Resting state networks and consciousness: alterations of multiple resting state network connectivity in physiological, pharmacological, and pathological consciousness States.
Heine, Lizette ; Soddu, Andrea ; et al
in Frontiers in Psychology [=FPSYG] (2012), 3
In order to better understand the functional contribution of resting state activity to conscious cognition, we aimed to review increases and decreases in functional magnetic resonance imaging (fMRI ... [more ▼]
In order to better understand the functional contribution of resting state activity to conscious cognition, we aimed to review increases and decreases in functional magnetic resonance imaging (fMRI) functional connectivity under physiological (sleep), pharmacological (anesthesia), and pathological altered states of consciousness, such as brain death, coma, vegetative state/unresponsive wakefulness syndrome, and minimally conscious state. The reviewed resting state networks were the DMN, left and right executive control, salience, sensorimotor, auditory, and visual networks. We highlight some methodological issues concerning resting state analyses in severely injured brains mainly in terms of hypothesis-driven seed-based correlation analysis and data-driven independent components analysis approaches. Finally, we attempt to contextualize our discussion within theoretical frameworks of conscious processes. We think that this "lesion" approach allows us to better determine the necessary conditions under which normal conscious cognition takes place. At the clinical level, we acknowledge the technical merits of the resting state paradigm. Indeed, fast and easy acquisitions are preferable to activation paradigms in clinical populations. Finally, we emphasize the need to validate the diagnostic and prognostic value of fMRI resting state measurements in non-communicating brain damaged patients. [less ▲]Detailed reference viewed: 14 (1 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: 19 (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: 166 (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: 32 (3 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: 32 (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: 77 (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: 107 (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: 244 (11 ULg)
Neural plasticity lessons from disorders of consciousness
Demertzi, Athina ; Schnakers, Caroline ; Soddu, Andrea et al
in Frontiers in Psychology [=FPSYG] (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: 70 (3 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: 76 (33 ULg)
Imagerie fonctionnelle et états de conscience altérée
Vanhaudenhuyse, Audrey ; Boly, Mélanie ; Bruno, Marie-Aurélie et al
in Schnakers, Caroline; LAUREYS, Steven (Eds.) Coma et états de conscience altérée (2011)Detailed reference viewed: 14 (1 ULg)
Clinical and paraclinical diagnosis in altered states of consciousness
Scientific conference (2011)Detailed reference viewed: 9 (0 ULg)
Coma et état végétatif: aspects comportementaux, électrophysiologiques et techniques d'imagerie
Vanhaudenhuyse, Audrey ; Bruno, Marie-Aurélie
Conference (2011)Detailed reference viewed: 5 (0 ULg)
La neuro-imagerie: un outil diagnostique des etats de conscience alteree.
Thonnard, Marie ; Boly, Mélanie ; et al
in Medecine Sciences : M/S (2011), 27(1), 77-81
Vegetative and minimally conscious states diagnosis remained a major clinical challenge. New paradigms such as measurement of the global cerebral metabolism, the structural and functional integrity of ... [more ▼]
Vegetative and minimally conscious states diagnosis remained a major clinical challenge. New paradigms such as measurement of the global cerebral metabolism, the structural and functional integrity of fronto-parietal network, or the spontaneous activity in resting state have been shown to be helpful to disentangle vegetative from minimally conscious patients. Active neuroimagery paradigms also allow detecting voluntary and conscious activity in non-communicative patients. The implementation of these methods in clinical routine could permit to reduce the current high rate of misdiagnosis (40%). [less ▲]Detailed reference viewed: 15 (5 ULg)
From unresponsive wakefulness to minimally conscious PLUS and functional locked-in syndromes: recent advances in our understanding of disorders of consciousness.
Bruno, Marie-Aurélie ; Vanhaudenhuyse, Audrey ; Thibaut, Aurore et al
in Journal of Neurology (2011), 258(7), 1373-84
Functional neuroimaging and electrophysiology studies are changing our understanding of patients with coma and related states. Some severely brain damaged patients may show residual cortical processing in ... [more ▼]
Functional neuroimaging and electrophysiology studies are changing our understanding of patients with coma and related states. Some severely brain damaged patients may show residual cortical processing in the absence of behavioural signs of consciousness. Given these new findings, the diagnostic errors and their potential effects on treatment as well as concerns regarding the negative associations intrinsic to the term vegetative state, the European Task Force on Disorders of Consciousness has recently proposed the more neutral and descriptive term unresponsive wakefulness syndrome. When vegetative/unresponsive patients show minimal signs of consciousness but are unable to reliably communicate the term minimally responsive or minimally conscious state (MCS) is used. MCS was recently subcategorized based on the complexity of patients' behaviours: MCS+ describes high-level behavioural responses (i.e., command following, intelligible verbalizations or non-functional communication) and MCS- describes low-level behavioural responses (i.e., visual pursuit, localization of noxious stimulation or contingent behaviour such as appropriate smiling or crying to emotional stimuli). Finally, patients who show non-behavioural evidence of consciousness or communication only measurable via para-clinical testing (i.e., functional MRI, positron emission tomography, EEG or evoked potentials) can be considered to be in a functional locked-in syndrome. An improved assessment of brain function in coma and related states is not only changing nosology and medical care but also offers a better-documented diagnosis and prognosis and helps to further identify the neural correlates of human consciousness. [less ▲]Detailed reference viewed: 17 (3 ULg)
"Relevance vector machine" consciousness classifier applied to cerebral metabolism of vegetative and locked-in patients.
Phillips, Christophe ; Bruno, Marie-Aurélie ; Maquet, Pierre et al
in NeuroImage (2011), 56(2), 797808
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 ... [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. [less ▲]Detailed reference viewed: 40 (11 ULg)