The neural correlates of conscious awareness revealed by the study of coma and related states
Conference (2012)Detailed reference viewed: 16 (0 ULg)
How to detect consciousness in severely brain injured patients?
Conference (2012)Detailed reference viewed: 15 (0 ULg)
Does the self-referential stimuli percpetion decrease with diminished level of consciousness?
in Vanhaudenhuyse, Audrey; BOVEROUX, Pierre; Bruno, Marie-Aurélie (Eds.) et al Journal of Neurology (2012)Detailed reference viewed: 27 (0 ULg)
Auditory resting-state network connectivity in tinnitus: a functional MRI study.
; Lefèbvre, Philippe ; et al
in PLoS ONE (2012), 7(5), 36222
The underlying functional neuroanatomy of tinnitus remains poorly understood. Few studies have focused on functional cerebral connectivity changes in tinnitus patients. The aim of this study was to test ... [more ▼]
The underlying functional neuroanatomy of tinnitus remains poorly understood. Few studies have focused on functional cerebral connectivity changes in tinnitus patients. The aim of this study was to test if functional MRI "resting-state" connectivity patterns in auditory network differ between tinnitus patients and normal controls. Thirteen chronic tinnitus subjects and fifteen age-matched healthy controls were studied on a 3 tesla MRI. Connectivity was investigated using independent component analysis and an automated component selection approach taking into account the spatial and temporal properties of each component. Connectivity in extra-auditory regions such as brainstem, basal ganglia/NAc, cerebellum, parahippocampal, right prefrontal, parietal, and sensorimotor areas was found to be increased in tinnitus subjects. The right primary auditory cortex, left prefrontal, left fusiform gyrus, and bilateral occipital regions showed a decreased connectivity in tinnitus. These results show that there is a modification of cortical and subcortical functional connectivity in tinnitus encompassing attentional, mnemonic, and emotional networks. Our data corroborate the hypothesized implication of non-auditory regions in tinnitus physiopathology and suggest that various regions of the brain seem involved in the persistent awareness of the phenomenon as well as in the development of the associated distress leading to disabling chronic tinnitus. [less ▲]Detailed reference viewed: 21 (0 ULg)
Reduction in inter-hemispheric connectivity in disorders of consciousness.
; ; Soddu, Andrea et al
in PLoS ONE (2012), 7(5), 37238
Clinical diagnosis of disorders of consciousness (DOC) caused by brain injury poses great challenges since patients are often behaviorally unresponsive. A promising new approach towards objective DOC ... [more ▼]
Clinical diagnosis of disorders of consciousness (DOC) caused by brain injury poses great challenges since patients are often behaviorally unresponsive. A promising new approach towards objective DOC diagnosis may be offered by the analysis of ultra-slow (<0.1 Hz) spontaneous brain activity fluctuations measured with functional magnetic resonance imaging (fMRI) during the resting-state. Previous work has shown reduced functional connectivity within the "default network", a subset of regions known to be deactivated during engaging tasks, which correlated with the degree of consciousness impairment. However, it remains unclear whether the breakdown of connectivity is restricted to the "default network", and to what degree changes in functional connectivity can be observed at the single subject level. Here, we analyzed resting-state inter-hemispheric connectivity in three homotopic regions of interest, which could reliably be identified based on distinct anatomical landmarks, and were part of the "Extrinsic" (externally oriented, task positive) network (pre- and postcentral gyrus, and intraparietal sulcus). Resting-state fMRI data were acquired for a group of 11 healthy subjects and 8 DOC patients. At the group level, our results indicate decreased inter-hemispheric functional connectivity in subjects with impaired awareness as compared to subjects with intact awareness. Individual connectivity scores significantly correlated with the degree of consciousness. Furthermore, a single-case statistic indicated a significant deviation from the healthy sample in 5/8 patients. Importantly, of the three patients whose connectivity indices were comparable to the healthy sample, one was diagnosed as locked-in. Taken together, our results further highlight the clinical potential of resting-state connectivity analysis and might guide the way towards a connectivity measure complementing existing DOC diagnosis. [less ▲]Detailed reference viewed: 29 (2 ULg)
A role for the default mode network in the bases of disorders of consciousness.
; Soddu, Andrea ; et al
in Annals of Neurology (2012), 72(3), 335-43
OBJECTIVE: Functional connectivity in the default mode network (DMN) is known to be reduced in patients with disorders of consciousness, to a different extent depending on their clinical severity ... [more ▼]
OBJECTIVE: Functional connectivity in the default mode network (DMN) is known to be reduced in patients with disorders of consciousness, to a different extent depending on their clinical severity. Nevertheless, the integrity of the structural architecture supporting this network and its relation with the exhibited functional disconnections are very poorly understood. We investigated the structural connectivity and white matter integrity of the DMN in patients with disorders of consciousness of varying clinical severity. METHODS: Fifty-two patients--19 in a vegetative state (VS), 27 in a minimally conscious state (MCS), and 6 emerging from a minimally conscious state (EMCS)--and 23 healthy volunteers participated in the study. Structural connectivity was assessed by means of probabilistic tractography, and the integrity of the resulting fibers was characterized by their mean fractional anisotropy values. RESULTS: Patients showed significant impairments in all of the pathways connecting cortical regions within this network, as well as the pathway connecting the posterior cingulate cortex/precuneus with the thalamus, relative to the healthy volunteers. Moreover, the structural integrity of this pathway, as well as that of those connecting the posterior areas of the network, was correlated with the patients' behavioral signs for awareness, being higher in EMCS patients than those in the upper and lower ranges of the MCS patients, and lowest in VS patients. INTERPRETATION: These results provide a possible neural substrate for the functional disconnection previously described in these patients, and reinforce the importance of the DMN in the genesis of awareness and the neural bases of its disorders. [less ▲]Detailed reference viewed: 24 (2 ULg)
Functional neuroanatomy underlying the clinical subcategorization of minimally conscious state patients.
