Propofol induced unconsciousness: fMRI total neuronal activity and resting state networks.
; Guldenmund, Justus Pieter ; et al
Poster (2012)Detailed reference viewed: 28 (3 ULg)
Regional brain damage associated with reduced consciousness in patients with disorders of consciousness.
Guldenmund, Justus Pieter ; Soddu, Andrea ; VANHAUDENHUYSE, Audrey et al
Poster (2012)Detailed reference viewed: 16 (3 ULg)
Brain-computer interfacing in disorders of consciousness.
Chatelle, Camille ; ; Noirhomme, Quentin et al
in Brain Injury (2012), 26(12), 1510-22
Background: Recent neuroimaging research has strikingly demonstrated the existence of covert awareness in some patients with disorders of consciousness (DoC). These findings have highlighted the potential ... [more ▼]
Background: Recent neuroimaging research has strikingly demonstrated the existence of covert awareness in some patients with disorders of consciousness (DoC). These findings have highlighted the potential for the development of simple brain-computer interfaces (BCI) as a diagnosis in behaviourally unresponsive patients. Objectives: This study here reviews current EEG-based BCIs that hold potential for assessing and eventually assisting patients with DoC. It highlights key areas for further development that might eventually make their application feasible in this challenging patient group. Methods: The major types of BCIs proposed in the literature are considered, namely those based on the P3 potential, sensorimotor rhythms, steady state oscillations and slow cortical potentials. In each case, a brief overview of the relevant literature is provided and then their relative merits for BCI applications in DoC are considered. Results: A range of BCI designs have been proposed and tested for enabling communication in fully conscious, paralysed patients. Although many of these have potential applicability for patients with DoC, they share some key challenges that need to be overcome, including limitations of stimulation modality, feedback, user training and consistency. Conclusion: Future work will need to address the technical and practical challenges facing reliable implementation at the patient's bedside. [less ▲]Detailed reference viewed: 11 (0 ULg)
Neural correlates of consciousness during general anesthesia using functional magnetic resonance imaging (fMRI).
BONHOMME, Vincent ; ; Brichant, Jean-François et al
in Archives italiennes de biologie (2012), 150(2-3), 155-63
This paper reviews the current knowledge about the mechanisms of anesthesia-induced alteration of consciousness. It is now evident that hypnotic anesthetic agents have specific brain targets whose ... [more ▼]
This paper reviews the current knowledge about the mechanisms of anesthesia-induced alteration of consciousness. It is now evident that hypnotic anesthetic agents have specific brain targets whose function is hierarchically altered in a dose-dependent manner. Higher order networks, thought to be involved in mental content generation, as well as sub-cortical networks involved in thalamic activity regulation seems to be affected first by increasing concentrations of hypnotic agents that enhance inhibitory neurotransmission. Lower order sensory networks are preserved, including thalamo-cortical connectivity into those networks, even at concentrations that suppress responsiveness, but cross-modal sensory interactions are inhibited. Thalamo-cortical connectivity into the consciousness networks decreases with increasing concentrations of those agents, and is transformed into an anti-correlated activity between the thalamus and the cortex for the deepest levels of sedation, when the subject is non responsive. Future will tell us whether these brain function alterations are also observed with hypnotic agents that mainly inhibit excitatory neurotransmission. The link between the observations made using fMRI and the identified biochemical targets of hypnotic anesthetic agents still remains to be identified. [less ▲]Detailed reference viewed: 25 (2 ULg)
Connectivity changes underlying spectral EEG changes during propofol-induced loss of consciousness.
