and explain the difficulties associated with behavioral assessment of consciousness. We will then describe a non-invasive technique, transcranial magnetic stimulation combined with high-density electroencephalography (TMS-EEG), which has allowed us to detect the presence or absence of consciousness in different physiological, pathological and pharmacological states. Some potential underlying mechanisms of the loss of consciousness will then be discussed. In conclusion, TMS-EEG is highly promising in identifying markers of consciousness at the individual level and might be of great value for clinicians in the assessment of consciousness. [less ▲]

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See detailQuantifying cortical EEG responses to TMS in (un)consciousness
Sarasso, S; Rosanova, M; Casali, A.G et al

in Clinical EEG and Neuroscience : Official Journal of the EEG and Clinical Neuroscience Society (ENCS) (2014)

We normally assess another individual's level of consciousness based on her or his ability to interact with the surrounding environment and communicate. Usually, if we observe purposeful behavior ... [more ▼]

We normally assess another individual's level of consciousness based on her or his ability to interact with the surrounding environment and communicate. Usually, if we observe purposeful behavior, appropriate responses to sensory inputs, and, above all, appropriate answers to questions, we can be reasonably sure that the person is conscious. However, we know that consciousness can be entirely within the brain, even in the absence of any interaction with the external world; this happens almost every night, while we dream. Yet, to this day, we lack an objective, dependable measure of the level of consciousness that is independent of processing sensory inputs and producing appropriate motor outputs. Theoretically, consciousness is thought to require the joint presence of functional integration and functional differentiation, otherwise defined as brain complexity. Here we review a series of recent studies in which Transcranial Magnetic Stimulation combined with electroencephalography (TMS/EEG) has been employed to quantify brain complexity in wakefulness and during physiological (sleep), pharmacological (anesthesia) and pathological (brain injury) loss of consciousness. These studies invariably show that the complexity of the cortical response to TMS collapses when consciousness is lost during deep sleep, anesthesia and vegetative state following severe brain injury, while it recovers when consciousness resurges in wakefulness, during dreaming, in the minimally conscious state or locked-in syndrome. The present paper will also focus on how this approach may contribute to unveiling the pathophysiology of disorders of consciousness affecting brain-injured patients. Finally, we will underline some crucial methodological aspects concerning TMS/EEG measurements of brain complexity. [less ▲]

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See detailConsciousness and Unconsciousness: An EEG Perspective
Noirhomme, Quentin ULg; Laureys, Steven ULg

in Clinical EEG and Neuroscience (2014), 45

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See detailDIRECTED INFORMATION TRANSFER IN SCALP ELECTROENCEPHALOGRAPHIC RECORDINGS: INSIGHTS ON DISORDERS OF CONSCIOUSNESS
Marinazzo, Daniele; Gosseries, Olivia ULg; Boly, Mélanie ULg et al

in Clinical EEG and Neuroscience : Official Journal of the EEG and Clinical Neuroscience Society (ENCS) (2014)

Introduction: The neural mechanisms underlying electrophysiological changes observed in patients with disorders of consciousness following a coma remain poorly understood. The aim of this article is to ... [more ▼]

Introduction: The neural mechanisms underlying electrophysiological changes observed in patients with disorders of consciousness following a coma remain poorly understood. The aim of this article is to investigate the mechanisms underlying the differences in spontaneous electroencephalography between patients in vegetative/unresponsive wakefulness syndrome, minimally conscious state, emergence of the minimally conscious state and age-matched healthy control subjects. <br />Methods: Forty recording of spontaneous scalp electroencephalography were performed in 27 patients who were comatose on admission, and on healthy controls. Multivariate Granger Causality and Transfer Entropy were applied on the data. <br />Results: Distinctive patterns of putative bottlenecks of information were associated to each conscious state. Healthy controls are characterized by a greater amount of synergetic contributions from duplets of variables. <br />Conclusion: A novel set of measures was tested to get a novel insight on the pattern of information transfer in a network of scalp electrodes in patients with disorders of consciousness. [less ▲]

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See detailAutomated analysis of background EEG and reactivity during therapeutic hypothermia in comatose patients after cardiac arrest
Noirhomme, Quentin ULg; Lehembre, Rémy; Lugo, Zulay et al

in Clinical EEG and Neuroscience : Official Journal of the EEG and Clinical Neuroscience Society (ENCS) (2014)

Visual analysis of electroencephalography (EEG) background and reactivity during therapeutic hypothermia provides important outcome information, but is time-consuming and not always consistent between ... [more ▼]