Bruno, Marie-Aurélie ; Majerus, Steve ; Boly, Mélanie et al
in Journal of Neurology (2012), 259(6), 1087-98
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 ... [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 (fronto-temporo-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 interpreted as evidence of residual sensory consciousness. MCS+ patients showed preserved metabolism and functional connectivity in language networks arguably reflecting some additional higher order or extended consciousness albeit devoid of clinical verbal or nonverbal expression. [less ▲]Detailed reference viewed: 220 (10 ULg)
Burnout in healthcare workers managing chronic patients with disorders of consciousness.
Gosseries, Olivia ; Demertzi, Athina ; et al
in Brain Injury (2012)
Objectives: The aim of this study was to assess the presence of burnout among professional caregivers managing patients with severe brain injury recovering from coma and working in neurorehabilitation ... [more ▼]
Objectives: The aim of this study was to assess the presence of burnout among professional caregivers managing patients with severe brain injury recovering from coma and working in neurorehabilitation centres or nursing homes. Methods: The Maslach Burnout Inventory was sent to 40 centres involved in the Belgian federal network for the care of vegetative and minimally conscious patients. The following demographic data were also collected: age, gender, profession, expertise in the field, amount of time spent with patients and working place. Results: Out of 1068 questionnaires sent, 568 were collected (53% response rate). Forty-five were excluded due to missing data. From the 523 healthcare workers, 18% (n = 93) presented a burnout, 33% (n = 171) showed emotional exhaustion and 36% (n = 186) had a depersonalization. Profession (i.e. nurse/nursing assistants), working place (i.e. nursing home) and the amount of time spent with patients were associated with burnout. The logistic regression showed that profession was nevertheless the strongest variable linked to burnout. Conclusions: According to this study, a significant percentage of professional caregivers and particularly nurses taking care of patients in a vegetative state and in a minimally conscious state suffered from burnout. Prevention of burnout symptoms among caregivers is crucial and is expected to promote more efficient medical care of these challenging patients. [less ▲]Detailed reference viewed: 39 (5 ULg)
Feasibility of oral feeding in patients with disorders of consciousness
Maudoux, Audrey ; BREUSKIN, Ingrid ; Gosseries, Olivia et al
in Schnakers, Caroline; Laureys, Steven (Eds.) Coma and Disorders of Consciousness (2012)Detailed reference viewed: 33 (7 ULg)
Désordres de la conscience : aspects éthiques.
Demertzi, Athina ; Gosseries, Olivia ; Bruno, Marie-Aurélie et al
in Schnakers, Caroline; LAUREYS, Steven (Eds.) Comas et états de conscience altérée (2011)
L’apparition de la ventilation mécanique dans les années cinquante et le développement des soins intensifs dans les années soixante ont permis à de nombreux patients de survivre à de graves lésions ... [more ▼]
L’apparition de la ventilation mécanique dans les années cinquante et le développement des soins intensifs dans les années soixante ont permis à de nombreux patients de survivre à de graves lésions cérébrales. Bien que ces avancées technologiques soient étonnantes, de nombreux patients vont alors se retrouver dans des états cliniques critiques peu rencontrés auparavant (1). L’impact éthique de ces états d’inconscience se reflète lors de la rédaction des premiers comités de bioéthique et lors de l’apparition du concept d’acharnement thérapeutique. En 1968, le comité spécial de l’école médicale de Harvard a publié un article essentiel redéfinissant la mort comme étant un coma irréversible et une perte permanente de toutes les fonctions cérébrales (2). Le comité, composé de dix médecins, d’un théologien, d’un avocat et d’un historien des sciences, a débattu des questions médicales, juridiques et sociétales quant à la prise en charge des patients en mort cérébrale. Nous donnerons ici un bref aperçu des principales questions éthiques liées à la notion de conscience et à la prise en charge médicale des patients atteints de troubles de la conscience (TDC) tels que le coma, l’état végétatif et l’état de conscience minimale. Nous mettrons également l’accent sur le problème de la gestion de la douleur et des prises de décision en fin de vie. [less ▲]Detailed reference viewed: 85 (17 ULg)
Hypnotic modulation of resting state fMRI default mode and extrinsic network connectivity
Demertzi, Athina ; Soddu, Andrea ; FAYMONVILLE, Marie-Elisabeth et al
in Progress in Brain Research (2011), 193
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 ... [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 network showed an increased connectivity in bilateral angular and middle frontal gyri, whereas its posterior midline and parahippocampal structures decreased their connectivity during hypnosis, supposedly related to an altered “self” awareness and posthypnotic amnesia. In our view, fMRI resting state studies of physiological (e.g., sleep or hypnosis), pharmacological (e.g., sedation or anesthesia), and pathological modulation (e.g., coma or related states) of “intrinsic” default mode and anticorrelated “extrinsic” sensory networks, and their interaction with other cerebral networks, will further improve our understanding of the neural correlates of subjective awareness. [less ▲]Detailed reference viewed: 119 (22 ULg)
