Papers by Audrey Vanhaudenhuyse
Advances in Consciousness Research, 2015
The past 15 years have provided an unprecedented collection of discoveries that bear upon our sci... more The past 15 years have provided an unprecedented collection of discoveries that bear upon our scientific understanding of 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. 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. This chapter provides an overview of the scientific study of coma and related states at the macroscopic systems level.
Functional neurology
Zolpidem has been reported as an "awakening drug" in some patients with disorders of co... 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-b...
Progress in brain research, 2011
Resting state fMRI (functional magnetic resonance imaging) acquisitions are characterized by low-... more Resting state fMRI (functional magnetic resonance imaging) acquisitions are characterized by low-frequency spontaneous activity in a default mode network (encompassing medial brain areas and linked to self-related processes) and an anticorrelated "extrinsic" system (encompassing lateral frontoparietal areas and modulated via external sensory stimulation). In order to better determine the functional contribution of these networks to conscious awareness, we here sought to transiently modulate their relationship by means of hypnosis. We used independent component analysis (ICA) on resting state fMRI acquisitions during normal wakefulness, under hypnotic state, and during a control condition of autobiographical mental imagery. As compared to mental imagery, hypnosis-induced modulation of resting state fMRI networks resulted in a reduced "extrinsic" lateral frontoparietal cortical connectivity, possibly reflecting a decreased sensory awareness. The default mode networ...
Functional neurology
Recent advances in the study of spontaneous brain activity have demonstrated activity patterns th... more Recent advances in the study of spontaneous brain activity have demonstrated activity patterns that emerge with no task performance or sensory stimulation; these discoveries hold promise for the study of higher-order associative network functionality. Additionally, such advances are argued to be relevant in pathological states, such as disorders of consciousness (DOC), i.e., coma, vegetative and minimally conscious states. Recent studies on resting state activity in DOC, measured with functional magnetic resonance imaging (fMRI) techniques, show that functional connectivity is disrupted in the task-negative or the default mode network. However, the two main approaches employed in the analysis of resting state functional connectivity data (i.e., hypothesis-driven seed-voxel and data-driven independent component analysis) present multiple methodological difficulties, especially in non-collaborative DOC patients. Improvements in motion artifact removal and spatial normalization are nee...
Functional neurology
Monitoring the level of consciousness in brain-injured patients with disorders of consciousness i... more Monitoring the level of consciousness in brain-injured patients with disorders of consciousness is crucial as it provides diagnostic and prognostic information. Behavioral assessment remains the gold standard for assessing consciousness but previous studies have shown a high rate of misdiagnosis. This study aimed to investigate the usefulness of electroencephalography (EEG) entropy measurements in differentiating unconscious (coma or vegetative) from minimally conscious patients. Left fronto-temporal EEG recordings (10-minute resting state epochs) were prospectively obtained in 56 patients and 16 age-matched healthy volunteers. Patients were assessed in the acute (≤1 month post-injury; n=29) or chronic (>1 month post-injury; n=27) stage. The etiology was traumatic in 23 patients. Automated online EEG entropy calculations (providing an arbitrary value ranging from 0 to 91) were compared with behavioral assessments (Coma Recovery Scale-Revised) and outcome. EEG entropy correlated w...
Revue médicale de Liège, 2009
Traumatic and non-traumatic brain injured disorders of consciousness patients are still challengi... more Traumatic and non-traumatic brain injured disorders of consciousness patients are still challenging for diagnosis, prognosis, ethical and socio-economic reasons. Currently, there remains a high rate of misdiagnosis of the vegetative state (Schnakers, et al. 2009). Recent advances in MRI techniques (diffusion tensor, magnetic resonance spectroscopy and functional imaging) provide data that could improve the diagnostic and prognostic evaluation and management of these patients.