Boly, Mélanie ; ; et al
in The Journal of neuroscience : the official journal of the Society for Neuroscience (2012), 32(20), 7082-90
The mechanisms underlying anesthesia-induced loss of consciousness remain a matter of debate. Recent electrophysiological reports suggest that while initial propofol infusion provokes an increase in fast ... [more ▼]
The mechanisms underlying anesthesia-induced loss of consciousness remain a matter of debate. Recent electrophysiological reports suggest that while initial propofol infusion provokes an increase in fast rhythms (from beta to gamma range), slow activity (from delta to alpha range) rises selectively during loss of consciousness. Dynamic causal modeling was used to investigate the neural mechanisms mediating these changes in spectral power in humans. We analyzed source-reconstructed data from frontal and parietal cortices during normal wakefulness, propofol-induced mild sedation, and loss of consciousness. Bayesian model selection revealed that the best model for explaining spectral changes across the three states involved changes in corticothalamic interactions. Compared with wakefulness, mild sedation was accounted for by an increase in thalamic excitability, which did not further increase during loss of consciousness. In contrast, loss of consciousness per se was accompanied by a decrease in backward corticocortical connectivity from frontal to parietal cortices, while thalamocortical connectivity remained unchanged. These results emphasize the importance of recurrent corticocortical communication in the maintenance of consciousness and suggest a direct effect of propofol on cortical dynamics. [less ▲]Detailed reference viewed: 36 (4 ULg)
Coma and consciousness: Paradigms (re)framed by neuroimaging.
Laureys, Steven ;
in NeuroImage (2012)
The past 15years has provided an unprecedented collection of discoveries that bear upon our scientific understanding of recovery of consciousness in the human brain following severe brain damage ... [more ▼]
The past 15years has provided an unprecedented collection of discoveries that bear upon our scientific understanding of recovery of consciousness in the human brain following severe brain damage. Highlighted among these discoveries are unique demonstrations that patients with little or no behavioral evidence of conscious awareness may retain critical cognitive capacities and the first scientific demonstrations that some patients, with severely injured brains and very longstanding conditions of limited behavioral responsiveness, may nonetheless harbor latent capacities for significant recovery. Included among such capacities are particularly human functions of language and higher-level cognition that either spontaneously or through direct interventions may reemerge even at long time intervals or remain unrecognized. Collectively, these observations have reframed scientific inquiry and further led to important new insights into mechanisms underlying consciousness in the human brain. These studies support a model of consciousness as the emergent property of the collective behavior of widespread frontoparietal network connectivity modulated by specific forebrain circuit mechanisms. We here review these advances in measurement and the scientific and broader implications of this rapidly progressing field of research. [less ▲]Detailed reference viewed: 79 (4 ULg)
Coma and related disorders
Charland-Verville, Vanessa ; ; Laureys, Steven et al
in Swiss Archives of Neurology and Psychiatry (2012), 163(8), 265-272
Disorders of consciousness represent a major challenge in clinical practice. The last decade of neuroscience research brought new insights about brain function and neural correlates of these pathological ... [more ▼]
Disorders of consciousness represent a major challenge in clinical practice. The last decade of neuroscience research brought new insights about brain function and neural correlates of these pathological states of consciousness. Although behavioural evaluation still remains the gold standard, conscious behaviours are too often missed, leading to unwanted grey zones between conscious and unconscious patients. In order to increase the chances of detecting the signs of consciousness, scientists now focus on the development and validation of neuroimaging and electrophysiological paradigms in noncommunicative patients. Recent insights in this field also raise new questions of medical ethics. Indeed, for conscious patients, legal questions will occur about treatment plans, rehabilitation and communication strategies while for the unconscious patients, end-of-life decisions will take place after the patients’ condition is stated as “permanent” or “irreversible”. [less ▲]Detailed reference viewed: 47 (8 ULg)
Granger causality analysis of steady-state electroencephalographic signals during propofol-induced anaesthesia.