Automated EEG entropy measurements in coma, vegetative state/unresponsive wakefulness syndrome and minimally conscious state
Gosseries, Olivia ; Schnakers, Caroline ; LEDOUX, Didier et al
in Functional Neurology (2011)
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 ... [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 with Coma Recovery Scale total scores (r=0.49). Mean EEG entropy values were higher in minimally conscious (73±19; mean and standard deviation) than in vegetative/unresponsive wakefulness syndrome patients (45±28). Receiver operating characteristic analysis revealed an entropy cut-off value of 52 differentiating acute unconscious from minimally conscious patients (sensitivity 89% and specificity 90%). In chronic patients, entropy measurements offered no reliable diagnostic information. EEG entropy measurements did not allow prediction of outcome. User-independent time-frequency balanced spectral EEG entropy measurements seem to constitute an interesting diagnostic – albeit not prognostic – tool for assessing neural network complexity in disorders of consciousness in the acute setting. Future studies are needed before using this tool in routine clinical practice, and these should seek to improve automated EEG quantification paradigms in order to reduce the remaining false negative and false positive findings. [less ▲]Detailed reference viewed: 284 (11 ULg)
Neural plasticity lessons from disorders of consciousness
Demertzi, Athina ; Schnakers, Caroline ; Soddu, Andrea et al
in Frontiers in Psychology (2011), 1
Communication and intentional behavior are supported by the brain?s integrity at a structural and a functional level. When widespread loss of cerebral connectivity is brought about as a result of a severe ... [more ▼]
Communication and intentional behavior are supported by the brain?s integrity at a structural and a functional level. When widespread loss of cerebral connectivity is brought about as a result of a severe brain injury, in many cases patients are not capable of conscious interactive behavior and are said to suffer from disorders of consciousness (e.g., coma, vegetative state /unresponsive wakefulness syndrome, minimally conscious states). This lesion paradigm has offered not only clinical insights, as how to improve diagnosis, prognosis and treatment, but also put forward scientific opportunities to study the brain?s plastic abilities. We here review interventional and observational studies performed in severely brain-injured patients with regards to recovery of consciousness. The study of the recovered conscious brain (spontaneous and/or after surgical or pharmacologic interventions), suggests a link between some specific brain areas and the capacity of the brain to sustain conscious experience, challenging at the same time the notion of fixed temporal boundaries in rehabilitative processes. Altered functional connectivity, cerebral structural reorganization as well as behavioral amelioration after invasive treatments will be discussed as the main indices for plasticity in these challenging patients. The study of patients with chronic disorders of consciousness may, thus, provide further insights not only at a clinical level (i.e., medical management and rehabilitation) but also from a scientific-theoretical perspective (i.e., the brain?s plastic abilities and the pursuit of the neural correlate of consciousness). [less ▲]Detailed reference viewed: 76 (3 ULg)
Resting state activity in patients with disorders of consciousness.
Soddu, Andrea ; Vanhaudenhuyse, Audrey ; et al
in Functional Neurology (2011), 26(1), 37-43
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 ... [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 needed before fMRI resting state data can be used as proper biomarkers in severe brain injury. However, we anticipate that such developments will boost clinical resting state fMRI studies, allowing for easy and fast acquisitions and ultimately improve the diagnosis and prognosis in the absence of DOC patients' active collaboration in data acquisition. [less ▲]Detailed reference viewed: 51 (16 ULg)
Changes in fMRI resting state activity during propofol-induced unconsciousness.
; Guldenmund, Justus Pieter ; Demertzi, Athina et al
Poster (2011)Detailed reference viewed: 12 (2 ULg)
Resting state brain connectivity during Propofol sedation and recovery in healthy subjects: implications for sedation of patients with disorders of consciousness.
Guldenmund, Justus Pieter ; Boveroux, Pierre ; et al
Poster (2011)Detailed reference viewed: 15 (2 ULg)
Brain functional integration decreases during propofol-induced loss of consciousness.
Schrouff, Jessica ; ; Boly, Mélanie et al
in NeuroImage (2011), 57(1), 198-205
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 ... [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 was particularly affected between parietal areas and frontal or temporal regions during deep sedation. Our findings suggest that the breakdown in brain integration is the neural correlate of the loss of consciousness induced by propofol. They stress the important role played by parietal and frontal areas in the generation of consciousness. [less ▲]Detailed reference viewed: 89 (34 ULg)