Visual analysis of electroencephalography (EEG) background and reactivity during therapeutic hypothermia provides important outcome information, but is time-consuming and not always consistent between reviewers. Automated EEG analysis may help quantify the brain damage. Forty-six comatose patients in therapeutic hypothermia, after cardiac arrest, were included in the study. EEG background was quantified with burst-suppression ratio (BSR) and approximate entropy, both used to monitor anesthesia. Reactivity was detected through change in the power spectrum of signal before and after stimulation. Automatic results obtained almost perfect agreement (discontinuity) to substantial agreement (background reactivity) with a visual score from EEG-certified neurologists. Burst-suppression ratio was more suited to distinguish continuous EEG background from burst-suppression than approximate entropy in this specific population. Automatic EEG background and reactivity measures were significantly related to good and poor outcome. We conclude that quantitative EEG measurements can provide promising information regarding current state of the patient and clinical outcome, but further work is needed before routine application in a clinical setting. [less ▲]

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See detailA vibrotactile P300-based BCI for consciousness detection and communication
Lugo, Zulay; Rodriguez, Javi; Lechner, Alexander et al

in Clinical EEG and Neuroscience : Official Journal of the EEG and Clinical Neuroscience Society (ENCS) (2014)

Brain–computer interface (BCI) has been used for many years for communication in severely disabled patients. BCI based on electrophysiological signals has enabled communication, using auditory or visual ... [more ▼]

Brain–computer interface (BCI) has been used for many years for communication in severely disabled patients. BCI based on electrophysiological signals has enabled communication, using auditory or visual stimuli to elicit event-related potentials (ERPs). The aim of this study was to determine whether patients with locked-in syndrome (LIS) could elicit a P300 wave, using a vibrotactile oddball paradigm for establishing somatosensory BCI-based communication. Six chronic LIS patients performed 2electroencephalography (EEG)-based vibrotactile P300 oddball tasks. After a simple mental counting task of the target stimuli, participants were instructed to answer 5 questions by counting the vibration on either the right wrist for “yes” or the left wrist for “no.” All participants were able to elicit a P300 wave using the vibrotactile oddball paradigm BCI task. In the counting task, 4 patients got accuracies of 100% (average above chance). In the communication task, one patient achieved 100% accuracy (average above chance). We have shown the feasibility of eliciting a P300 response using vibrotactile stimulation in patients with LIS. The present study provides evidence that this approach can be used for EEG-based BCI communications in this patient group. This is the first study to prove the feasibility of a BCI based on somatosensory (vibratory) stimulation in a group of braininjured patients. Furthermore, this approach could be used for the detection of consciousness in non-communicating patients due to severe brain injuries. [less ▲]

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

in Journal of Cerebral Blood Flow & Metabolism (2014)

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

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

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See detailPositron emission tomography imaging in altered states of consciousness: Coma, sleep and hypnosis
Thibaut, Aurore ULg; Chatelle, Camille ULg; Stender, Johan et al

in Dierckx, Rudi; Otte, Andreas; Vries, Erik (Eds.) et al PET and SPECT in Neurology (2014)

Positron emission tomography (PET) allows studies of cerebral metabolism and blood flow and has been widely used to investigate physiological mechanisms underlying altered states of consciousness. The aim ... [more ▼]

Positron emission tomography (PET) allows studies of cerebral metabolism and blood flow and has been widely used to investigate physiological mechanisms underlying altered states of consciousness. The aim of this chapter is to review the current literature on brain metabolism during physiological or pathological loss of consciousness including studies on disorders of consciousness arising from severe brain injury (vegetative/unresponsive or minimally conscious states), and related non-pathological conditions such as sleep and hypnotic states. Identifying brain areas specifically involved in conscious processing, these studies have contributed to our understanding of the underlying physiology of consciousness. The precuneal and cingulate cortices, for example, seem to be key areas for maintaining consciousness awareness. Other areas such as hypothalamus, amygdala or the temporo-occipital cortex seem to play a role in different states of unconsciousness such as rapid eye movement sleep and hypnosis. PET studies permit a better comprehension of the loss of consciousness, and focus the implication of specific neural areas and networks in pathologically (vegetative/unresponsive or minimally conscious states), physiologically (sleep), and hypnotically altered states of consciousness. [less ▲]

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See detailCerebral functional connectivity periodically (de)synchronizes with anatomical constraints
Liegeois, Raphaël ULg; Sepulchre, Rodolphe ULg; LAUREYS, Steven ULg

E-print/Working paper (2014)

This paper studies the link between resting-state functional connectivity (FC), measured by the correlations of the fMRI BOLD time courses, and structural connectivity (SC), estimated through fiber ... [more ▼]