Sleep, 2014
Memory reactivation appears to be a fundamental process in memory consolidation. In this study we... more Memory reactivation appears to be a fundamental process in memory consolidation. In this study we tested the influence of memory reactivation during rapid eye movement (REM) sleep on memory performance and brain responses at retrieval in healthy human participants. Participants: Fifty-six healthy subjects (28 women and 28 men, age [mean ± standard deviation]: 21.6 ± 2.2 y) participated in this functional magnetic resonance imaging (fMRI) study. Methods and Results: Auditory cues were associated with pictures of faces during their encoding. These memory cues delivered during REM sleep enhanced subsequent accurate recollections but also false recognitions. These results suggest that reactivated memories interacted with semantically related representations, and induced new creative associations, which subsequently reduced the distinction between new and previously encoded exemplars. Cues had no effect if presented during stage 2 sleep, or if they were not associated with faces during encoding. Functional magnetic resonance imaging revealed that following exposure to conditioned cues during REM sleep, responses to faces during retrieval were enhanced both in a visual area and in a cortical region of multisensory (auditory-visual) convergence. Conclusions: These results show that reactivating memories during REM sleep enhances cortical responses during retrieval, suggesting the integration of recent memories within cortical circuits, favoring the generalization and schematization of the information.
PLoS ONE, 2014
Background: Recent studies have been shown that functional connectivity of cerebral areas is not ... 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. 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. 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). 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.
Coma and Disorders of Consciousness, 2012
ABSTRACT Eating and drinking are basic pleasures of life, considered as obvious to most of us. Ho... more ABSTRACT Eating and drinking are basic pleasures of life, considered as obvious to most of us. However, the ease with which we perform these actions masks the complexity of the underlying neuronal control. According to several studies, the frequency of dysphagia among subjects with severe brain injury is frequent. Faced with the difficult management of patients with an altered state of consciousness, the use of gustatory stimuli, as well as the rehabilitation of swallowing could constitute a supplementary therapy which is currently rarely considered. This review aims to summarize our current knowledge regarding the neural control of swallowing, to assess the role of awareness and willingness on the control of swallowing and, finally, to establish the feasibility of oral feeding in patients with disorders of consciousness.
médecine/sciences, 2011
L'état végétatif (EV), l'état de conscience minimale (ECM) et le locked-in syndrome (LIS) sont au... more L'état végétatif (EV), l'état de conscience minimale (ECM) et le locked-in syndrome (LIS) sont autant d'états qui peuvent succéder à un coma. Ces états se distinguent par le niveau de conscience et d'éveil qui leur est associé. L'éveil correspond au niveau de vigilance soustendu par les systèmes sous-corticaux du tronc cérébral, le mésencéphale et le thalamus. Alors que la conscience, ou le contenu conscient, est associée au cortex cérébral et à ses connexions sous corticales [1, 2]. Le coma est un état limité dans le temps dont la durée n'excède généralement pas deux à quatre semaines. Un patient dans le coma peut évoluer soit vers la mort cérébrale, soit vers un EV [3], soit vers une récupération de conscience rapide (Figure 1). Le coma est caractérisé par une absence totale d'éveil, même lors de stimulations intenses, et résulte d'une atteinte globale du cortex ou de la matière blanche, ou d'une lésion thalamique bilatérale avec préservation de la substance réticulée [4]. Les patients EV sont éveillés mais ne présentent aucun signe comportemental de conscience de soi ou de l'environnement [5]. Chez ces patients, les manifestations des fonctions motrices, auditives et visuelles sont restreintes à des réponses réflexes, et les réponses émotionnelles ne sont pas adaptées au contexte. Ces
The Neurology of Consciousness, 2009
Thirty years ago a stroke left me in a coma. When I awoke I found myself completely paralyzed and... more Thirty years ago a stroke left me in a coma. When I awoke I found myself completely paralyzed and unable to speak … I didn't know what paralysis was until I could move nothing but my eyes. I didn't know what loneliness was until I had to wait all night in the dark, in pain from head to foot, vainly hoping for someone to come with a teardrop of comfort. I didn't know what silence was until the only sound I could make was that of my own breath issuing from a hole drilled into my throat ' [1].