; ; Bruno, Marie-Aurélie et al
in PLoS ONE (2012), 7(1), 29072
Changes in conscious level have been associated with changes in dynamical integration and segregation among distributed brain regions. Recent theoretical developments emphasize changes in directed ... [more ▼]
Changes in conscious level have been associated with changes in dynamical integration and segregation among distributed brain regions. Recent theoretical developments emphasize changes in directed functional (i.e., causal) connectivity as reflected in quantities such as 'integrated information' and 'causal density'. Here we develop and illustrate a rigorous methodology for assessing causal connectivity from electroencephalographic (EEG) signals using Granger causality (GC). Our method addresses the challenges of non-stationarity and bias by dividing data into short segments and applying permutation analysis. We apply the method to EEG data obtained from subjects undergoing propofol-induced anaesthesia, with signals source-localized to the anterior and posterior cingulate cortices. We found significant increases in bidirectional GC in most subjects during loss-of-consciousness, especially in the beta and gamma frequency ranges. Corroborating a previous analysis we also found increases in synchrony in these ranges; importantly, the Granger causality analysis showed higher inter-subject consistency than the synchrony analysis. Finally, we validate our method using simulated data generated from a model for which GC values can be analytically derived. In summary, our findings advance the methodology of Granger causality analysis of EEG data and carry implications for integrated information and causal density theories of consciousness. [less ▲]Detailed reference viewed: 138 (5 ULg)
A default mode of brain function in altered states of consciousness.
; Vanhaudenhuyse, Audrey ; Boly, Mélanie et al
in Archives Italiennes de Biologie (2012), 150(2-3), 107-21
Using modern brain imaging techniques, new discoveries are being made concerning the spontaneous activity of the brain when it is devoid of attention-demanding tasks. Spatially separated patches of ... [more ▼]
Using modern brain imaging techniques, new discoveries are being made concerning the spontaneous activity of the brain when it is devoid of attention-demanding tasks. Spatially separated patches of neuronal assemblies have been found to show synchronized oscillatory activity behavior and are said to be functionally connected. One of the most robust of these is the default mode network, which is associated with intrinsic processes like mind wandering and self-projection. Furthermore, activity in this network is anticorrelated with activity in a network that is linked to attention to external stimuli. The integrity of both networks is disturbed in altered states of consciousness, like sleep, general anesthesia and hypnosis. In coma and related disorders of consciousness, encompassing the vegetative state (unresponsive wakefulness syndrome) and minimally conscious state, default mode network integrity correlates with the level of remaining consciousness, offering the possibility of using this information for diagnostic and prognostic purposes. Functional brain imaging is currently being validated as a valuable addition to the standardized behavioral assessments that are already in use. [less ▲]Detailed reference viewed: 197 (4 ULg)
Assessment of White Matter Injury and Outcome in Severe Brain Trauma: A Prospective Multicenter Cohort
; ; et al
in Anesthesiology (2012), 117(6), 1300-1310
BACKGROUND:: Existing methods to predict recovery after severe traumatic brain injury lack accuracy. The aim of this study is to determine the prognostic value of quantitative diffusion tensor imaging ... [more ▼]
BACKGROUND:: Existing methods to predict recovery after severe traumatic brain injury lack accuracy. The aim of this study is to determine the prognostic value of quantitative diffusion tensor imaging (DTI). METHODS:: In a multicenter study, the authors prospectively enrolled 105 patients who remained comatose at least 7 days after traumatic brain injury. Patients underwent brain magnetic resonance imaging, including DTI in 20 preselected white matter tracts. Patients were evaluated at 1 yr with a modified Glasgow Outcome Scale. A composite DTI score was constructed for outcome prognostication on this training database and then validated on an independent database (n = 38). DTI score was compared with the International Mission for Prognosis and Analysis of Clinical Trials Score. RESULTS:: Using the DTI score for prediction of unfavorable outcome on the training database, the area under the receiver operating characteristic curve was 0.84 (95% CI: 0.75-0.91). The DTI score had a sensitivity of 64% and a specificity of 95% for the prediction of unfavorable outcome. On the validation-independent database, the area under the receiver operating characteristic curve was 0.80 (95% CI: 0.54-0.94). On the training database, reclassification methods showed significant improvement of classification accuracy (P < 0.05) compared with the International Mission for Prognosis and Analysis of Clinical Trials score. Similar results were observed on the validation database. CONCLUSIONS:: White matter assessment with quantitative DTI increases the accuracy of long-term outcome prediction compared with the available clinical/radiographic prognostic score. [less ▲]Detailed reference viewed: 17 (2 ULg)
Connectivity graph analysis of the auditory resting state network in tinnitus.