This paper studies the link between resting-state functional connectivity (FC), measured by the correlations of the fMRI BOLD time courses, and structural connectivity (SC), estimated through fiber tractography. Instead of a static analysis based on the correlation between SC and the FC averaged over the entire fMRI time series, we propose a dynamic analysis, based on the time evolution of the correlation between SC and a suitably windowed FC. Assessing the statistical significance of the time series against random phase permutations, our data show a pronounced peak of significance for time window widths around 20-30 TR (40-60 sec). Using the appropriate window width, we show that FC patterns oscillate between phases of high modularity, primarily shaped by anatomy, and phases of low modularity, primarily shaped by inter-network connectivity. Building upon recent results in dynamic FC, this emphasizes the potential role of SC as a transitory architecture between different highly connected resting state FC patterns. Finally, we show that networks implied in consciousness-related processes, such as the default mode network (DMN), contribute more to these brain-level fluctuations compared to other networks, such as the motor or somatosensory networks. This suggests that the fluctuations between FC and SC are capturing mind-wandering effects. [less ▲]

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See detailMultiple fMRI system-level baseline connectivity is disrupted in patients with consciousness alterations
Demertzi, Athina ULg; Gomez, Francisco; Crone, Julia-Sophia et al

in Cortex : A Journal Devoted to the Study of the Nervous System & Behavior (2014), 52

Introduction: In healthy conditions, group-level fMRI resting state analyses identify ten resting state networks (RSNs) of cognitive relevance. Here, we aim to assess the tennetwork model in severely ... [more ▼]

Introduction: In healthy conditions, group-level fMRI resting state analyses identify ten resting state networks (RSNs) of cognitive relevance. Here, we aim to assess the tennetwork model in severely brain-injured patients suffering from disorders of consciousness and to identify those networks which will be most relevant to discriminate between patients and healthy subjects. Methods: 300 fMRI volumes were obtained in 27 healthy controls and 53 patients in minimally conscious state (MCS), vegetative state/unresponsive wakefulness syndrome (VS/ UWS) and coma. Independent component analysis (ICA) reduced data dimensionality. The ten networks were identified by means of a multiple template-matching procedure and were tested on neuronality properties (neuronal vs non-neuronal) in a data-driven way. Univariate analyses detected between-group differences in networks’ neuronal properties and estimated voxel-wise functional connectivity in the networks, which were significantly less identifiable in patients. A nearest-neighbor “clinical” classifier was used to determine the networks with high between-group discriminative accuracy. Results: Healthy controls were characterized by more neuronal components compared to patients in VS/UWS and in coma. Compared to healthy controls, fewer patients in MCS and VS/UWS showed components of neuronal origin for the left executive control network, default mode network (DMN), auditory, and right executive control network. The “clinical” classifier indicated the DMN and auditory network with the highest accuracy (85.3%) in discriminating patients from healthy subjects. [less ▲]

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See detailAssessment of Patient Comfort During Palliative Sedation: Is it always Reliable?
Deschepper, R; Bilsen, J; Laureys, Steven ULg

in Annual Update in Intensive Care and Emergency Medicine (2014)

"When death knocks at the door of our ward, we do not easily open the door”, an intensivist once said. In the intensive care unit (ICU) and emergency department, care is strongly focused on cure and ... [more ▼]

"When death knocks at the door of our ward, we do not easily open the door”, an intensivist once said. In the intensive care unit (ICU) and emergency department, care is strongly focused on cure and resuscitation. Notwithstanding the technological progress made in intensive and emergency medicine, a substantial number of the patients admitted to the ICU cannot be saved. In these cases, it is important to make a timely shift from curative efforts to palliative care, so that futile and burdensome interventions can be avoided. When death becomes imminent, a major concern of the family members and caregivers is to assure maximal comfort during the dying process. A central aspect of good end-of-life care is to keep the patient, as much as possible, free of pain and other kinds of distress. However, many critically ill patients often suffer from symptoms such as pain and delirium. More than 50 % of critically ill patients in the ICU experience moderate to severe pain and pain in critically ill patients often remains untreated [1]. [less ▲]

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See detailDisorders of consciousness after acquired brain injury: the state of the science
Giacino, Joseph T; Fins, Joseph J; Laureys, Steven ULg et al

in Nature Reviews Neurology (2014)

The concept of consciousness continues to defy definition and elude the grasp of philosophical and scientific efforts to formulate a testable construct that maps to human experience. Severe acquired brain ... [more ▼]