PLoS ONE, 2013
Since the dawn of time, Near-Death Experiences (NDEs) have intrigued and, nowadays, are still not... more Since the dawn of time, Near-Death Experiences (NDEs) have intrigued and, nowadays, are still not fully explained. Since reports of NDEs are proposed to be imagined events, and since memories of imagined events have, on average, fewer phenomenological characteristics than real events memories, we here compared phenomenological characteristics of NDEs reports with memories of imagined and real events. We included three groups of coma survivors (8 patients with NDE as defined by the Greyson NDE scale, 6 patients without NDE but with memories of their coma, 7 patients without memories of their coma) and a group of 18 age-matched healthy volunteers. Five types of memories were assessed using Memory Characteristics Questionnaire (MCQ -Johnson et al., 1988): target memories (NDE for NDE memory group, coma memory for coma memory group, and first childhood memory for no memory and control groups), old and recent real event memories and old and recent imagined event memories. Since NDEs are known to have high emotional content, participants were requested to choose the most emotionally salient memories for both real and imagined recent and old event memories. Results showed that, in NDE memories group, NDE memories have more characteristics than memories of imagined and real events (p,0.02). NDE memories contain more self-referential and emotional information and have better clarity than memories of coma (all ps,0.02). The present study showed that NDE memories contained more characteristics than real event memories and coma memories. Thus, this suggests that they cannot be considered as imagined event memories. On the contrary, their physiological origins could lead them to be really perceived although not lived in the reality. Further work is needed to better understand this phenomenon.
Neuroradiology, 2009
Following coma, some patients will recover wakefulness without signs of consciousness (only showi... more Following coma, some patients will recover wakefulness without signs of consciousness (only showing reflex movements, i.e., the vegetative state) or may show non-reflex movements but remain without functional communication (i.e., the minimally conscious state). Currently, there remains a high rate of misdiagnosis of the vegetative state (Schnakers et. al. BMC Neurol, 9:35, and the clinical and electrophysiological markers of outcome from the vegetative and minimally conscious states remain unsatisfactory. This should incite clinicians to use multimodal assessment to detect objective signs of consciousness and validate para-clinical prognostic markers in these challenging patients. This review will focus on advanced magnetic resonance imaging (MRI) techniques such as magnetic resonance spectroscopy, diffusion tensor imaging, and functional MRI (fMRI studies in both "activation" and "resting state" conditions) that were recently introduced in the assessment of patients with chronic disorders of consciousness.
NeuroImage, 2011
The vegetative state is a devastating condition where patients awaken from their coma (i.e., open... more The vegetative state is a devastating condition where patients awaken from their coma (i.e., open their eyes) but fail to show any behavioural sign of conscious awareness. Locked-in syndrome patients also awaken from their coma and are unable to show any motor response to command (except for small eye movements or blinks) but recover full conscious awareness of self and environment. Bedside evaluation of residual cognitive function in coma survivors often is difficult because motor responses may be very limited or inconsistent. We here aimed to disentangle vegetative from "locked-in" patients by an automatic procedure based on machine learning using fluorodeoxyglucose PET data obtained in 37 healthy controls and in 13 patients in a vegetative state. Next, the trained machine was tested on brain scans obtained in 8 patients with locked-in syndrome. We used a sparse probabilistic Bayesian learning framework called "relevance vector machine" (RVM) to classify the scans. The trained RVM classifier, applied on an input scan, returns a probability value (p-value) of being in one class or the other, here being "conscious" or not. Training on the control and vegetative state groups was assessed with a leave-one-out cross-validation procedure, leading to 100% classification accuracy. When applied on the locked-in patients, all scans were classified as "conscious" with a mean p-value of .95 (min .85). In conclusion, even with this relatively limited data set, we could train a classifier distinguishing between normal consciousness (i.e., wakeful conscious awareness) and the vegetative state (i.e., wakeful unawareness). Cross-validation also indicated that the clinical classification and the one predicted by the automatic RVM classifier were in accordance. Moreover, when applied on a third group of "locked-in" consciously aware patients, they all had a strong probability of being similar to the normal controls, as expected. Therefore, RVM classification of cerebral metabolic images obtained in coma survivors could become a useful tool for the automated PET-based diagnosis of altered states of consciousness.