MAUDOUX, Audrey ; Lefèbvre, Philippe ; et al
in Brain Research (2012), 1485
Thirteen chronic tinnitus patients and fifteen age-matched healthy controls were studied on a 3T magnetic resonance imaging (MRI) scanner during resting condition (i.e. eyes closed, no task performance ... [more ▼]
Thirteen chronic tinnitus patients and fifteen age-matched healthy controls were studied on a 3T magnetic resonance imaging (MRI) scanner during resting condition (i.e. eyes closed, no task performance). The auditory resting-state component was selected using an automatic component selection approach. Functional connectivity (correlations/anti-correlations) in the extracted network was portrayed by integrating the independent component analysis (ICA) approach with a graph theory method. Tinnitus and control groups showed different graph connectivity patterns. In the control group, the connectivity graph was divided into two distinct anti-correlated networks. The first one encompassed the auditory cortices and the insula. The second one encompassed frontoparietal and anterior cingulate cortices, brainstem, amygdala, basal ganglia/nucleus accumbens and parahippocampal regions. In the tinnitus group, only one of the two previously described networks was observed, encompassing the auditory cortices and the insula. Direct group comparison showed, in the tinnitus group, an increased functional connectivity between auditory cortices and the left parahippocampal region surviving multiple comparisons. We investigated a possible correlation between four tinnitus relevant measures (tinnitus handicap inventory (THI) and tinnitus questionnaire (TQ) scores, tinnitus duration and tinnitus intensity during the scanning session) and the connectivity pattern in the tinnitus population. We observed a significant positive correlation between the beta values of the posterior cingulate/precuneus region and the THI score. Our results show a modified functional connectivity pattern in tinnitus sufferers and highlight the role of the parahippocampal region in tinnitus physiopathology. They also point out the importance of the activity and connectivity pattern of the posterior cingulate cortex/precuneus region to the development of the tinnitus associated distress. This article is part of a Special Issue entitled: Tinnitus Neuroscience. [less ▲]Detailed reference viewed: 67 (9 ULg)
A sensitive scale to assess nociceptive pain in patients with disorders of consciousness.
Chatelle, Camille ; Majerus, Steve ; et al
in Journal of Neurology, Neurosurgery & Psychiatry (2012), 83(12), 1233-7
OBJECTIVE: To determine the sensitivity of the Nociception Coma Scale (NCS), the first scale developed to assess nociceptive pain in vegetative state and minimally conscious state patients, in comparing ... [more ▼]
OBJECTIVE: To determine the sensitivity of the Nociception Coma Scale (NCS), the first scale developed to assess nociceptive pain in vegetative state and minimally conscious state patients, in comparing behavioural changes in response to noxious versus non-noxious stimulation. METHODS: The NCS was administered to assess patients' responses in three conditions: (1) baseline (observation of spontaneous behaviours), (2) non-noxious/tactile stimulation (taps on the patient's shoulder), and (3) noxious stimulation (pressure on the nail bed). RESULTS: We included 64 patients (27 vegetative state and 37 minimally conscious state; age range 20-82 years; 22 traumatic brain injury; 21 in the acute stage). The NCS total scores and subscores (motor, verbal and facial) were higher for the noxious versus the non-noxious stimulation conditions. We did not observe a difference between the non-noxious and the noxious stimulation conditions for the visual subscale. We also found a NCS cut-off value of 4 differentiating the patients receiving a noxious stimulation from patients receiving a non-noxious stimulation. The exclusion of the visual subscale increased the cut-off sensitivity (from 46% to 73%; specificity of 97% and accuracy of 85%). CONCLUSION: We propose a new version of the NCS excluding the visual subscale, the NCS-R, which constitutes a highly sensitive tool to assess responses to nociceptive pain in severely brain injured patients. [less ▲]Detailed reference viewed: 27 (1 ULg)
Resting-state EEG study of comatose patients: a connectivity and frequency analysis to find differences between vegetative and minimally conscious states.