The concept of consciousness continues to defy definition and elude the grasp of philosophical and scientific efforts to formulate a testable construct that maps to human experience. Severe acquired brain injury results in the dissolution of consciousness, providing a natural model from which key insights about consciousness may be drawn. In the clinical setting, neurologists and neurorehabilitation specialists are called on to discern the level of consciousness in patients who are unable to communicate through word or gesture, and to project outcomes and recommend approaches to treatment. Standards of care are not available to guide clinical decision-making for this population, often leading to inconsistent, inaccurate and inappropriate care. In this Review, we describe the state of the science with regard to clinical management of patients with prolonged disorders of consciousness. We review consciousness-altering pathophysiological mechanisms, specific clinical syndromes, and novel diagnostic and prognostic applications of advanced neuroimaging and electrophysiological procedures. We conclude with a provocative discussion of bioethical and medicolegal issues that are unique to this population and have a profound impact on care, as well as raising questions of broad societal interest. [less ▲]

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See detailNeuroimaging in Disorders of Consciousness
Bodart, Olivier ULg; Charland-Verville, Vanessa ULg; Laureys, Steven ULg et al

in Filippi, M. (Ed.) Oxford Textbook of Clinical Neurology (2014)

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See detailAmantadine, Apomorphine and Zolpidem in the Treatment of Disorders of Consciousness
Gosseries, Olivia ULg; Charland-Verville, Vanessa ULg; Thonnard, Marie ULg et al

in Current Pharmaceutical Design (2014), 20

Survivors of severe brain injuries may end up in a state of 'wakeful unresponsiveness' or in a minimally conscious state. Pharmacological treatments of patients with disorders of consciousness aim to ... [more ▼]

Survivors of severe brain injuries may end up in a state of 'wakeful unresponsiveness' or in a minimally conscious state. Pharmacological treatments of patients with disorders of consciousness aim to improve arousal levels and recovery of consciousness. We here provide a systematic overview of the therapeutic effects of amantadine, apomorphine and zolpidem in patients recovering from coma. Evidence from clinical trials using these commonly prescribed pharmacological agents suggests positive changes in the neurological status in patients, leading sometimes to dramatic improvements. These findings are discussed in the context of current hypotheses of these agents' therapeutic mechanisms on cerebral function. In order to enhance our understanding of the underlying pathophysiological mechanisms of these drugs, we suggest combining sensitive and specific behavioral tools with neuroimaging and electrophysiological measures in large randomized, double-blind, placebo-controlled experimental designs. We conclude that the pharmacokinetics and pharmacodynamics of amantadine, apomorphine and zolpidem need further exploration to determine which treatment would provide a better neurological outcome regarding the patient's etiology, diagnosis, time since injury and overall condition. [less ▲]

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See detailOn the statistical assessment of small sample classification
Noirhomme, Quentin ULg; Lesenfants, Damien ULg; Gomez, Francisco et al

Conference (2013, December)

Classifiers start to be used in medical application to infer diagnosis. Their results are assessed through either a binomial or a permutation test. Distributions built from classification of random data ... [more ▼]

Classifiers start to be used in medical application to infer diagnosis. Their results are assessed through either a binomial or a permutation test. Distributions built from classification of random data with cross-validation, did not follow the theoretical binomial distribution, showing that binomial test was not conservative enough. A permutation test is thus recommended. [less ▲]

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See detailCommon resting brain dynamics indicate a possible mechanism underlying zolpidem response in severe brain injury
Williams, Shawniqua; Conte, Mary; Goldfine, Andrew et al

in eLife (2013)

Zolpidem produces paradoxical recovery of speech, cognitive and motor functions in select subjects with severe brain injury but underlying mechanisms remain unknown. In three diverse patients with known ... [more ▼]

Zolpidem produces paradoxical recovery of speech, cognitive and motor functions in select subjects with severe brain injury but underlying mechanisms remain unknown. In three diverse patients with known zolpidem responses we identify a distinctive pattern of EEG dynamics that suggests a mechanistic model. In the absence of zolpidem, all subjects show a strong low frequency oscillatory peak ∼6–10 Hz in the EEG power spectrum most prominent over frontocentral regions and with high coherence (∼0.7–0.8) within and between hemispheres. Zolpidem administration sharply reduces EEG power and coherence at these low frequencies. The ∼6–10 Hz activity is proposed to arise from intrinsic membrane properties of pyramidal neurons that are passively entrained across the cortex by locally-generated spontaneous activity. Activation by zolpidem is proposed to arise from a combination of initial direct drug effects on cortical, striatal, and thalamic populations and further activation of underactive brain regions induced by restoration of cognitively-mediated behaviors. [less ▲]

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