Journal of Neurology, 2011
Patients in a minimally conscious state (MCS) show restricted signs of awareness but are unable t... more Patients in a minimally conscious state (MCS) show restricted signs of awareness but are unable to communicate. We assessed cerebral glucose metabolism in MCS patients and tested the hypothesis that this entity can be subcategorized into MCS-(i.e., patients only showing nonreflex behavior such as visual pursuit, localization of noxious stimulation and/or contingent behavior) and MCS? (i.e., patients showing command following). Patterns of cerebral glucose metabolism were studied using [ 18 F]-fluorodeoxyglucose-PET in 39 healthy volunteers (aged 46 ± 18 years) and 27 MCS patients of whom 13 were MCS-(aged 49 ± 19 years; 4 traumatic; 21 ± 23 months post injury) and 14 MCS? (aged 43 ± 19 years; 5 traumatic; 19 ± 26 months post injury). Results were thresholded for significance at false discovery rate corrected p \ 0.05. We observed a metabolic impairment in a bilateral subcortical (thalamus and caudate) and cortical (frontotemporo-parietal) network in nontraumatic and traumatic MCS patients. Compared to MCS-, patients in MCS? showed higher cerebral metabolism in left-sided cortical areas encompassing the language network, premotor, presupplementary motor, and sensorimotor cortices. A functional connectivity study showed that Broca's region was disconnected from the rest of the language network, mesiofrontal and cerebellar areas in MCS-as compared to MCS? patients. The proposed subcategorization of MCS based on the presence or absence of command following showed a different functional neuroanatomy. MCS-is characterized by preserved right hemispheric cortical metabolism M.
NeuroImage, 2011
Consciousness has been related to the amount of integrated information that the brain is able to ... more Consciousness has been related to the amount of integrated information that the brain is able to generate. In this paper, we tested the hypothesis that the loss of consciousness caused by propofol anesthesia is associated with a significant reduction in the capacity of the brain to integrate information. To assess the functional structure of the whole brain, functional integration and partial correlations were computed from fMRI data acquired from 18 healthy volunteers during resting wakefulness and propofol-induced deep sedation. Total integration was significantly reduced from wakefulness to deep sedation in the whole brain as well as within and between its constituent networks (or systems). Integration was systematically reduced within each system (i.e., brain or networks), as well as between networks. However, the ventral attentional network maintained interactions with most other networks during deep sedation. Partial correlations further suggested that functional connectivity ...
Human Brain Mapping, 2011
Objectives:Recent fMRI studies have shown that it is possible to reliably identify the default‐mo... more Objectives:Recent fMRI studies have shown that it is possible to reliably identify the default‐mode network (DMN) in the absence of any task, by resting‐state connectivity analyses in healthy volunteers. We here aimed to identify the DMN in the challenging patient population of disorders of consciousness encountered following coma. Experimental design: A spatial independent component analysis‐based methodology permitted DMN assessment, decomposing connectivity in all its different sources either neuronal or artifactual. Three different selection criteria were introduced assessing anticorrelation‐corrected connectivity with or without an automatic masking procedure and calculating connectivity scores encompassing both spatial and temporal properties. These three methods were validated on 10 healthy controls and applied to an independent group of 8 healthy controls and 11 severely brain‐damaged patients [locked‐in syndrome (n = 2), minimally conscious (n = 1), and vegetative state (n ...