Lehembre, Remy ; Bruno, Marie-Aurélie ; Vanhaudenhuyse, Audrey et al
in Functional Neurology (2012), 27(1), 41-47
The aim of this study was to look for differences in the power spectra and in EEG connectivity measures between patients in the vegetative state (VS/UWS) and patients in the minimally conscious state (MCS ... [more ▼]
The aim of this study was to look for differences in the power spectra and in EEG connectivity measures between patients in the vegetative state (VS/UWS) and patients in the minimally conscious state (MCS). The EEG of 31 patients was recorded and analyzed. Power spectra were obtained using modern multitaper methods. Three connectivity measures (coherence, the imaginary part of coherency and the phase lag index) were computed. Of the 31 patients, 21 were diagnosed as MCS and 10 as VS/UWS using the Coma Recovery Scale-Revised (CRS-R). EEG power spectra revealed differences between the two conditions. The VS/UWS patients showed increased delta power but decreased alpha power compared with the MCS patients. Connectivity measures were correlated with the CRS-R diagnosis; patients in the VS/UWS had significantly lower connectivity than MCS patients in the theta and alpha bands. Standard EEG recorded in clinical conditions could be used as a tool to help the clinician in the diagnosis of disorders of consciousness. [less ▲]Detailed reference viewed: 360 (31 ULg)
Metabolic activity in external and internal awareness networks in severely brain-damaged patients.
Thibaut, Aurore ; Bruno, Marie-Aurélie ; Chatelle, Camille et al
in Journal of Rehabilitation Medicine (2012), 44(6), 487-94
OBJECTIVE: An extrinsic cerebral network (encompassing lateral frontoparietal cortices) related to external/sensory awareness and an intrinsic midline network related to internal/self-awareness have been ... [more ▼]
OBJECTIVE: An extrinsic cerebral network (encompassing lateral frontoparietal cortices) related to external/sensory awareness and an intrinsic midline network related to internal/self-awareness have been identified recently. This study measured brain metabolism in both networks in patients with severe brain damage. DESIGN: Prospective [18F]-fluorodeoxyglucose-positron emission tomography and Coma Recovery Scale-Revised assessments in a university hospital setting. SUBJECTS: Healthy volunteers and patients in vegetative state/unresponsive wakefulness syndrome (VS/UWS), minimally conscious state (MCS), emergence from MCS (EMCS), and locked-in syndrome (LIS). RESULTS: A total of 70 patients were included in the study: 24 VS/UWS, 28 MCS, 10 EMCS, 8 LIS and 39 age-matched controls. VS/UWS showed metabolic dysfunction in extrinsic and intrinsic networks and thalami. MCS showed dysfunction mostly in intrinsic network and thalami. EMCS showed impairment in posterior cingulate/retrosplenial cortices. LIS showed dysfunction only in infratentorial regions. Coma Recovery Scale-Revised total scores correlated with metabolic activity in both extrinsic and part of the intrinsic network and thalami. CONCLUSION: Progressive recovery of extrinsic and intrinsic awareness network activity was observed in severely brain-damaged patients, ranging from VS/UWS, MCS, EMCS to LIS. The predominance of intrinsic network impairment in MCS could reflect altered internal/self-awareness in these patients, which is difficult to quantify at the bedside. [less ▲]Detailed reference viewed: 345 (60 ULg)
Prognosis of patients with altered states of consciousness
Bruno, Marie-Aurélie ; ; Vanhaudenhuyse, Audrey et al
in Schnakers, Caroline; Laureys, Steven (Eds.) Coma and disorders of consciousness (2012)Detailed reference viewed: 109 (2 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: 24 (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: 51 (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: 38 (2 ULg)