Expert Review of Neurotherapeutics, 2008
Consciousness is here defined as a first-person experience that consists of two major components:... more Consciousness is here defined as a first-person experience that consists of two major components: arousal and awareness (Figure ) [1]. Arousal refers to the level of alertness and is supported by the function of the subcortical arousal systems in the brainstem, midbrain and thalamus [2]. Clinically, it is indicated by opening of the eyes. Awareness refers to the content of consciousness, and it is thought to be supported by the functional integrity of the cerebral cortex and its subcortical connections. Awareness can be further reduced to awareness of environment and of self [3]. Clinically, awareness of environment is assessed by evaluating command following and observing nonreflex motor behavior, such as eye tracking and localized responses to pain. Awareness of self, clinically a more ill-defined concept, can be assessed by the patients' response to autoreferential stimuli, such as the patients' own face in the mirror. An illustrative example of the relationship between the two components of consciousness is the transition from full wakefulness to deep sleep: the less aroused we get, the less aware we become of our surroundings. This review focuses on clinical methods and research techniques that are currently employed for assessing residual consciousness in coma survivors. The disorders of consciousness (DOC) are described below. The concept of brain death, as death based on neurological criteria, has been widely accepted worldwide [4]. Irreversible coma and absence of brain stem reflexes are the major clinical criteria that are followed by most US hospitals, but these criteria are apparently not practised in the same way by all institutions [5]. This implies that brain death may be determined in various ways, a fact that may have consequences in after death practices, such as organ transplantation [6]. In 1995, the American Academy of Neurology published the diagnostic guidelines for brain death [7], which are: Demonstration of coma; • Evidence for the cause of coma; • Absence of confounding factors, including • hypothermia, drugs, electrolyte and endocrine disturbances;
Clinical EEG and Neuroscience, 2014
Major clinical endpoints of general anesthesia, such as the alteration of consciousness, are achi... more Major clinical endpoints of general anesthesia, such as the alteration of consciousness, are achieved through effects of anesthetic agents on the central nervous system, and, more precisely, on the brain. Historically, clinicians and researchers have always been interested in quantifying and characterizing those effects through recordings of surface brain electrical activity, namely electroencephalography (EEG). Over decades of research, the complex signal has been dissected to extract its core substance, with significant advances in the interpretation of the information it may contain. Methodological, engineering, statistical, mathematical, and computer progress now furnishes advanced tools that not only allow quantification of the effects of anesthesia, but also shed light on some aspects of anesthetic mechanisms. In this article, we will review how advanced EEG serves the anesthesiologist in that respect, but will not review other intraoperative utilities that have no direct rela...
Brain Injury, 2008
The aim of the present study was to explore the concurrent validity, inter-rater agreement and di... more The aim of the present study was to explore the concurrent validity, inter-rater agreement and diagnostic sensitivity of a French adaptation of the Coma Recovery Scale-Revised (CRS-R) as compared to other coma scales such as the Glasgow Coma Scale (GCS), the Full Outline of UnResponsiveness scale (FOUR) and the Wessex Head Injury Matrix (WHIM). Research design: Multi-centric prospective study. Method and procedures: To test concurrent validity and diagnostic sensitivity, the four behavioural scales were administered in a randomized order in 77 vegetative and minimally conscious patients. Twenty-four clinicians with different professional backgrounds, levels of expertise and CRS-R experience were recruited to assess inter-rater agreement. Main outcomes and results: Good concurrent validity was obtained between the CRS-R and the three other standardized behavioural scales. Inter-rater reliability for the CRS-R total score and sub-scores was good, indicating that the scale yields reproducible findings across examiners and does not appear to be systematically biased by profession, level of expertise or CRS-R experience. Finally, the CRS-R demonstrated a significantly higher sensitivity to detect MCS patients, as compared to the GCS, the FOUR and the WHIM. The results show that the French version of the CRS-R is a valid and sensitive scale which can be used in severely brain damaged patients by all members of the medical staff.
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Papers by Audrey Vanhaudenhuyse